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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#2
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#3
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910031/recurrent-cytogenetic-abnormalities-in-multiple-myeloma
#4
Nelson Chun Ngai Chan, Natalie Pui Ha Chan
Multiple myeloma is a heterogeneous disease. Its chromosomal abnormalities have been extensively studied with a view to accurate prognostication and personalized therapy. Here, we describe the techniques commonly employed for elucidating chromosomal aberrations, prognostic impact of recurrent chromosomal abnormalities, and recently updated risk stratification systems.
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
#5
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...
December 2, 2016: 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
#6
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/27908924/excess-weight-as-a-risk-factor-common-to-many-cancer-sites-words-of-caution-when-interpreting-meta-analytic-evidence
#7
Melina Arnold, Andrew G Renehan, Graham A Colditz
For over a decade, excess body weight, commonly categorized as overweight (body mass index, BMI: 25.0 to 29.9 kg/m2) and obesity (BMI: ≥ 30 kg/m2) has been an established incidence risk factor for several adult cancers (1). For 2012, the burden of disease attributed to elevated BMI was estimated as nearly half-million new cancers worldwide, making this the third highest ranked cancer risk factor globally after smoking and infections (ranked second in most western populations) and an important public health problem (2, 3)...
December 1, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27907052/prevalence-and-mortality-related-factors-of-multiple-myeloma-in-taiwan
#8
Jia-Hong Chen, Chi-Hsiang Chung, Yung-Chih Wang, Shun-Neng Hsu, Wen-Yen Huang, Wu-Chien Chien
In this retrospective cohort study based in Taiwan, we reported the current epidemiology of patients with multiple myeloma and analyzed the factors affecting mortality. We identified 7285 patients with newly diagnosed multiple myeloma (MM) between 1997 and 2013 in Taiwan. Privileges data from the National Health Institute Research Database was used, as it is made readily available to the public in electronic format for research purposes. From 1997 to 2013, the average incidence of MM per 100,000 people was 1...
2016: PloS One
https://www.readbyqxmd.com/read/27906664/pearls-oy-sters-plasma-cell-meningitis-an-uncommon-complication-of-multiple-myeloma
#9
Neville Jadeja, Krishna Nalleballe, Jerome Graber
No abstract text is available yet for this article.
November 15, 2016: Neurology
https://www.readbyqxmd.com/read/27906452/primary-prophylaxis-for-venous-thromboembolism-in-ambulatory-cancer-patients-receiving-chemotherapy
#10
REVIEW
Marcello Di Nisio, Ettore Porreca, Matteo Candeloro, Michele De Tursi, Ilaria Russi, Anne Ws Rutjes
BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27905203/efficacy-and-toxicity-of-the-combination-chemotherapy-of-thalidomide-alkylating-agent-and-steroid-for-relapsed-refractory-myeloma-patients-a-report-from-the-korean-multiple-myeloma-working-party-kmmwp-retrospective-study
#11
Jihyun Kwon, Chang-Ki Min, Kihyun Kim, Jae-Joon Han, Joon Ho Moon, Hye Jin Kang, Hyeon-Seok Eom, Min Kyoung Kim, Hyo Jung Kim, Dok Hyun Yoon, Jeong-Ok Lee, Won Sik Lee, Jae Hoon Lee, Je-Jung Lee, Yoon-Seok Choi, Sung Hyun Kim, Sung-Soo Yoon
We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35...
December 1, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27905003/new-agents-in-hsc-mobilization
#12
REVIEW
Mélanie J Domingues, Susan K Nilsson, Benjamin Cao
Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions...
November 30, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#13
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/27904448/mobilization-with-cyclophosphamide-reduces-the-number-of-lymphocyte-subpopulations-in-the-leukapheresis-product-and-delays-their-reconstitution-after-autologous-hematopoietic-stem-cell-transplantation-in-patients-with-multiple-myeloma
#14
Matevz Skerget, Barbara Skopec, Darja Zontar, Peter Cernelc
BACKGROUND: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27904188/cutaneous-manifestations-of-multiple-myeloma
#15
Binodini Behera, Monali Pattnaik, Bharti Sahu, Prasenjeet Mohanty, Swapna Jena, Liza Mohapatra
Multiple myeloma (MM) is a proliferative disorder of plasma cells which produce abnormal immunoglobulin proteins. Skin involvement is rarely found in this disorder. They are either specific or nonspecific lesions. We report four such interesting patients who presented to us initially with common dermatoses such as leukocytoclastic vasculitis, pyoderma gangrenosum, and vesiculobullous disorders and were subsequently diagnosed to have MM. There were no skeletal involvements or renal function abnormality at the time of presentation...
November 2016: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#16
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
https://www.readbyqxmd.com/read/27903750/nuclear-export-of-ubiquitinated-proteins-determines-the-sensitivity-of-colorectal-cancer-to-proteasome-inhibitor
#17
Tingyu Wu, Wei Chen, Yongwang Zhong, Xiaodan Hou, Shengyun Fang, Chen-Ying Liu, Guanghui Wang, Tong Yu, Yu-Yang Huang, Xuesong Ouyang, Henry Q X Li, Long Cui, Yili Yang
Although proteasome inhibitors such as Bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a mono-therapy for solid tumors, including colorectal cancer. We found in the present study that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of Bortezomib on colon cancer cells containing wild type p53, which underwent G2/M cell cycle block and apoptosis...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903712/the-myeloma-stem-cell-concept-revisited-from-phenomenology-to-operational-terms
#18
REVIEW
Hans Erik Johnsen, Martin Bøgsted, Alexander Schmitz, Julie Støve Bødker, Tarec Christoffer El-Galaly, Preben Johansen, Peter Valent, Niklas Zojer, Els Van Valckenborgh, Karin Vanderkerken, Mark van Duin, Pieter Sonneveld, Martin Perez-Andres, Alberto Orfao, Karen Dybkær
The concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19(-)/CD45(low/-)/CD38(high)/CD138(+) malignant plasma cell, but not the CD19(+)/CD38(low/-) memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#19
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27903157/obesity-and-other-cancers
#20
Lin Yang, Bettina F Drake, Graham A Colditz
Purpose Evidence on overweight, obesity, and an increased risk of cancer continues to accumulate and was updated in the 2016 handbook on weight control from the International Agency for Research on Cancer (IARC). The underlying primary data, together with dose-response meta-analysis and, finally, pooled analysis of individual participant data, add insight into the relation between obesity and cancer risk and prognosis. We summarize the evidence for mortality from prostate cancer, hematologic malignancies, and kidney cancer...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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