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Multiple myeloma

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https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#1
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. Patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446993/minimally-invasive-surgical-techniques-for-management-of-painful-metastatic-and-primary-spinal-tumors
#2
REVIEW
Omid Hariri, Ariel Takayanagi, Dan E Miulli, Javed Siddiqi, Frank Vrionis
Patients with metastatic spinal disease are affected by disabling pain. The treatment of spinal metastases is focused on pain reduction and improvement in quality of life. Until recently, many patients with metastatic spinal disease did not qualify as surgical candidates due to the risks of surgery and length of recovery period. However, recent advances in minimally invasive surgery such as kyphoplasty and vertebroplasty allow patients to safely undergo surgery for pain relief with a short recovery period. The studies reviewed here suggest that vertebral augmentation is successful in reducing pain and disability scores in patients with painful metastases and multiple myeloma and are a safe modality to provide lasting pain relief...
March 24, 2017: Curēus
https://www.readbyqxmd.com/read/28446321/-drug-resistant-mechanism-of-multiple-myeloma-and-its-therapy-combined-with-hdaci-review
#3
Liu-Fang Gu, Xiao-Guang Cui, Xing-Mei Cao, She-Ping Chen
Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446300/-clinical-value-of-serum-fructosamine-measurement-in-iga-type-multiple-myeloma
#4
Jing-Yu Zhang, Hong Fan, Li-Xin Chen, Li-Fang Wang, Hong-Fei Wang, Hai-Xiang Shi
OBJECTIVE: To investigate the value of serum fructosamine (FMN) measurement in clinical typing and staging of multiple myeloma(MM) as well as evaluation of curative efficacy and prognosis of IgA type MM. METHODS: The levels of FMN were detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference between the serum FMN levels and different MM types and its relationship with IgA type MM, patients' stages, efficacy and as well as, the effect of FMN level on overall survival (OS) time of IgA type MM patients were analyzed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446299/-effect-of-cik-cells-comined-with-vad-on-short-prognosis-of-patients-with-multiple-myeloma
#5
Wan-Li Chen, Hong-Mei Guan
OBJECTIVE: To explore the effect of CIK cells comined with VAD regimen on prognosis of patients with multiple myeloma(MM). METHODS: Forty-six cases of MM were divided into observation group and control group, the control group was treated by VAD and the observation group was treated by CIK cells comined with VAD. The prognosis between 2 groups was compared. RESULTS: The total efficiency was not significantly different between the 2 groups (P>0...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446298/-clinical-effects-of-different-chemotherapeutic-regimens-on-the-patients-with-multiple-myeloma
#6
Shu Wang, Hong-Mei Guan
OBJECTIVE: To explore the clinical effects of T-VD regimen (bortezomib+dexamethasone+thalidomid) and T-VAD regimen (vincristine+adriamycin+dexamethasone+thalidomide) on the patients with multiple myeloma(MM). METHODS: Thirty cases of MM treated by T-VD(T-VD group) and 30 cases of MM treated by T-VAD(T-VAD group) from April 2010 to April 2012 were included in this study. The clinical effects and long-term survival were compared betwwen these 2 groups. RESULTS: Both the CR and ORR in T-VD group were higher than those in T-VAD group(P<0...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446297/-prophylaxis-of-bortezomib-induced-peripheral-neuropathy-in-patients-with-multiple-myeloma-by-high-dose-intravenous-mecobalamin
#7
Li-Li Zhang, Yi-Hao Wang, Zong-Hong Shao, Jun Ma
OBJECTIVE: To evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM). METHODS: A total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446296/-expression-of-cc-chemokine-receptor-7-in-patiens-with-multiple-myeloma-and-its-relationship-with-extramedullary-disease
#8
Ya-Nan Wang, Si-Lin Gan, Fei-Fei Wu, Wei-Min Wang, Shuai-Quan Li, Jie Ma, Rong Guo, Zhong-Xing Jiang, Bao-Hong Yue, Hui Sun
OBJECTIVE: To investigate the expression of CC-chemokine receptor 7(CCR7) in patients with multiple myeloma(MM) and its correlation with clinical features of MM. METHODS: The level of CCR7 expression in bone marrow samples from 53 newly diagnosed MM patients was detected by flow cytometry(FCM). Statistical methods were used to analyze the correlation between CCR7 expression and clinical features, such as sex, age, M protein, peripheral blood cell count, biochemical indicators, plasma cell ratio of bone marrow, immunophenotype, osteopathy and extramedullary disease...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446295/-circulating-serum-microrna-as-diagnostic-biomarkers-for-multiple-myeloma
#9
Yan-Ni Xu, Cui-Rong Xiao, Ying-Dan Huang, Quan-Yi Lu
OBJECTIVE: To investigate the diagnostic value of circulating serum miRNA for multiple myeloma. METHODS: Forty blood samples from patients with multiple myeloma were collected from July 2013 to June 2014 in Department of Hematology, Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR-155, miR-16 and miR-92a) circulating in the different stages of patients with multiple myeloma and evaluate the diagnostic value for patients with multiple myeloma...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446294/-effect-of-hedgehog-signaling-pathway-abnormality-on-chemothe-rapeutic-resistance-of-multiple-myeloma
#10
Jia-Sheng Hu, Xiao Huang, Ying-Dan Huang, Yan-Yan Lu, Quan-Yi Lu
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445037/discovery-of-5-azaindazole-gne-955-as-a-potent-pan-pim-inhibitor-with-optimized-bioavailability
#11
Xiaojing Wang, Aleksandr Kolesnikov, Suzanne Tay, Grace Chan, Qi Chao, Steven Do, Jason Drummond, Allen J Ebens, Ning Liu, Justin Q Ly, Eric Harstad, Huiyong Hu, John G Moffat, Veerendra Munugalavadla, Jeremy M Murray, Dionysos Slaga, Vickie Tsui, Matthew Volgraf, Heidi J A Wallweber, Jae H Chang
Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. Here, we describe our continued efforts in optimizing a lead series by improving bioavailability while maintaining high inhibitory potency against all three Pim kinase isoforms. The discovery of extensive intestinal metabolism and major metabolites helped refine our design strategy and we observed that optimizing the pharmacokinetic properties first and potency second was a more successful approach than the reverse...
April 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28442888/new-developments-in-the-treatment-of-multiple-myeloma-clinical-utility-of-daratumumab
#12
REVIEW
Cian McEllistrim, Janusz Krawczyk, Michael E O'Dwyer
Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28442502/ribonucleotide-reductase-large-subunit-rrm1-as-a-novel-therapeutic-target-in-multiple-myeloma
#13
Morihiko Sagawa, Hiroto Ohguchi, Takeshi Harada, Mehmet K Samur, Yu-Tzu Tai, Nikhil C Munshi, Masahiro Kizaki, Teru Hideshima, Kenneth C Anderson
Purpose: To investigate the biologic and clinical significance of ribonucleotide reductase (RR) in multiple myeloma (MM). <p>Experimental Design: We assessed the impact of RR expression on patient outcome in MM. We then characterized the effect of genetic and pharmacological inhibition of RRM1 on MM growth and survival using siRNA and clofarabine (CLO), respectively, both in vitro and in vivo mouse xenograft model.</p> <p>Results: Newly diagnosed MM patients with higher RRM1 expression have shortened survival...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#14
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28441149/epigenetic-regulatory-mutations-and-epigenetic-therapy-for-multiple-myeloma
#15
Daphné Dupéré-Richer, Jonathan D Licht
PURPOSE OF REVIEW: Next generation sequencing and large-scale analysis of patient specimens has created a more complete picture of multiple myeloma (MM) revealing that epigenetic deregulation is a prominent factor in MM pathogenesis. RECENT FINDINGS: Over half of MM patients have mutations in genes encoding epigenetic modifier enzymes. The DNA methylation profile of MM is related to the stage of the disease and certain classes of mutations in epigenetic modifiers are more prevalent upon disease relapse, suggesting a role in disease progression...
April 22, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28439985/the-utility-of-mass-fix-to-detect-and-monitor-monoclonal-proteins-in-the-clinic
#16
Paolo Milani, David L Murray, David R Barnidge, Mindy C Kohlhagen, John R Mills, Giampaolo Merlini, Surendra Dasari, Angela Dispenzieri
The detection and quantification of monoclonal-proteins (M-proteins) are necessary for the diagnosis and evaluation of response in plasma cell dyscrasias. Immunoglobulin enrichment-coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX) is a simple and inexpensive method to identify M-proteins, but its clinical generalizability has not yet been elucidated. We compared MASS-FIX to protein electrophoresis (PEL), serum/urine immunofixation-electrophoresis (IFE) and quantitative serum free-light chain (FLC) for the identification of M-proteins in different clinical diagnoses...
April 25, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28439907/igg4-related-disease-with-bone-marrow-involvement-mimicking-multiple-myeloma
#17
Shih-Hao Tang, Ming-Hui Lin, Jeng-Shiun Du, Yi-Chang Liu, Hui-Hua Hsiao, Ta-Chih Liu
No abstract text is available yet for this article.
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#18
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439700/filgrastim-alone-versus-pegylated-filgrastim-alone-for-autologous-peripheral-blood-stem-cells-mobilization-in-newly-diagnosed-multiple-myeloma-patients
#19
Barbara Skopec, Matevz Skerget, Darja Zontar, Vesna Zadnik, Samo Zver
BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is the recommended standard upfront treatment for transplant eligible myeloma patients. Considering possible complications related to chemotherapy-cytokine mobilization, cytokine-alone mobilization is often used. We compared mobilization with filgrastim alone to pegfilgrastim alone in newly diagnosed myeloma patients after induction treatment with bortezomib and dexamethasone. The comparison was made between peripheral blood stem cell (PBSC) yields, number of apheresis, hematopoietic stem cell subsets, and time to neutrophil and platelet engraftment after aHSCT...
April 24, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28439109/efficacy-and-safety-of-carfilzomib-regimens-in-multiple-myeloma-patients-relapsing-after-autologous-stem-cell-transplant-aspire-and-endeavor-outcomes
#20
P Hari, M-V Mateos, R Abonour, S Knop, W Bensinger, H Ludwig, K Song, R Hajek, P Moreau, D S Siegel, S Feng, M Obreja, S K Aggarwal, K Iskander, H Goldschmidt
Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone)...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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