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https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#1
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29882166/co-fuse-a-new-class-discovery-analysis-tool-to-identify-and-prioritize-recurrent-fusion-genes-from-rna-sequencing-data
#2
Sakrapee Paisitkriangkrai, Kelly Quek, Eva Nievergall, Anissa Jabbour, Andrew Zannettino, Chung Hoow Kok
Recurrent oncogenic fusion genes play a critical role in the development of various cancers and diseases and provide, in some cases, excellent therapeutic targets. To date, analysis tools that can identify and compare recurrent fusion genes across multiple samples have not been available to researchers. To address this deficiency, we developed Co-occurrence Fusion (Co-fuse), a new and easy to use software tool that enables biologists to merge RNA-seq information, allowing them to identify recurrent fusion genes, without the need for exhaustive data processing...
June 7, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29880611/impaired-mitochondrial-activity-explains-platelet-dysfunction-in-thrombocytopenic-cancer-patients-undergoing-chemotherapy
#3
Constance C F M J Baaten, Floor C J I Moenen, Yvonne M C Henskens, Frauke Swieringa, Rick J H Wetzels, René van Oerle, Harry F G Heijnen, Hugo Ten Cate, Graham P Holloway, Erik A M Beckers, Johan W M Heemskerk, Paola E J van der Meijden
Severe thrombocytopenia (≤50x109 platelets/L) due to hematological malignancy and intensive chemotherapy is associated with an increased risk of clinically significant bleeding. Since the bleeding risk is not linked to the platelet count only, other hemostatic factors must be involved. In 77 patients with acute leukemia, multiple myeloma or malignant lymphoma, who experienced chemotherapy-induced thrombocytopenia, we studied platelet function. Platelets from all patients - independent of disease or treatment type - were to a variable extent compromised in Ca2+ flux, integrin αIIbβ3 activation and P-selectin expression, when stimulated with a panel of agonists...
June 7, 2018: Haematologica
https://www.readbyqxmd.com/read/29849629/multiple-myeloma-of-the-central-nervous-system-13-cases-and-review-of-the-literature
#4
REVIEW
Gergely Varga, Gábor Mikala, László Gopcsa, Zoltán Csukly, Sarolta Kollai, György Balázs, Tímár Botond, Nikolett Wohner, Laura Horváth, Gergely Szombath, Péter Farkas, Tamás Masszi
Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment...
2018: Journal of Oncology
https://www.readbyqxmd.com/read/29848505/kidney-involvement-of-patients-with-waldenstr%C3%A3-m-macroglobulinemia-and-other-igm-producing-b-cell-lymphoproliferative-disorders
#5
Larissa Higgins, Samih H Nasr, Samar M Said, Prashant Kapoor, David Dingli, Rebecca L King, S Vincent Rajkumar, Robert A Kyle, Taxiarchis Kourelis, Morie A Gertz, Angela Dispenzieri, Martha Q Lacy, Francis K Buadi, Stephen M Ansell, Wilson I Gonsalves, Carrie A Thompson, Fernando C Fervenza, Ladan Zand, Yi L Hwa, Dragan Jevremovic, Min Shi, Nelson Leung
BACKGROUND AND OBJECTIVES: Kidney involvement in Waldenström macroglobulinemia is less well described compared with kidney manifestations in multiple myeloma. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Of the 1363 patients seen with Waldenström macroglobulinemia and other IgM-secreting B cell lymphoproliferative disorders seen at the Mayo Clinic between 1996 and 2015, 57 kidney biopsies were retrospectively studied. The biopsy findings were correlated with clinical, kidney, and hematologic characteristics...
May 30, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29847570/feasibility-of-controlling-cd38-car-t-cell-activity-with-a-tet-on-inducible-car-design
#6
Esther Drent, Renée Poels, Manon J Mulders, Niels W C J van de Donk, Maria Themeli, Henk M Lokhorst, Tuna Mutis
Recent clinical advances with chimeric antigen receptor (CAR) T cells have led to the accelerated clinical approval of CD19-CARs to treat acute lymphoblastic leukemia. The CAR T cell therapy is nevertheless associated with toxicities, especially if the CARs are not entirely tumor-specific. Therefore, strategies for controlling the CAR T cell activity are required to improve their safety profile. Here, by using the multiple myeloma (MM)-associated CD38 molecule as target molecule, we tested the feasibility and utility of a doxycycline (DOX) inducible Tet-on CD38-CAR design to control the off-target toxicities of CAR T cells...
2018: PloS One
https://www.readbyqxmd.com/read/29805699/a-predicting-model-of-bone-marrow-malignant-infiltration-in-18-f-fdg-pet-ct-images-with-increased-diffuse-bone-marrow-fdg-uptake
#7
Mingge Zhou, Yumei Chen, Jianjun Liu, Gang Huang
Purpose: To demonstrate the relationship between the etiologies of increased diffuse bone marrow (BM) 18 F-FDG uptake and PET/CT imaging/clinical features, as well as to explore a predicting model of BM malignant infiltration (MI) based on decision tree. Methods: 84 patients with increased diffuse BM uptake were retrospectively enrolled. Their complete case record and PET/CT images were reviewed, with the maximal standardized uptake values of bone marrow (SUVmaxBM) and other imaging/clinical features were noted...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29804872/investigational-antibody-drug-conjugates-for-treatment-of-b-lineage-malignancies
#8
REVIEW
Alex F Herrera, Arturo Molina
Antibody-drug conjugates (ADCs) are tripartite molecules consisting of a monoclonal antibody, a covalent linker, and a cytotoxic payload. ADC development has aimed to target the specificity inherent in antigen-antibody interactions to deliver potent cytotoxins preferentially to tumor cells and maximize antitumor activity and simultaneously minimize off-target toxicity. The earliest ADCs provided disappointing results in the clinic; however, the lessons learned regarding the need for human or humanized antibodies, more stable linkers, and greater potency payloads led to improved ADCs...
May 10, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29802118/dis3-isoforms-vary-in-their-endoribonuclease-activity-and-are-differentially-expressed-within-haematological-cancers
#9
Sophie R Robinson, Sandra C Viegas, Rute G Matos, Susana Domingues, Marisa Bedir, Helen J S Stewart, Timothy J Chevassut, Antony W Oliver, Cecilia M Arraiano, Sarah F Newbury
DIS3 is the catalytic subunit of the exosome, a protein complex involved in the 3' to 5' degradation of RNAs. DIS3 is a highly conserved exoribonuclease, also known as Rrp44. Global sequencing studies have identified DIS3 as being mutated in a range of cancers, with a considerable incidence in multiple myeloma. In this work, we have identified two protein-coding isoforms of DIS3. Both isoforms are functionally relevant and result from alternative splicing. They differ from each other in the size of their N-terminal PIN domain, which has been shown to have endoribonuclease activity and tether DIS3 to the exosome...
May 25, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29799330/greater-spending-associated-with-improved-survival-for-some-cancers-in-ocm-defined-episodes
#10
James Baumgardner, Ahva Shahabi, Mark Linthicum, Seanna Vine, Christopher Zacker, Darius Lakdawalla
BACKGROUND: Previous research finds significant variation in spending and utilization across regions, with little evidence of differences in outcomes. While such findings have been interpreted as evidence that spending can be reduced without compromising patient outcomes, the link between spending variation and outcomes remains a critical question. OBJECTIVE: To use evidence from geographic variations in spending and an individual-level survival analysis to test whether spending within oncology care episodes is associated with survival, where episodes are defined as in the Center for Medicare and Medicaid Innovation's Oncology Care Model (OCM)...
June 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29795433/prevention-and-treatment-of-relapse-after-stem-cell-transplantation-in-lymphoid-malignancies
#11
Anna Sureda, Peter Dreger, Michael R Bishop, Nicolaus Kroger, David L Porter
Relapse is now the major cause of treatment failure after allogeneic HSCT (alloHSCT). Many novel strategies to address this critical issue are now being developed and tested. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg, Germany in November 2016, international experts presented and discussed recent developments in the field. Some approaches may be applicable to a wide range of patients after transplant, whereas some may be very disease-specific. We present a report from the session dedicated to issues related to prevention and treatment of relapse of lymphoid malignancies after alloHSCT...
May 24, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29793418/clinical-studies-with-bismuth-213-and-actinium-225-for-hematologic-malignancies
#12
Joseph G Jurcic
Because α-particles have a shorter range and a higher linear energy transfer compared to β-particles, targeted α-particle therapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of α-particle therapy for acute myeloid leukemia (AML) have focused on targeting the cell surface antigen CD33 using the humanized monoclonal antibody lintuzumab. An initial phase I study showed the safety feasibility, and anti-leukemic effects of bismuth-213 (213Bi)-labeled lintuzumab...
May 24, 2018: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29787442/epidemiology-of-late-health-effects-in-ukrainian-chornobyl-cleanup-workers
#13
Dimitry Bazyka, Anatoly Prysyazhnyuk, Natalya Gudzenko, Iryna Dyagil, David Belyi, Vadim Chumak, Volodymyr Buzunov
This article summarizes the results of 30 y of follow-up of cancer and noncancer effects in Ukrainian cleanup workers after the Chornobyl accident. The number of power plant employees and first responders with acute radiation syndrome under follow-up by the National Research Center for Radiation Medicine decreased from 179 in 1986-1991 to 105 in 2011-2015. Cancers and leukemia (19) and cardiovascular diseases (21) were the main causes of deaths among acute radiation syndrome survivors (54) during the postaccident period...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#14
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29780393/immunomodulatory-drugs-exert-anti-leukemia-effects-in-acute-myeloid-leukemia-by-direct-and-immunostimulatory-activities
#15
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29777009/feasibility-of-cxcr4-directed-radioligand-therapy-in-advanced-diffuse-large-b-cell-lymphoma
#16
Constantin Lapa, Heribert Hänscheid, Malte Kircher, Andreas Schirbel, Gerd Wunderlich, Rudolf Werner, Samuel Samnick, Jörg Kotzerke, Hermann Einsele, Andreas Buck, Hans-Jürgen Wester, Götz Ulrich Grigoleit
We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29773172/seleno-l-methionine-and-l-ascorbic-acid-differentiate-the-biological-activity-of-doxorubicin-and-its-metal-complexes-as-a-new-anticancer-drugs-candidate
#17
Marzena Matejczyk, Grzegorz Świderski, Renata Świsłocka, Stanisław Józef Rosochacki, Włodzimierz Lewandowski
The most important problems of anti-cancer therapy include the toxicity of the drugs applied to healthy cells and the multi-drug cells resistance to chemotherapeutics. One of the most commonly used anticancer drugs is doxorubicin (DOX) used to treat certain leukemias and non-Hodgkin's lymphomas, as well as bladder, breast, stomach, lung, ovarian, thyroid, multiple myeloma and other cancers. Preliminary studies showed that metal complex with DOX improve its cytostatic activity with changes in their molecular structure and distribution of electrons, resulting in a substantial change of its biological activity (including antitumor activity)...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29768934/a-safety-profile-of-medications-used-to-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#18
Ramón García-Sanz, Cristina Jiménez, Verónica González de la Calle, María Eugenia Sarasquete
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the BTK inhibitors. Areas covered. Two main therapeutic attitudes are possible: 1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies, or; 2) new approaches with BTK inhibitors, usually alone...
May 17, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29743861/-pinus-roxburghii-essential-oil-anticancer-activity-and-chemical-composition-evaluation
#19
Arfaa Sajid, Qaisar Manzoor, Munawar Iqbal, Amit Kumar Tyagi, Raja Adil Sarfraz, Anam Sajid
The present study was conducted to appraise the anticancer activity of Pinus roxburghii essential oil along with chemical composition evaluation. MTT assay revealed cytotoxicity induction in colon, leukemia, multiple myeloma, pancreatic, head and neck and lung cancer cells exposed to essential oil. Cancer cell death was also observed through live/dead cell viability assay and FACS analysis. Apoptosis induced by essential oil was confirmed by cleavage of PARP and caspase-3 that suppressed the colony-forming ability of tumor cells and 50 % inhibition occurred at a dose of 25 μg/mL...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29738549/effect-of-combining-glucocorticoids-with-compound-a-on-glucocorticoid-receptor-responsiveness-in-lymphoid-malignancies
#20
Dorien Clarisse, Karlien Van Wesemael, Jan Tavernier, Fritz Offner, Ilse M Beck, Karolien De Bosscher
Glucocorticoids (GCs) are a cornerstone in the treatment of lymphoid malignancies such as multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Yet, prolonged GC use is hampered by deleterious GC-related side effects and the emergence of GC resistance. To tackle and overcome these GC-related problems, the applicability of selective glucocorticoid receptor agonists and modulators was studied, in search of fewer side-effects and at least equal therapeutic efficacy as classic GCs. Compound A (CpdA) is a prototypical example of such a selective glucocorticoid receptor modulator and does not support GR-mediated transactivation...
2018: PloS One
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