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multiples myeloma

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https://www.readbyqxmd.com/read/28432594/microrna-transfer-between-bone-marrow-adipose-and-multiple-myeloma-cells
#1
REVIEW
Luna Soley, Carolyne Falank, Michaela R Reagan
PURPOSE OF REVIEW: Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. RECENT FINDINGS: MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28432222/low-expression-of-hexokinase-2-is-associated-with-false-negative-fdg-positron-emission-tomography-in-multiple-myeloma
#2
Leo Rasche, Edgardo Angtuaco, James E McDonald, Amy Buros, Caleb Stein, Charlotte Pawlyn, Sharmilan Thanendrarajan, Carolina Schinke, Rohan Samant, Shmuel Yaccoby, Brian Walker, Joshua Epstein, Maurizio Zangari, Frits van Rhee, Tobias Meissner, Hartmut Goldschmidt, Kari Hemminki, Richard Houlston, Bart Barlogie, Faith E Davies, Gareth J Morgan, Niels Weinhold
18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion weighted magnetic resonance imaging with background signal suppression (DWIBS) are two powerful functional imaging modalities in the evaluation of the malignant plasma cell (PC) disease multiple myeloma (MM). Preliminary observations have suggested that MM patients with extensive disease according to DWIBS may be reported as being disease-free on FDG-PET ("PET-false-negative"). The aim of this study was to describe the proportion of PET-false-negativity in a representative set of 227 newly diagnosed MM patients with simultaneous assessment of FDG-PET and DWIBS, and to identify tumor-intrinsic features associated with this pattern...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#3
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430745/bortezomib-pharmacokinetics-in-tumor-response-and-peripheral-neuropathy-in-multiple-myeloma-patients-receiving-bortezomib-containing-therapy
#4
Sung-Eun Lee, Kyungmee Choi, Seunghoon Han, Jongtae Lee, Taegon Hong, Gab-Jin Park, Dong-Seok Yim, Chang-Ki Min
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient...
April 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28430175/carfilzomib-lenalidomide-dexamethasone-vs-lenalidomide-dexamethasone-in-relapsed-multiple-myeloma-by-previous-treatment
#5
M A Dimopoulos, A K Stewart, T Masszi, I Špička, A Oriol, R Hájek, L Rosiñol, D Siegel, G G Mihaylov, V Goranova-Marinova, P Rajnics, A Suvorov, R Niesvizky, A Jakubowiak, J San-Miguel, H Ludwig, S Ro, S Aggarwal, P Moreau, A Palumbo
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#6
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429426/age-related-health-care-disparities-in-multiple-myeloma
#7
Mathieu Puyade, Gautier Defossez, François Guilhot, Xavier Leleu, Pierre Ingrand
Age is a well-known factor in solid tumours linked to lower adherence to guidelines. Scarce data exist for haematologic malignancies such as multiple myeloma (MM). The aim of the study was to investigate the relationships among age, adherence to guidelines in MM, and overall survival (OS).The Poitou-Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. Diagnosis, staging, prognosis, and first-line treatment were compared to the international guidelines. Three hundred and sixty-seven patients aged 36 to 93 years were included...
April 21, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28428898/severe-acute-hepatitis-b-in-hbv-vaccinated-partner-of-a-patient-with-multiple-myeloma-treated-with-cyclophosphamide-bortezomib-and-dexamethasone-and-autologous-stem-cell-transplant
#8
Majed M Almaghrabi, Kyle J Fortinsky, David Wong
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28428269/low-frequency-mutations-in-ribosomal-proteins-rpl10-and-rpl5-in-multiple-myeloma
#9
Isabel Jf Hofman, Stephanie Patchett, Mark van Duin, Ellen Geerdens, Jelle Verbeeck, Lucienne Michaux, Michel Delforge, Pieter Sonneveld, Arlen W Johnson, Kim De Keersmaecker
No abstract text is available yet for this article.
April 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28428268/salvage-use-of-allogeneic-hsct-after-reduced-intensity-conditioning-from-unrelated-donors-in-multiple-myeloma-a-study-by-the-plasma-cell-disorders-subcommittee-of-the-ebmt-chronic-malignancies-working-party
#10
Mohamad Sobh, Mauricette Michallet, Valerie Dubois, Simona Iacobelli, Linda Koster, Anja Van Biezen, Nathalie Fegueux, Reza Tabrizi, Jürgen Finke, Jean El-Cheikh, Martin Schipperus, Ellen Meijer, Peter von dem Borne, Eefke Petersen, Nigel Russell, Eleni Tholouli, Jakob Passweg, Frédé Ric Garban, Johan Maertens, Patrice Chevalier, Natacha Maillard, Liisa Volin, Sylvie Francois, Bruno Lioure, Yves Beguin, Eliane Gluckman, Annalisa Ruggeri, Laurent Garderet, Nicolaus Kröger
No abstract text is available yet for this article.
April 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28428234/multiple-myeloma-cells-sent-paking
#11
Paola Neri, Nizar J Bahlis
No abstract text is available yet for this article.
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28427695/paraneoplastic-acute-disseminated-encephalomyelitis-associated-with-multiple-myeloma
#12
Lai Yin Law, Kanae Jennifer Nagao
We describe a man recently diagnosed with multiple myeloma who presented with progressive spastic paraparesis, encephalopathy and multifocal MRI lesions with haemorrhage. Brain histopathology was consistent with acute disseminated encephalomyelitis (ADEM) with no new clinicoradiological findings on follow-up. This case emphasises the growing paraneoplastic spectrum, including non-classical but treatable disorders such as ADEM.
April 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28427514/triplet-versus-doublet-combination-regimens-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-a-meta-analysis-of-phase-iii-randomized-controlled-trials
#13
REVIEW
Zhiqiang Sun, Fang Zheng, Suwan Wu, Yanjuan Liu, Hehe Guo, Yichen Liu
During the past decades, several prospective trials had been conducted to assess the efficacy and toxicities of triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma (RRMM), but the results were controversial. We thus performed a systematic literature search to identify relevant trials. Summary hazard ratios (HRs), relative risks (RRs), and 95% confidence intervals (95%CIs) were calculated. A total of 3197 RRMM patients were included for analysis. The pooled results demonstrated that triplet combination therapies significantly improve OS (HR 0...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427509/efficacy-and-safety-of-bortezomib-thalidomide-and-lenalidomide-in-multiple-myeloma-an-overview-of-systematic-reviews-with-meta-analyses
#14
REVIEW
Patricia Melo Aguiar, Tácio de Mendonça Lima, Gisele Wally Braga Colleoni, Sílvia Storpirtis
This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma. We searched the Medline, Scopus, and LILACS databases through August 2016, including systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy and/or safety of bortezomib, thalidomide, or lenalidomide in patients with multiple myeloma. Two authors performed study selection, data extraction, and quality assessment using AMSTAR and GRADE instruments...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#15
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#16
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28425752/use-of-standard-laboratory-methods-to-obviate-routine-dithiothreitol-treatment-of-blood-samples-with-daratumumab-interference
#17
Nicholas J Lintel, Debra K Brown, Diane T Schafer, Farai M Tsimba-Chitsva, Scott A Koepsell, Sara M Shunkwiler
Daratumumab is an antibody currently used in the treatment of patients with refractory multiple myeloma. Blood samples from patients being treated with daratumumab may show panreactivity during pre-transfusion testing. To facilitate the provision of blood components for such patients, it is recommended that a baseline phenotype or genotype be established prior to starting treatment with daratumumab. If patient red blood cells (RBCs) require phenotyping after the start of daratumumab treatment, dithiothreitol (DTT) treatment of the patient's RBCs should be performed...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28425720/a-cereblon-modulator-cc-220-with-improved-degradation-of-ikaros-and-aiolos
#18
Mary E Matyskiela, Weihong Zhang, Hon-Wah Man, George Muller, Godrej Khambatta, Frans Baculi, Matthew Hickman, Laurie LeBrun, Barbra Pagarigan, Gilles Carmel, Chin-Chun Lu, Gang Lu, Mariko Riley, Yoshitaka Satoh, Peter Schafer, Thomas O Daniel, James Carmichael, Brian E Cathers, Philip P Chamberlain
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater...
April 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28425616/statin-use-and-risk-of-multiple-myeloma-an-analysis-from-the-cancer-research-network
#19
Mara M Epstein, George Divine, Chun R Chao, Karen E Wells, Heather Spencer Feigelson, Delia Scholes, Douglas Roblin, Marianne Ulcickas Yood, Lawrence S Engel, Andrew Taylor, Joan Fortuny, Laurel A Habel, Christine C Johnson
Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N=2532)...
April 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28424963/pharmacokinetics-and-safety-of-carfilzomib-in-patients-with-relapsed-multiple-myeloma-and-end-stage-renal-disease-esrd-an-open-label-single-arm-phase-i-study
#20
Hang Quach, Darrell White, Andrew Spencer, P Joy Ho, Divaya Bhutani, Mike White, Sandeep Inamdar, Chris Morris, Ying Ou, Martin Gyger
PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m(2). This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m(2) in normal renal function and ESRD patients. METHODS: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m(2) (cycle 1 day 1-2), escalated to 27 mg/m(2) on cycle 1 day 8; if tolerated, 56 mg/m(2) starting cycle 2 day 1...
April 19, 2017: Cancer Chemotherapy and Pharmacology
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