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https://www.readbyqxmd.com/read/28806151/establishment-of-a-monoclonal-antibody-against-chgilz
#1
Zhiyuan He, Yongqiang Wang
The chicken glucocorticoid-induced leucine zipper (chGILZ) participates in the inflammation of avian immunosuppressive diseases. We aimed to establish a monoclonal antibody (MAb) against chGILZ and to investigate its distribution in clinical diagnosis. A gene cloned from chicken embryo fibroblast (CEF) cell was inserted into the expression vector pET-28a and pGEX-6p-1. The recombinant expression vectors were transformed into Escherichia coli BL21 (DE3). Then the recombinant proteins His-chGILZ and GST-chGILZ were successfully expressed and purified...
August 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28744319/-177-lu-pentixather-comprehensive-preclinical-characterization-of-a-first-cxcr4-directed-endoradiotherapeutic-agent
#2
Margret Schottelius, Theresa Osl, Andreas Poschenrieder, Frauke Hoffmann, Seval Beykan, Heribert Hänscheid, Andreas Schirbel, Andreas K Buck, Saskia Kropf, Markus Schwaiger, Ulrich Keller, Michael Lassmann, Hans-Jürgen Wester
Purpose: Based on the clinical relevance of the chemokine receptor 4 (CXCR4) as a molecular target in cancer and on the success of [(68)Ga]pentixafor as an imaging probe for high-contrast visualization of CXCR4-expression, the spectrum of clinical CXCR4-targeting was expanded towards peptide receptor radionuclide therapy (PRRT) by the development of [(177)Lu]pentixather. Experimental design: CXCR4 affinity, binding specificity, hCXCR4 selectivity and internalization efficiency of [(177)Lu]pentixather were evaluated using different human and murine cancer cell lines...
2017: Theranostics
https://www.readbyqxmd.com/read/28724539/racial-and-ethnic-disparities-in-hematologic-malignancies
#3
Kedar Kirtane, Stephanie J Lee
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28719245/production-of-a-mouse-monoclonal-antibody-against-mortalin-by-whole-cell-immunization
#4
Marzieh Rezaei, Abbas Ghaderi
Pancreatic carcinoma is the fourth leading cause of cancer death and is characterized by early invasion and metastasis. Advances in molecular biology directed new strategies in targeted therapy using monoclonal antibodies. To identify new biomarkers, we generated a panel of monoclonal antibodies against the newly established cell line, Faraz-ICR, from a patient with acinar cell carcinoma. After immunization of BALB/c female mice with Faraz-ICR cell line and fusion of splenocytes with SP2/0 myeloma cell line, high reactive hybridoma producing antibodies to Faraz-ICR were detected using enzyme-linked immunosorbent assay, immunofluorescence staining and flow cytometry...
August 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28718729/the-novel-autophagy-inhibitor-elaiophylin-exerts-antitumor-activity-against-multiple-myeloma-with-mutant-tp53-in-part-through-endoplasmic-reticulum-stress-induced-apoptosis
#5
Gaoxiang Wang, Pan Zhou, Xing Chen, Lei Zhao, Jiaqi Tan, Yang Yang, Yong Fang, Jianfeng Zhou
Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biologic effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest...
July 18, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28693796/regulatory-effects-of-berberine-on-micrornome-in-cancer-and-other-conditions
#6
REVIEW
Seyed Hasan Ayati, Badrieh Fazeli, Amir Abbas Momtazi-Borojeni, Arrigo F G Cicero, Matteo Pirro, Amirhossein Sahebkar
Berberine (BBR) is an isoquinoline alkaloid found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial, antiparasitic and fungicide activities. Multiple pharmacological actions of BBR stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are single-stranded, evolutionary conserved, small non-coding RNA molecules with a length of 19-23 nucleotides that are involved in RNA silencing and post-transcriptional regulation of gene expression through binding to the 3'-untranslated region (3'UTR) of target mRNA...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28671297/standardisation-of-minimal-residual-disease-in-multiple-myeloma
#7
V Innao, A Allegra, S Russo, D Gerace, D Vaddinelli, A Alonci, A G Allegra, C Musolino
The assessment of the effectiveness of chemotherapy in oncology cannot disregard the concept of minimal residual disease (MRD). In fact, the efforts of numerous scientific groups all over the world are currently focusing on this issue, with the sole purpose of defining sensitive, effective assessment criteria that are, above all, able to give acceptable, easily repeatable results worldwide. Regarding this issue, especially with the advent of new drugs, multiple myeloma is one of the haematologic malignancies for which a consensus has not yet been reached...
July 3, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28655090/-molecular-mechanisms-and-relationship-of-m2-polarized-macrophages-with-early-response-in-multiple-myeloma
#8
X Y Chen, R X Sun, W Y Zhang, T Liu, Y H Zheng, Y Wu
Objective: To investigate the relationship between M2-polarized macrophages and early response in multiple myeloma and its molecular mechanism. Methods: Two hundred and forty bone marrow biopsy tissue were collected and M2-polarized macrophages were stained by anti-CD163 monoclonal antibody. In vitro M2-polarized macrophages were derived from human peripheral blood mononuclear cell or THP-1 cells and identified by flow cytometry. Two myeloma cell lines RPMI 8226 and U266 were co-cultured with M2 macrophages using a transwell system...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28642592/integrative-network-analysis-identifies-novel-drivers-of-pathogenesis-and-progression-in-newly-diagnosed-multiple-myeloma
#9
A Laganà, D Perumal, D Melnekoff, B Readhead, B A Kidd, V Leshchenko, P-Y Kuo, J Keats, M DeRome, J Yesil, D Auclair, S Lonial, A Chari, H J Cho, B Barlogie, S Jagannath, J T Dudley, S Parekh
Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells characterized by wide clinical and molecular heterogeneity. In this study we applied an integrative network biology approach to molecular and clinical data measured from 450 patients with newly diagnosed MM from the MMRF (Multiple Myeloma Research Foundation) CoMMpass study. A novel network model of myeloma (MMNet) was constructed, revealing complex molecular disease patterns and novel associations between clinical traits and genomic markers...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28592764/multiple-myeloma-pathophysiology-and-progress-in-management
#10
Junya Kuroda, Yoshiaki Chinen
There have been dramatic recent advances in understanding the basic pathophysiology and treatment strategies for multiple myeloma (MM). Research has shown both a high inter-patient diversity and intra-clonal heterogeneity even in a single patient in terms of cytogenetic/molecular abnormalities, and has also identified marked diversity in the immunological factors involved in tumor surveillance among MM patients. In the presence of a variety of novel agents, including molecular-targeted agents, immunomodulatory agents, and monoclonal antibodies, the optimal translation of current knowledge on both molecular and immunologic findings into clinical use is crucial for managing MM...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1-905-trial-patients
#11
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28573897/molecular-mechanisms-current-management-and-next-generation-therapy-in-myeloma-bone-disease
#12
Roy Heusschen, Joséphine Muller, Elodie Duray, Nadia Withofs, Arnold Bolomsky, Frédéric Baron, Yves Beguin, Eline Menu, Heinz Ludwig, Jo Caers
Multiple myeloma (MM) bone disease is a major cause of morbidity and mortality in MM patients and persists even in patients in remission. This bone disease is caused by an uncoupling of bone remodeling, with increased osteoclast and decreased osteoblast activity and formation, culminating in lytic bone destruction. Bisphosphonates are the current standard of care but new therapies are needed. As the molecular mechanisms controlling MM bone disease are increasingly well understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds now show promising results...
June 2, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28550183/somatic-mutation-spectrum-in-monoclonal-gammopathy-of-undetermined-significance-indicates-a-less-complex-genomic-landscape-compared-to-multiple-myeloma
#13
Aneta Mikulasova, Christopher P Wardell, Alexander Murison, Eileen M Boyle, Graham H Jackson, Jan Smetana, Zuzana Kufova, Ludek Pour, Viera Sandecka, Martina Almasi, Pavla Vsianska, Evzen Gregora, Petr Kuglik, Roman Hajek, Faith E Davies, Gareth J Morgan, Brian A Walker
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28549851/identification-of-pathway-based-prognostic-gene-signatures-in-patients-with-multiple-myeloma
#14
Mohamad Zamani-Ahmadmahmudi, Shahreyar Dabiri, Nadia Nadimi
Molecular profiling is used to extract prognostic gene signatures in different cancers such as multiple myeloma (MM), which is the second most common hematological malignancy. In this study, we utilized gene expression profiles to find biological pathways that could efficiently predict survival time in patients with MM. Four data sets-namely GSE2658 (559 samples), GSE9782 (264 samples), GSE6477 (147 samples), and GSE57317 (55 samples)-were employed. GSE2658 was used as a training data set and the others as validation data sets...
May 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28548370/current-state-of-a-dual-behavior-of-antimicrobial-peptides-therapeutic-agents-and-promising-delivery-vectors
#15
REVIEW
Urszula Piotrowska, Marcin Sobczak, Ewa Oledzka
Microorganism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties...
May 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28522584/cooperative-targets-of-combined-mtor-hdac-inhibition-promote-myc-degradation
#16
John K Simmons, Aleksandra M Michalowski, Benjamin J Gamache, Wendy DuBois, Jyoti Patel, Ke Zhang, Joy Gary, Shuling Zhang, Snehal Gaikwad, Daniel Connors, Nicholas Watson, Elena Leon, Jin-Qiu Chen, W Michael Kuehl, Maxwell P Lee, Adriana Zingone, Ola Landgren, Peter Ordentlich, Jing Huang, Beverly A Mock
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents.  In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522572/the-prognostic-value-of-the-depth-of-response-in-multiple-myeloma-depends-on-the-time-of-assessment-risk-status-and-molecular-subtype
#17
LETTER
Carolina Schinke, Antje Hoering, Hongwei Wang, Victoria Carlton, Sharmilan Thanandrarajan, Shayu Deshpande, Purvi Patel, Gabor Molnar, Sandra Susanibar, Meera Mohan, Pankaj Mathur, Muthukumar Radhakrishnan, Shadiqul Hoque, Jorge Jo Kamimoto, Monica Grazziutti, Frits van Rhee, Maurizio Zangari, Giovanni Insuasti-Beltran, Daisy Alapat, Ginell Post, Shmuel Yaccoby, Joshua Epstein, Leo Rasche, Sarah Johnson, Martin Moorhead, Tom Willis, Bart Barlogie, Brian Walker, Niels Weinhold, Faith E Davies, Gareth J Morgan
No abstract text is available yet for this article.
August 2017: Haematologica
https://www.readbyqxmd.com/read/28504689/molecular-signaling-in-multiple-myeloma-association-of-ras-raf-mutations-and-mek-erk-pathway-activation
#18
J Xu, N Pfarr, V Endris, E K Mai, N H Md Hanafiah, N Lehners, R Penzel, W Weichert, A D Ho, P Schirmacher, H Goldschmidt, M Andrulis, M S Raab
Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be incurable in most cases. A dominant mutation cluster has been identified in RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK signaling as a therapeutic target. As yet, however, the clinical relevance of this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK pathway activation by both targeted sequencing and phospho-ERK immunohistochemistry in 180 tissue biopsies from 103 patients with newly diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM)...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504647/identification-of-a-nucleoside-analog-active-against-adenosine-kinase-expressing-plasma-cell-malignancies
#19
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...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28492226/circulating-tumour-dna-sequence-analysis-as-an-alternative-to-multiple-myeloma-bone-marrow-aspirates
#20
Olena Kis, Rayan Kaedbey, Signy Chow, Arnavaz Danesh, Mark Dowar, Tiantian Li, Zhihua Li, Jessica Liu, Mark Mansour, Esther Masih-Khan, Tong Zhang, Scott V Bratman, Amit M Oza, Suzanne Kamel-Reid, Suzanne Trudel, Trevor J Pugh
The requirement for bone-marrow aspirates for genomic profiling of multiple myeloma poses an obstacle to enrolment and retention of patients in clinical trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is comparable to molecular profiling of myeloma using bone-marrow tumour cells. We report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64 cfDNA specimens from 53 myeloma patients to >20,000 × median coverage...
May 11, 2017: Nature Communications
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