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https://www.readbyqxmd.com/read/29034060/activation-of-the-aryl-hydrocarbon-receptor-and-risk-of-lymphoma-subtypes
#1
Sonia Sanna, Giannina Satta, Marina Padoan, Sara Piro, Angela Gambelunghe, Lucia Miligi, Giovanni Maria Ferri, Corrado Magnani, Giacomo Muzi, Luigi Rigacci, Maria Giuseppina Cabras, Emanuele Angelucci, Gian Carlo Latte, Attilio Gabbas, Maria Grazia Ennas, Pierluigi Cocco
The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay(®) and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE)...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/28988742/chimeric-antigen-receptor-t-cell-therapy-for-hematological-malignancies-and-solid-tumors-clinical-data-to-date-current-limitations-and-perspectives
#2
REVIEW
J Gauthier, I Yakoub-Agha
Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti-tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy...
October 5, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28978850/recent-topics-in-imids-and-cereblon
#3
Takumi Ito, Hiroshi Handa
Immunomodulatory drugs (IMiDs) are a new class of anticancer compounds that are derived from thalidomide. Lenalidomide and pomalidomide are well-known IMiDs, and they have already been approved by FDA for the treatment of several diseases, including multiple myeloma. Cereblon (CRBN) is a common primary target for IMiDs. It works as a substrate receptor of CRL4. Accumulating evidence has shown that the substrate specificity of CRL4(CRBN) is altered by ligands such as IMiDs. Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators"...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978241/treating-hematological-malignancies-with-cell-therapy-where-are-we-now
#4
Elisa Landoni, Barbara Savoldo
Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative 'live-drug'. Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells...
October 5, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28972539/cd56bright-nk-cells-exhibit-potent-antitumor-responses-following-il-15-priming
#5
Julia A Wagner, Maximillian Rosario, Rizwan Romee, Melissa M Berrien-Elliott, Stephanie E Schneider, Jeffrey W Leong, Ryan P Sullivan, Brea A Jewell, Michelle Becker-Hapak, Timothy Schappe, Sara Abdel-Latif, Aaron R Ireland, Devika Jaishankar, Justin A King, Ravi Vij, Dennis Clement, Jodie Goodridge, Karl-Johan Malmberg, Hing C Wong, Todd A Fehniger
NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28961609/dcone-as-an-allogeneic-cell-based-vaccine-for-multiple-myeloma
#6
Rebecca Karp Leaf, Dina Stroopinsky, Athalia R Pyzer, Ada M Kruisbeek, Sandra van Wetering, Abigail Washington, Adam Ephraim, Leandra Cole, Adam Morin, Salvia Jain, Myrna R Nahas, Arik Apel, Jon Arnason, Ayad Hamdan, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28958164/targeted-inhibition-of-human-hematological-cancers-in-vivo-by-doxorubicin-encapsulated-in-smart-lipoic-acid-crosslinked-hyaluronic-acid-nanoparticles
#7
Yinan Zhong, Fenghua Meng, Chao Deng, Xinliang Mao, Zhiyuan Zhong
The chemotherapy of hematological cancers is challenged by its poor selectivity that leads to low therapeutic efficacy and pronounced adverse effects. Here, we report that doxorubicin encapsulated in lipoic acid-crosslinked hyaluronic acid nanoparticles (LACHA-DOX) mediate highly efficacious and targeted inhibition of human hematological cancers including LP-1 human multiple myeloma (MM) and AML-2 human acute myeloid leukemia xenografted in nude mice. LACHA-DOX had a size of ca. 183 nm and a DOX loading content of ca...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28951562/a-compound-chimeric-antigen-receptor-strategy-for-targeting-multiple-myeloma
#8
K H Chen, M Wada, K G Pinz, H Liu, X Shuai, X Chen, L E Yan, J C Petrov, H Salman, L Senzel, E L H Leung, X Jiang, Y Ma
Current clinical outcomes using CARs against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen positive or negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing 2 complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1...
September 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#9
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#10
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28901387/triptolide-blocks-the-stat3-signaling-pathway-through-induction-of-protein-tyrosine-phosphatase-shp-1-in-multiple-myeloma-cells
#11
Ji-Hun Kim, Byoungduck Park
Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis...
November 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28900828/everyday-life-following-hematopoietic-stem-cell-transplantation-decline-in-physical-symptoms-within-the-first-month-and-change-related-predictors
#12
Aleksandra Kroemeke, Małgorzata Sobczyk-Kruszelnicka, Zuzanna Kwissa-Gajewska
PURPOSE: Lower quality of life, especially in the physical domain (Physical-QOL), is common in patients after hematopoietic stem cell transplantation (HSCT). However, few studies explore changes in the Physical-QOL, i.e., physical symptoms, in everyday life of patients following HSCT. The present study addresses this gap by examining patient daily physical symptoms and their predictors in terms of demographic and clinical characteristics. METHODS: Physical symptoms were reported by 188 patients (56...
September 12, 2017: Quality of Life Research
https://www.readbyqxmd.com/read/28881116/surgical-roles-for-spinal-involvement-of-hematological-malignancies
#13
Sang-Il Kim, Young-Hoon Kim, Kee-Yong Ha, Jae-Won Lee, Jin-Woo Lee
OBJECTIVE: Patients with hematological malignancies frequently encounter spine-related symptoms, which are caused by disease itself or process of treatment. However, there is still lack of knowledge on their epidemiology and clinical courses. The purpose of this article is to review clinical presentations and surgical results for spinal involvement of hematologic malignancies. METHODS: From January 2011 to September 2014, 195 patients (98 males and 97 females) suffering from hematological malignancies combined with spinal problems were retrospectively analyzed for clinical and radiological characteristics and their clinical results...
September 2017: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#14
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28862287/use-of-differential-scanning-calorimetry-and-immunoaffinity-chromatography-to-identify-disease-induced-changes-in-human-blood-plasma-proteome
#15
Sandi Brudar, Urh Černigoj, Helena Podgornik, Mojca Kržan, Iztok Prislan
Differential scanning calorimetry provides unique signatures of blood plasma samples. Plasma samples from diseased individuals yield specific thermograms, which differ from each other and from plasma samples of healthy individuals. Thermograms from individuals suffering from chronic lymphocytic leukemia, multiple myeloma and acute myeloid leukemia were measured with DSC. To obtain additional information about thermal behaviour of plasma proteins immunoaffinity chromatography was introduced. An immunoextraction of HSA using a chromatographic column with immobilized anti-HSA was carried out in order to enrich less abundant plasma proteins, which could provide a further insight into disease development...
September 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/28860655/pomalidomide-dexamethasone-in-refractory-multiple-myeloma-long-term-follow-up-of-a-multi-cohort-phase-ii-clinical-trial
#16
S Ailawadhi, J R Mikhael, B R LaPlant, K M Laumann, S Kumar, V Roy, D Dingli, P L Bergsagel, F K Buadi, S V Rajkumar, R Fonseca, M A Gertz, P Kapoor, T Sher, S R Hayman, A K Stewart, A Dispenzieri, R A Kyle, W I Gonsalves, C B Reeder, Y Lin, R S Go, N Leung, T Kourelis, J A Lust, S J Russell, A A Chanan-Khan, M Q Lacy
Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs...
September 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28852198/extracellular-vesicles-as-potential-biomarkers-of-acute-graft-vs-host-disease
#17
G Lia, L Brunello, S Bruno, A Carpanetto, P Omedè, M Festuccia, L Tosti, E Maffini, L Giaccone, M Arpinati, G Ciccone, M Boccadoro, A Evangelista, G Camussi, B Bruno
Acute Graft-vs.-Host Disease (GVHD) is a serious complication after allografting. We carried out an exploratory study to investigate a potential correlation of surface antigens on Extracellular Vesicles (EVs) and acute GVHD. EVs were extracted from serum samples from 41 multiple myeloma patients who underwent allografting. EVs were characterized by flow-cytometry using a panel of 13 antibodies against specific membrane proteins which were reported to be predictive of acute GVHD. We observed a correlation between 3 potential biomarkers expressed on EVs surface and acute GVHD onset by both logistic regression analysis and Cox proportional hazard model...
August 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28843399/valosin-containing-protein-p97-as-a-novel-therapeutic-target-in-acute-lymphoblastic-leukemia
#18
Gabriele Gugliotta, Makoto Sudo, Qi Cao, De-Chen Lin, Haibo Sun, Sumiko Takao, Ronan Le Moigne, Mark Rolfe, Sigal Gery, Markus Müschen, Michele Cavo, H Phillip Koeffler
B acute lymphoblastic leukemia (B-ALL) cells are distinctively vulnerable to endoplasmic reticulum (ER) stress. Recently, inhibition of p97 was shown to induce ER stress and subsequently cell death in solid tumors and in multiple myeloma. We investigated the role of a novel, orally available, p97 inhibitor (CB-5083; Cleave Biosciences) in B-ALL. CB-5083 induced a significant reduction in viability in 10 human B-ALL cell lines, harboring the most common fusion-genes involved in pediatric and adult B-ALL, with IC50s ranging from 0...
October 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28832023/oncolytic-reovirus-sensitizes-multiple-myeloma-cells-to-anti-pd-l1-therapy
#19
K R Kelly, C M Espitia, W Zhao, K Wu, V Visconte, F Anwer, C M Calton, J S Carew, S T Nawrocki
No abstract text is available yet for this article.
August 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28792782/emerging-antibody-drug-conjugates-for-treating-lymphoid-malignancies
#20
REVIEW
Anna Wolska-Washer, Pawel Robak, Piotr Smolewski, Tadeusz Robak
Antibody-drug conjugates (ADC) are monoclonal antibodies (Mabs) attached to biologically active drugs through specialized chemical linkers. They deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. These agents should improve the potency of chemotherapy by increasing the accumulation of cytotoxic the drug within or near the neoplastic cells with reduced systemic effects. Areas covered: A literature review was conducted of the MEDLINE database PubMed for articles in English examining Mabs, B-cell receptor pathway inhibitors and immunomodulating drugs...
September 2017: Expert Opinion on Emerging Drugs
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