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Ying Yu Liang, Ilse Schwarzinger, Ingrid Simonitsch-Klupp, Hermine Agis, Rudolf Oehler
Efficient clearance of apoptotic cells by efferocytosis is important for tissue homeostasis. Impaired efferocytosis leads to the accumulation of cell debris, which is regarded as a trigger in chronic inflammation and autoimmune diseases. Patients with hematological neoplastic disorders such as multiple myeloma (MM) exhibit high blood levels of apoptotic microparticles. The present study investigated whether these high levels of apoptotic microparticles are associated with insufficient dead cell clearance. Blood samples were collected from patients with MM immediately prior to and 3, 7 and 10 days after the initial cycle of bortezomib-based therapy...
July 2018: Oncology Letters
Jiangtao Shen, Xinru Du, Lingxiu Zhao, Hui Luo, Ziyu Xu
The present retrospective study was designed to compare the pain relief, surgery duration, life quality, survival time and relative prognostic factors in multiple myeloma (MM) bone disease patients with different surgical sites. A total of 65 cases were enrolled and divided into two groups. Group A included patients with lesions located in the spine, while Group B included patients with lesions located in the long bone or soft tissue. Pain relief was measured by the visual analogue scale (VAS), neurological impairment was determined according to Frankel classification, and survival was assessed by the Kaplan-Meier method...
June 2018: Oncology Letters
Shiori Kinoshita, Masaki Ri, Takashi Kanamori, Sho Aoki, Takashi Yoshida, Tomoko Narita, Haruhito Totani, Asahi Ito, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida
Afuresertib (AFU), a novel inhibitor of the serine/threonine kinase AKT, has clinical efficacy as a monotherapy against hematological malignancies and is expected to be used in combination with standard therapies for multiple myeloma (MM). To develop a more effective and less toxic combination of immunomodulatory drugs (IMiDs) for therapy, the antitumor effect of sub-optimal doses of AFU, pomalidomide plus dexamethasone (PD), and the AFU-PD combination on MM cells were examined in the present study. Two MM cell lines, XG-7 and U266, with low sensitivity to both PD and AFU monotherapies, were subjected to these combinations and analyzed...
June 2018: Oncology Letters
Holly Koblish, Yun-Long Li, Niu Shin, Leslie Hall, Qian Wang, Kathy Wang, Maryanne Covington, Cindy Marando, Kevin Bowman, Jason Boer, Krista Burke, Richard Wynn, Alex Margulis, Gary W Reuther, Que T Lambert, Valerie Dostalik Roman, Ke Zhang, Hao Feng, Chu-Biao Xue, Sharon Diamond, Greg Hollis, Swamy Yeleswaram, Wenqing Yao, Reid Huber, Kris Vaddi, Peggy Scherle
The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine protein kinases are overexpressed in many hematologic and solid tumor malignancies and play central roles in intracellular signaling networks important in tumorigenesis, including the Janus kinase-signal transducer and activator of transcription (JAK/STAT) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. The three PIM kinase isozymes (PIM1, PIM2, and PIM3) share similar downstream substrates with other key oncogenic kinases and have differing but mutually compensatory functions across tumors...
2018: PloS One
Chuan Wu, Ting Yang, Yingmin Liu, Yicheng Lu, Yanping Yang, Xiaobo Liu, Xuelian Liu, Long Ye, Yue Sun, Xue Wang, Qingchao Li, Peiyu Yang, Xiaoyuan Yu, Sujun Gao, Shaji Kumar, Fengyan Jin, Yun Dai, Wei Li
1q21 gain is a common cytogenetic abnormality featuring high-risk multiple myeloma (HRMM). However, the molecular mechanism underlying the adverse prognostic effect of 1q21 gain remains largely unclear. Here, we report that ARNT/HIF-1β, a 1q21 gene, is highly expressed in HRMM and induced by microenvironmental hypoxia, which confers drug resistance and correlates with inferior outcome. Analysis of the gene expression profile database revealed that ARNT expression was upregulated in MM and increased with disease progression or in HRMM subtypes (particularly 1q21 gain), while correlated to shorter overall survival...
June 21, 2018: Cancer Medicine
Jin Wang, Lu Qi, Zejuan Wang, Gang Chen, Chen Liu, Ying Liu, Xiaona Liu, Yu Wang, Chunpu Lei, Xinghe Wang
OBJECTIVE: Lenalidomide is a 4-amino-glutaryl derivative of thalidomide and belongs to a new generation of immunomodulatory agents for the treatment of patients with myelodysplastic syndrome and multiple myeloma. The aim of this study is to evaluate the bioequivalence and safety of a capsule containing 25 mg of a test formulation of lenalidomide and a 25 mg Revlimid® capsule in healthy, Chinese adult males for good quality anti-cancer medicine with lower costs. METHODS: This was a single-center, randomized, open-label, single-dose, two-period, crossover pharmacokinetic study...
July 2018: Cancer Chemotherapy and Pharmacology
Shokichi Tsukamoto, Marianne B Løvendorf, Jihye Park, Karma Z Salem, Michaela R Reagan, Salomon Manier, Oksana Zavidij, Mahshid Rahmat, Daisy Huynh, Satoshi Takagi, Yawara Kawano, Katsutoshi Kokubun, Charlotte Albæk Thrue, Kenichi Nagano, Andreas Petri, Aldo M Roccaro, Marzia Capelletti, Roland Baron, Sakari Kauppinen, Irene M Ghobrial
Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically delivered locked nucleic acid (LNA)-modified anti-miR-138 oligonucleotides in suppressing myeloma bone disease...
June 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jennifer L J Heaney, John P Campbell, Gulnaz Iqbal, David Cairns, Alex Richter, J Anthony Child, Walter Gregory, Graham Jackson, Martin Kaiser, Roger Owen, Faith Davies, Gareth Morgan, Janet Dunn, Mark T Drayson
We measured immunosuppression at myeloma diagnosis and assessed the impact on survival in 5826 UK myeloma trial patients. Polyclonal immunoglobulin levels were below normal in 85% of patients and above normal in only 0.4% of cases for IgA, 0.2% for IgM and no cases for IgG. Immunoparesis had a greater impact in recent trials: median overall survival (OS) was up to 3 years longer for patients without immunoparesis compared to the old trials, less than 1 year longer. Median progression-free survival (PFS) was 39%, 36% and 57% longer for patients with normal IgG, IgA and IgM levels, respectively...
June 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Darren L Lath, Clive H Buckle, Holly R Evans, Matthew Fisher, Jenny M Down, Michelle A Lawson, Andrew D Chantry
The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit...
2018: PloS One
Anoosh Shafiee, Soheila Nasiri
A 75-year-old male presented with generalized erythematous, scaly plaques and painless lymphadenopathy. Rosai-Dorfman disease was suspected based on clinical manifestations and confirmed by histopathologic and immune reactivity studies performed on the biopsy obtained from the left supraclavicular lymph node. The patient was also diagnosed with multiple myeloma according to urine electrophoresis, serum light chain assay, and bone marrow biopsy, which were initially performed for evaluation of anemia. This report highlights the dermatological manifestations of Rosai-Dorfman disease with generalized painless lymphadenopathy...
June 2018: Anais Brasileiros de Dermatologia
Ceren Hangül, Orhan Kemal Yücel, Bahar Akkaya, Levent Ündar, Sibel Berker Karaüzüm
No abstract text is available yet for this article.
June 20, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Şerife Solmaz Medeni, Doğuş Türkyılmaz, Celal Acar, Ömür Gökmen Sevindik, Faize Yüksel, Özden Pişkin, Mehmet Ali Özcan, Fatih Demirkan, Bülent Ündar, İnci Alacacıoğlu, Hayri Güner Özsan
INTRODUCTION: High dose melphalan chemotherapy and autologous stem cell transplantation in multiple myeloma ( MM ) is still important treatment modality in transplant eligible patients. At least 2 x 106 /kg CD 34+ cell dose is preferred for sufficient engraftment. Some patients need multiple leukapheresis procedures to reach a required number of the CD34+ cell but this can cause high volume of stem cell product that can not be given in a single day. AIM: Whether the number of infusion days affect engraftment or not, isn't studied before...
June 20, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Valner A F S N Mussel, Max P Ferreira, Maria B F Marques, Maria I Yoshida, Mariana R Almeida, Bernardo L Rodrigues, Wagner N Mussel
Thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy (fourfold the usual sterilizing dose for pharmaceutics). The β polymorph of thalidomide was obtained in an isothermal experiment at 270 °C...
June 2018: Journal of Pharmaceutical Analysis
Matevz Skerget, Barbara Skopec, Vesna Zadnik, Darja Zontar, Helena Podgornik, Katarina Rebersek, Tadej Furlan, Peter Cernelc
OBJECTIVES: In this retrospective study, we evaluated the impact of CD56, CD117, and CD28 expression on clinical characteristics and survival in newly diagnosed myeloma patients treated with bortezomib-based induction therapy. METHODS: We analyzed 110 myeloma patients. Immunophenotype was determined using panels consisting of CD19/CD38/CD45/CD56/CD138 and CD20, CD28, and CD117 were used additionally. All samples were tested for recurrent chromosomal aberrations...
June 19, 2018: Acta Haematologica
K Luczkowska, Z Litwinska, E Paczkowska, B Machalinski
Multiple myeloma (MM) is a disease of unknown, complex etiology that affects primarily older adults. The course of the disease and the patients' survival time are very heterogeneous, but over the last decade, clear progress in the treatment of this incurable disease has been observed. Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib. However, the administration of some of the treatments, e...
April 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
M C Vlot, M den Heijer, R T de Jongh, M G Vervloet, W F Lems, R de Jonge, B Obermayer-Pietsch, A C Heijboer
Measurements of bone markers (BMs) in peripheral blood or urine are a pivotal part of bone research within modern clinical medicine. In recent years the use of BMs increased substantially as they can be useful either to diagnose bone (related) disease and to follow its natural history, but also to monitor the effects of interventions. However, the use of BMs is still complicated mainly due to (pre)analytical variability of these substances, limited accessibility of assays, variable cut-off values in different countries and laboratories and heterogeneous results with regard to clinical implications of measuring BMs in several studies...
June 16, 2018: Bone
Justin Taylor, Dean Pavlick, Akihide Yoshimi, Christina Marcelus, Stephen S Chung, Jaclyn F Hechtman, Ryma Benayed, Emiliano Cocco, Benjamin H Durham, Lillian Bitner, Daichi Inoue, Young Rock Chung, Kerry Mullaney, Justin M Watts, Eli L Diamond, Lee A Albacker, Tariq I Mughal, Kevin Ebata, Brian B Tuch, Nora Ku, Maurizio Scaltriti, Mikhail Roshal, Maria Arcila, Siraj Ali, David M Hyman, Jae H Park, Omar Abdel-Wahab
Rearrangements involving the neurotrophic receptor kinase genes (NTRK1, NTRK2, and NTRK3; hereafter referred to as TRK) produce oncogenic fusions in a wide variety of cancers in adults and children. Although TRK fusions occur in <1% of all solid tumors, inhibition of TRK results in profound therapeutic responses resulting in breakthrough FDA-approval of the TRK inhibitor larotrectinib for adult and pediatric solid tumor patients regardless of histology. In contrast to solid tumors, the frequency of TRK fusions and clinical effects of targeting TRK in hematologic malignancies is unknown...
June 19, 2018: Journal of Clinical Investigation
Y-S Liu, X-B Liu, Y-Y Qiu, T Lan, Y Chen
OBJECTIVE: Pathogenic mechanism of multiple myeloma is still unclear yet. Abnormality in cell autophagy is closely correlated with various orthopedic diseases especially multiple myeloma. Therefore, this study investigated the mechanism of cell autophagy abnormality in multiple myeloma occurrence and clinical implications. MATERIALS AND METHODS: Using multiple myeloma cell line H929 as the model, cells were treated with UV irradiation. Western blot was used to measure the autophagy of H929 cell, expression level of autophagy molecules and activation of autophagy signal pathway such as Wnt...
June 2018: European Review for Medical and Pharmacological Sciences
Rujiao Dong, Guibo Ma, Shunji Zhang, Yujuan Gao, Shuchuan Liu, Yanhua Su
: The introduction of new agents in multiple myeloma therapy has increased the overall response rate and improved clinical outcomes, but the increased risk of thrombotic complications impairs the quality of life of patient and the optimal thromboprophylaxis remains unknown. Increasing evidence has shown that statins can prevent venous thrombosis. Hence, we investigated the effects of simvastatin on multiple myeloma serum-related haemostatic imbalance in endothelial cells in vitro. The effects of simvastatin on procoagulant and anticoagulant protein expression were assessed on mixed multiple myeloma serum-treated human umbilical vein endothelial cells (HUVECs)...
June 18, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Poojan Agarwal, Abhay S Nigam, Vijay Kumar, Sadhna Marwah, Preeti Singh
Light chain myeloma (LCM) is an unusual neoplasm accounting for about 1 8% of all plasma cell myelomas. It is characterized by the absence of a detectable M protein in the serum and urine protein electrophoresis, altered free light chain ratio, bone marrow plasmacytosis and related organ or tissue damage. We report a 60-year-old man with LCM presenting with pancytopenia. Urine Bence Jones proteins were negative and serum protein electrophoresis did not reveal an M-band. However, bone marrow biopsy showed plasmablastic morphology...
September 2017: National Medical Journal of India
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