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multiples myeloma

Kerim Sonmezoglu, Betul Vatankulu, Tugrul Elverdi, Resit Akyel, Melih E Erkan, Metin Halac, Meltem Ocak, Emre Demirci, Yildiz Aydin
OBJECTIVE: In this observational pilot study, we aimed to evaluate the role of gallium-68-labelled DOTA-TATE (Ga-TATE) PET/computed tomography (CT) scanning in patients with multiple myeloma (MM), considering previous promising results obtained from conventional somatostatin receptor scintigraphy with In pentetreotide. MATERIALS AND METHODS: Twenty-one patients with a diagnosis of MM were prospectively included in this study: eight patients were referred for initial staging and 13 patients for restaging purpose...
October 21, 2016: Nuclear Medicine Communications
N Ben Abdejlil, D Belloumi, M Mâammar, R El Fatimi, L Torjman, A Lakhal, F Jenhani, S Hmida, T Ben Othman, S Ladeb
This study compared retrospectively the effectiveness, toxicity and hematopoietic recovery after autologous peripheral blood stem cell transplantation (ASCT) of two consecutive peripheral blood stem cell mobilization regimens in newly diagnosed MM patients. Patients in group 1 (n=178) were treated with 4 g/m(2) of cyclophosphamide (CY) plus G-CSF (5 μg/kg/day). Patients in group 2 (n=117) with 750 mg/m(2) of VP16 plus G-CSF (10 μg/kg/day). Optimal mobilization, defined by a target number of 8 × 10(6) CD34+ cells/kg collected, was achieved in 62...
October 24, 2016: Bone Marrow Transplantation
Salvador Alonso, Daniela Hernandez, Yu-Ting Chang, Christian D Gocke, Megan McCray, Ravi Varadhan, William H Matsui, Richard J Jones, Gabriel Ghiaur
Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in bortezomib (BTZ) resistance. However, the mechanisms involved in these interactions are not completely understood. We previously showed that expression of CYP26 in BM stromal cells maintains a retinoic acid-low (RA-low) microenvironment that prevents the differentiation of normal and malignant hematopoietic cells. Since a low secretory B cell phenotype is associated with BTZ resistance in MM and retinoid signaling promotes plasma cell differentiation and Ig production, we investigated whether stromal expression of the cytochrome P450 monooxygenase CYP26 modulates BTZ sensitivity in the BM niche...
October 24, 2016: Journal of Clinical Investigation
H van Andel, K A Kocemba, A de Haan-Kramer, C H Mellink, M Piwowar, A Broijl, M van Duin, P Sonneveld, M M Maurice, M J Kersten, M Spaargaren, S T Pals
Deletion or mutation of the gene encoding the deubiquitinating enzyme CYLD is a common genomic aberration in multiple myeloma (MM). However, the functional consequence of CYLD loss and the mechanism underlying its putative role as a tumor suppressor gene in the pathogenesis of MM has not been established. Here, we show that CYLD expression is highly variable in myeloma cell lines and primary MMs and that low CYLD expression is associated with disease progression from monoclonal gammopathy of undetermined significance to MM, and with poor overall and progression free-survival of MM patients...
October 24, 2016: Oncogene
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hoon Koon Teoh, Pei Pei Chong, Maha Abdullah, Zamberi Sekawi, Geok Chin Tan, Chooi Fun Leong, Soon Keng Cheong
No abstract text is available yet for this article.
February 2016: Pathology
Jin Roh, Keunok Jung, A-Neum Lee, Yeon Mee Kim, Jooryung Huh, Inhak Choi, Chan-Sik Park
No abstract text is available yet for this article.
February 2016: Pathology
Aaron S Rosenberg, Robin Ruthazer, Jessica K Paulus, David M Kent, Andrew M Evens, Andreas K Klein
BACKGROUND: Multiple myeloma/plasmacytoma-like posttransplantation lymphoproliferative disorder (PTLD-MM) is a rare complication of solid organ transplantation. Case series have shown variable outcomes, and survival data in the modern era are lacking. PATIENTS AND METHODS: A cohort of 212 PTLD-MM patients was identified in the Scientific Registry of Transplant Recipients between 1999 and 2011. Overall survival (OS) was estimated by the Kaplan-Meier method, and the effects of treatment and patient characteristics on OS were evaluated by Cox proportional hazards models...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
K Rakul Nambiar, Sreejith G Nair, Sherin P Mathew
No abstract text is available yet for this article.
October 19, 2016: Journal of the Egyptian National Cancer Institute
Ryan P Wurz, Christine Sastri, Derin C D'Amico, Brad Herberich, Claire L M Jackson, Liping H Pettus, Andrew S Tasker, Bin Wu, Nadia Guerrero, J Russell Lipford, Jeffrey T Winston, Yajing Yang, Paul Wang, Yen Nguyen, Kristin L Andrews, Xin Huang, Matthew R Lee, Christopher Mohr, J D Zhang, Darren L Reid, Yang Xu, Yihong Zhou, Hui-Ling Wang
High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0...
October 1, 2016: Bioorganic & Medicinal Chemistry Letters
Elizabeth Bilotti, David H Vesole, Laura McBride, Linda Schmidt, Zhijie Gao, Madiha Gilani, Ann McNeill, Urszula Bednarz, Joshua Richter, Anthony Mato, Thorsten Graef, David S Siegel
BACKGROUND: This is a retrospective chart review to evaluate the efficacy of the addition of vorinostat to lenalidomide and dexamethasone in patients with multiple myeloma relapsed/refractory to lenalidomide and dexamethasone. METHODS: Charts from 26 consecutive patients able to obtain commercial vorinostat were analyzed for response and safety data. RESULTS: The overall response rate was 31%, and the clinical beneficial rate was 50%. The median duration of response was 3 months, and the median overall survival was 28...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Yun Liang, Xin He, Xian Li, Xuzhao Zhang, Xiaohong Zhang, Lei Zhang, Xi Qiu, Xiaoying Zhao, Rongzhen Xu
Multiple myeloma (MM) remains incurable despite the development and the use of new agents. In our studies, we found that 4-chlorbenzoyl berbamine (BBMD9), a novel synthetic derivative of berbamine, inhibited the proliferation of MM cells in dose- and time-dependent manners. Flow cytometric (FCM) analysis revealed that MM cells were arrested in the G1 phase and that apoptotic cells increased in a time-dependent manner. Moreover, the BBMD9 treatment downregulated IKKα and IKKβ, inhibited p-IκBα, and blocked p65 nuclear localization...
October 21, 2016: Cancer Investigation
B Lipe, R Vukas, J Mikhael
Multiple myeloma is the second most common type of blood cancer and remains incurable despite advances in therapy. Current therapy for multiple myeloma includes a phased-approach, often consisting of initial induction therapy, consolidation and maintenance therapy. With an ever-growing landscape of treatment options, the approach to optimal therapy has become increasingly complex. Specifically, controversy surrounds the optimal use and duration of maintenance therapy. We conducted a comprehensive literature search to analyze the most current literature and to provide recommendations for maintenance therapy in multiple myeloma...
October 21, 2016: Blood Cancer Journal
A Ravindran, A C Bartley, S J Holton, W I Gonsalves, P Kapoor, M A Siddiqui, S K Hashmi, A L Marshall, A A Ashrani, A Dispenzieri, R A Kyle, S V Rajkumar, R S Go
No abstract text is available yet for this article.
October 21, 2016: Blood Cancer Journal
Ágnes Márk, Gergely Varga, Botond Timár, Csilla Kriston, Orsolya Szabó, Linda Deák, András Matolcsy, Gábor Barna
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells (PCs) in the bone marrow and other tissues. Although there are several new therapies, MM remains fatal. The interaction between MM cells and the bone marrow microenvironment promotes drug resistance and cancer cells survival. In our present work, we compared the antigen expression pattern of normal and pathological PCs and investigated the possible connections between various surface receptors, adhesion molecules, and recurrent genetic aberrations...
October 21, 2016: Hematological Oncology
Arash Latifoltojar, Margaret Hall-Craggs, Neil Rabin, Rakesh Popat, Alan Bainbridge, Nikolaos Dikaios, Magdalena Sokolska, Ali Rismani, Shirley D'Sa, Shonit Punwani, Kwee Yong
Cross-sectional imaging techniques are being increasingly used for disease evaluation in patients with multiple myeloma. Whole body magnetic resonance imaging (WB-MRI) scanning is superior to plain radiography in baseline assessment of patients but changes following treatment have not been systematically explored. We carried out paired WB-MRI scans in 21 newly diagnosed patients prior to, and 8-weeks after, starting chemotherapy, and analysed stringently selected focal lesions (FLs) for parametric changes. A total of 323 FLs were evaluated, median 20 per patient...
October 21, 2016: British Journal of Haematology
Silvia Mangiacavalli, A Pompa, V Ferretti, C Klersy, F Cocito, M Varettoni, C S Cartia, M Cazzola, A Corso
Extramedullary relapse (EMR) represents a poor prognostic marker in the course of multiple myeloma (MM). We reviewed data from 329 patients, diagnosed between 2000 and 2010, without extramedullary disease at onset to explore possible risk factors for EMR. The median overall survival of our study cohort was 6.4 years. The risk of EMR was 28 % with a median time from diagnosis to first EMR of 2.2 years (0.2-9.1 years). Patients with soft tissue masses located in extra-osseous organs (EMR-S) showed the worst outcome, compared to those with tumor masses arising from adjacent bone (EMR-B) (median OS 1...
October 21, 2016: Annals of Hematology
Sara Zahedi, Karim Shamsasenjan, Aliakbar Movassaghpour, Parvin Akbarzadehlaleh
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy...
September 2016: Advanced Pharmaceutical Bulletin
Nicola Stefano Fracchiolla, Claudio Annaloro, Francesca Guidotti, Bruno Fattizzo, Agostino Cortelezzi
Dioxin exposure and its effect on hematopoiesis and cancer have been largely investigated in both human and non-human settings. Here we systematically reviewed literature to address the question of what we know about TCDD biology and exposure. Most effects are due to TCDD interaction with a receptor of xenobiotics called AHR, which is ubiquitously represented and also works on hematopoietic myeloid and lymphoid stem cells, inducing proliferation and stem cell release from bone marrow to peripheral circulation...
October 17, 2016: Toxicology
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