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https://www.readbyqxmd.com/read/28099396/successful-treatment-of-refractory-langerhans-cell-histiocytosis-of-the-choroid-plexus-in-a-child-with-pulse-dexamethasone-and-lenalidomide
#1
Ramya Uppuluri, Sreejith Ramachandrakurup, Ravikanth Balaji, Divya Subburaj, Atish Bakane, Revathi Raj
Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. Salvage treatments available are both expensive and highly toxic. On the basis of the pathophysiology of LCH, we used a novel protocol including pulse dexamethasone and lenalidomide in a child with refractory LCH involving the choroid plexus, which resulted in durable remission with minimal toxicity. The protocol was extrapolated from the FIRST trial for patients with multiple myeloma. We present the clinical course, treatment protocol, and outcome in this child, who is at present disease free and in remission 18 months posttreatment...
January 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28089441/prognostic-implications-of-monosomies-in-patients-with-multiple-myeloma
#2
Sang-Yong Shin, Hyeon-Seok Eom, Ji Yeon Sohn, Hyewon Lee, Boram Park, Jungnam Joo, Ja-Hyun Jang, Mi-Na Lee, Jung Kwon Kim, Sun-Young Kong
BACKGROUND: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. MATERIALS AND METHODS: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH)...
December 26, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28078910/gain-of-chromosome-1q-portends-worse-prognosis-in-multiple-myeloma-despite-novel-agent-based-induction-regimens-and-autologous-transplantation
#3
Gunjan L Shah, Heather Landau, Dory Londono, Sean M Devlin, Satyajit Kosuri, Alexander M Lesokhin, Nikoletta Lendvai, Hani Hassoun, David J Chung, Guenther Koehne, Suresh C Jhanwar, Ola Landgren, Ross Levine, Sergio A Giralt
We aimed to identify whether the use of autologous hematopoietic cell transplantation (HCT) impacts outcomes for multiple myeloma patients with gains of chromosome 1q (+1q). We retrospectively identified 95 patients, 21% having +1q. For patients with +1q, the overall response rate to induction was 85%, with 40% having ≥ VGPR and 20% achieving a CR, similar to non +1q patients (p = .64). The median PFS from diagnosis with +1q was 2.1 years (95% CI: 1.2-not reached (NR)) vs 4.3 years (95% CI: 3...
January 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28076253/presenting-signs-of-multiple-myeloma-and-the-effect-of-diagnostic-delay-on-the-prognosis
#4
Neta Goldschmidt, Leora Zamir, Alina Poperno, Nathan R Kahan, Ora Paltiel
BACKGROUND: Presenting symptoms of multiple myeloma (MM) are vague and nonspecific. Early detection poses a diagnostic challenge in primary care. We assessed whether clinical and laboratory data could provide early clues to MM diagnosis and whether time to detection affects survival. METHODS: A retrospective population-based study, including 110 men and women diagnosed with MM between 2002 and 2011, and matched cancer-free controls presenting with back pain. Clinical and laboratory data were extracted from medical records for the 2-year period prior to diagnosis of MM/back pain complaint...
November 2016: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/28069266/the-clinicopathologic-characteristics-of-kidney-diseases-related-to-monotypic-iga-deposits
#5
Marguerite Vignon, Camille Cohen, Stanislas Faguer, Laure-Hélène Noel, Celine Guilbeau, Marion Rabant, Sarah Higgins, Aurélie Hummel, Alexandre Hertig, Hélène Francois, Moglie Lequintrec, Eve Vilaine, Bertrand Knebelmann, Jacques Pourrat, Dominique Chauveau, Jean-Michel Goujon, Vincent Javaugue, Guy Touchard, Khalil El Karoui, Frank Bridoux
Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in 19 referred patients...
January 6, 2017: Kidney International
https://www.readbyqxmd.com/read/28061987/management-of-multiple-myeloma-in-resource-constrained-settings
#6
REVIEW
Lalit Kumar, Ranjit Kumar Sahoo
The prognosis of patients with multiple myeloma (MM) has improved significantly in the past two decades. This is attributed to use of novel agents for induction, high-dose chemotherapy and autologous stem cell transplantation (ASCT), maintenance therapy, and improved supportive care. Currently, evidence-based management guidelines/recommendations developed by International societies/groups are being followed partially in low-resource settings. Lack of quality diagnostics (eg, cytogenetics/fluorescence in situ hybridization (FISH), serum free light chains), novel therapeutics, and trained manpower, and limited financial resources are key challanges...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28038447/proteome-alterations-associated-with-transformation-of-multiple-myeloma-to-secondary-plasma-cell-leukemia
#7
Alexey Zatula, Aida Dikic, Celine Mulder, Animesh Sharma, Cathrine B Vågbø, Mirta M L Sousa, Anders Waage, Geir Slupphaug
Plasma cell leukemia is a rare and aggressive plasma cell neoplasm that may either originate de novo (primary PCL) or by leukemic transformation of multiple myeloma (MM) to secondary PCL (sPCL). The prognosis of sPCL is very poor, and currently no standard treatment is available due to lack of prospective clinical studies. In an attempt to elucidate factors contributing to transformation, we have performed super-SILAC quantitative proteome profiling of malignant plasma cells collected from the same patient at both the MM and sPCL stages of the disease...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28024514/-advances-of-crbn-in-immunomodulatory-drugs-for-multiple-myeloma-review
#8
Ran An, Jian Hou
Multiple myeloma is a plasma cell malignant clone proliferation diseases and has been remained incurable. In the resent years, the widespread application of immunomodulatory drugs (IMiD) have made a great progress in the treatment of multiple myeloma, greatly improved the complete remission rate and prolonged the overall survival of MM patients. According to recent researches, CRBN (cereblon) plays an important role in mediating anti-myeloma effects of IMiD, and its expression correlated with the effect of IMiD treatment and the prognosis of multiple myeloma...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28008174/autologous-transplant-vs-oral-chemotherapy-and-lenalidomide-in-newly-diagnosed-young-myeloma-patients-a-pooled-analysis
#9
F Gay, S Oliva, M T Petrucci, V Montefusco, C Conticello, P Musto, L Catalano, A Evangelista, S Spada, P Campbell, R Ria, M Salvini, M Offidani, A M Carella, P Omedé, A M Liberati, R Troia, A M Cafro, A Malfitano, A P Falcone, T Caravita, F Patriarca, A Nagler, A Spencer, R Hajek, A Palumbo, M Boccadoro
In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival-1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival-2 (PFS2), overall survival (OS)...
December 23, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28002971/new-and-developing-therapies-for-al-amyloidosis
#10
Giulia Zumbo, Omid Sadeghi-Alavijeh, Philip N Hawkins, Marianna Fontana
Systemic light-chain (AL) amyloidosis is an infiltrative disorder associated with an underlying plasma cells dyscrasia, in which monoclonal immunoglobulin light chains accumulate in an abnormal misfolded form as amyloid fibrils in the extracellular space. Symptoms and prognosis are governed by which organs are affected, and cardiac involvement is the major determinant of survival. Diagnosis requires demonstration of amyloid deposition and confirmation of the fibril protein type. Areas covered: This review will focus on the available treatments for systemic AL amyloidosis and on new drug targets and therapeutic approaches...
December 29, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28000886/hsa-mir-631-resensitizes-bortezomib-resistant-multiple-myeloma-cell-lines-by-inhibiting-ubch10
#11
Hao Xi, Lu Li, Juan Du, Ran An, Rong Fan, Jing Lu, Yin-Xiang Wu, Shu-Xie Wu, Jian Hou, Li-Ming Zhao
Although bortezomib (BTZ) remains a first-line agent for multiple myeloma (MM) therapy, the development of BTZ resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to BTZ. This study demonstrated, for the first time, that UbcH10 is highly expressed in BTZ-resistant myeloma cell lines U-266/BTZ, NCI-H929/BTZ and RPMI-8226/BTZ, which is attributed to the inactivation of post-transcriptional control. The in-depth study revealed that during the development of BTZ resistance in these cells, the hsa-miR-631 levels were decreased, which resulted in the increased expression of the target gene UbcH10...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27924158/lycorine-downregulates-hmgb1-to-inhibit-autophagy-and-enhances-bortezomib-activity-in-multiple-myeloma
#12
Mridul Roy, Long Liang, Xiaojuan Xiao, Yuanliang Peng, Yuhao Luo, Weihua Zhou, Ji Zhang, Lugui Qiu, Shuaishuai Zhang, Feng Liu, Mao Ye, Wen Zhou, Jing Liu
Multiple myeloma (MM) is largely incurable and drug-resistant. Novel therapeutic approaches such as inhibiting autophagy or rational drug combinations are aimed to overcome this issue. In this study, we found that lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy. We identified High mobility group box 1 (HMGB1), an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment and as a critical mediator of lycorine activity...
2016: Theranostics
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#13
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#14
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#15
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27910020/cytoplasmic-immunoglobulin-light-chain-revelation-and-interphase-fluorescence-in-situ-hybridization-in-myeloma
#16
Sarah Moore, Jeffrey M Suttle, Mario Nicola
The cytogenetic analysis of plasma cell myeloma (PCM) allows stratification of patients so that prognosis may be determined and appropriate therapeutic options can be discussed. Owing to the patchy nature of the disease in the bone marrow (BM), the low proliferative activity of plasma cells and the cryptic nature of some PCM-associated cytogenetic changes, karyotypic analysis in this disease should be augmented with targeted interphase fluorescence in situ hybridization (FISH). Immunofluorescent revelation of cytoplasmic immunoglobulin light chains, together with interphase FISH (cIg-FISH), allows the identification of plasma cells within a sample so that they may be scored preferentially...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#17
I J F Hofman, M van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27909220/role-of-serum-free-light-chain-assay-in-the-detection-of-early-relapse-and-prediction-of-prognosis-after-relapse-in-multiple-myeloma-patients-treated-upfront-with-novel-agents
#18
Paola Tacchetti, Annalisa Pezzi, Elena Zamagni, Lucia Pantani, Serena Rocchi, Beatrice Anna Zannetti, Katia Mancuso, Ilaria Rizzello, Michele Cavo
No abstract text is available yet for this article.
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#19
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#20
Dongxue Wang, Hideharu Hashimoto, Xing Zhang, Benjamin G Barwick, Sagar Lonial, Lawrence H Boise, Paula M Vertino, Xiaodong Cheng
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5'-CACGTG-3'. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms...
November 29, 2016: Nucleic Acids Research
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