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Multiple myeloma

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https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#1
Charvi Nanavati, Donald E Mager
PURPOSE: To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. METHODS: U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures...
January 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28101496/medication-related-osteonecrosis-of-the-jaw-a-preliminary-retrospective-study-of-130-patients-with-multiple-myeloma
#2
Woo-Sung Choi, Jae-Il Lee, Hyun-Joong Yoon, Chang-Ki Min, Sang-Hwa Lee
BACKGROUND: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. METHODS: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ...
December 2017: Maxillofacial Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28101022/necrobiotic-xanthogranuloma-in-a-patient-with-multiple-myeloma
#3
Marlies Wruhs, Robert Feldmann, Isabelle Sawetz, Friedrich Breier, Andreas Steiner
An 82-year-old woman presented with a 9-month history of multiple, well-defined skin lesions on her neck and upper chest, progressively increasing in size. Histological examination of a skin biopsy showed a regular epidermis. In the dermis, granulomatous changes with central necrobiosis were found which extended focally into the subcutaneous fat. The necrobiotic areas were surrounded by Touton cells and foreign-body giant cells. Laboratory analysis revealed leucopenia. Serum electrophoresis and immunofixation disclosed the presence of an IgG-λ paraprotein...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28100400/replication-study-bet-bromodomain-inhibition-as-a-therapeutic-strategy-to-target-c-myc
#4
Fraser Aird, Irawati Kandela, Christine Mantis
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper "BET bromodomain inhibition as a therapeutic strategy to target c-Myc" (Delmore et al., 2011). Here we report the results of those experiments. We found that treatment of human multiple myeloma (MM) cells with the small-molecular inhibitor of BET bromodomains, (+)-JQ1, selectively downregulated MYC transcription, which is similar to what was reported in the original study (Figure 3B; Delmore et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28099937/inactivation-of-ck1%C3%AE-in-multiple-myeloma-empowers-drug-cytotoxicity-by-affecting-akt-and-%C3%AE-catenin-survival-signaling-pathways
#5
Sabrina Manni, Marilena Carrino, Martina Manzoni, Ketty Gianesin, Sara Canovas Nunes, Matteo Costacurta, Laura Quotti Tubi, Paolo Macaccaro, Elisa Taiana, Anna Cabrelle, Gregorio Barilà, Annalisa Martines, Renato Zambello, Laura Bonaldi, Livio Trentin, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1α inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099912/bone-marrow-micro-environment-is-a-crucial-player-for-myelomagenesis-and-disease-progression
#6
Patrizia Mondello, Salvatore Cuzzocrea, Michele Navarra, Michael Mian
Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this disease. In this review we discuss the principal molecules involved in the micro-environment network in multiple myeloma and the currently available therapies targeting them...
January 12, 2017: Oncotarget
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
#7
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/28096095/functional-role-and-therapeutic-targeting-of-p21-associated-kinase-4-pak4-in-multiple-myeloma
#8
Mariateresa Fulciniti, Joaquin Martinez-Lopez, William Senapedis, Stefania Oliva, Rajya Lakshmi Bandi, Nicola Amodio, Yan Xu, Raphael L Szalat, Annamaria Gulla, Mehmet K Samur, Aldo Roccaro, Maria Linares, Michele Cea, Erkan Baloglu, Christian Argueta, Yosef Landesman, Sharon Shacham, Siyuan Liu, Monica Schenone, Shiaw-Lin Wu, Barry Karger, Rao Prabhala, Kenneth C Anderson, Nikhil C Munshi
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095155/understanding-the-relationship-between-care-volume-and-clinical-outcomes-in-multiple-myeloma
#9
Ethan A Halm, Larry D Anderson, David E Gerber
No abstract text is available yet for this article.
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28092996/chromosome-1-amplification-has-similar-prognostic-value-to-del-17p13-and-t-4-14-p16-q32-in-multiple-myeloma-patients-analysis-of-real-life-data-from-the-polish-myeloma-study-group
#10
Norbert Grzasko, Roman Hajek, Marek Hus, Sylwia Chocholska, Marta Morawska, Krzysztof Giannopoulos, Krzysztof Czarnocki, Agnieszka Druzd-Sitek, Barbara Pienkowska-Grela, Jolanta Rygier, Lidia Usnarska-Zubkiewicz, Dominik Dytfeld, Tadeusz Kubicki, Artur Jurczyszyn, Maciej Korpysz, Anna Dmoszynska
The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48...
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#11
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28092909/immune-mediated-neuropathies-following-autologous-stem-cell-transplantation-for-multiple-myeloma-case-series-and-review-of-the-literature
#12
Ghulam Rehman Mohyuddin, Jacqueline Uy, Honhar Medhavi, Muhammad Salman Faisal, Muzaffar H Qazilbash
Neuropathy is a common finding in patients with multiple myeloma. Several different factors can cause neuropathy in these patients, such as the underlying disease itself, medications used for treatment, or immune-mediated processes. Immune-mediated neuropathies (IMN) consist of a heterogeneous spectrum of peripheral nerve disorders. Although IMN is associated with several hematological disorders, it remains a very rare complication of hematopoietic stem cell transplantation (HCT). We describe our experiences of 3 patients with multiple myeloma who experienced IMN following autologous HCT (auto-HCT)...
January 17, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28092869/chronic-myelogenous-leukemia-evolving-after-treatment-of-multiple-myeloma
#13
Denise Wolleschak, Florian H Heidel
No abstract text is available yet for this article.
July 7, 2016: Blood
https://www.readbyqxmd.com/read/28092474/novel-histone-deacetylase-6-hdac6-selective-inhibitors-a-patent-evaluation-wo2014181137
#14
Claudia A Simões-Pires, Philippe Bertrand, Muriel Cuendet
The invention described in this patent (WO2014181137) is related to hydroxamic acid derivatives with inhibitory activity towards histone deacetylases (HDACs), their synthetic process and pharmaceutical formulations, as well as a method for treating patients suffering from a list of selected tumoral, inflammatory, cardiac and chronic disorders. HDACs are known to deacetylate histones and other proteins, which makes HDAC inhibitors able to affect cell survival, cell signaling, transport, and gene expression. Those effects have been associated to the therapeutic success of HDAC inhibitors...
January 16, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28092421/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-heavily-pretreated-multiple-myeloma-a-phase-1-study-in-japan
#15
Kenshi Suzuki, Masaki Ri, Takaaki Chou, Isamu Sugiura, Naoki Takezako, Kazutaka Sunami, Tadao Ishida, Tohru Izumi, Shuji Ozaki, Yoshihisa Shumiya, Kenji Ota, Shinsuke Iida
This is the first study in which the carfilzomib, lenalidomide, and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM). The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m(2) , followed by 27 mg/m(2) ...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28091805/correlation-between-systemic-lupus-erythematosus-and-malignancies-a-cross-sectional-population-based-study
#16
Shir Azrielant, Shmuel Tiosano, Abdulla Watad, Naim Mahroum, Aaron Whitby, Doron Comaneshter, Arnon D Cohen, Howard Amital
Autoimmune conditions reflect dysregulation of the immune system; this may be of clinical significance in the development of several malignancies. Previous studies show an association between systemic lupus erythematosus (SLE) and the development of malignancies; however, their investigations into the development of specific malignancies are inconsistent, and their external validity may be questionable. The main objective of this study is to investigate the association between the presence of SLE and various malignancies, in a large-scale population-based study...
January 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28091419/two-secondary-primary-malignancies-after-bortezomib-therapy-for-multiple-myeloma-a-single-center-experience
#17
Tian-Jiao Guo, Xiao-Jun Huang, Lei Wen, Jin Lu
No abstract text is available yet for this article.
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28091402/geriatric-assessment-to-predict-survival-and-risk-of-serious-adverse-events-in-elderly-newly-diagnosed-multiple-myeloma-patients-a-multicenter-study-in-china
#18
Yu-Ping Zhong, Yi-Zhuo Zhang, Ai-Jun Liao, Su-Xia Li, Chen Tian, Jin Lu
BACKGROUND: Elderly multiple myeloma (MM) patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival (OS) time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM. METHODS: We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28090624/current-strategies-for-the-immunotherapy-of-multiple-myeloma
#19
REVIEW
Tim Luetkens, Sara Yousef, Sabarinath Venniyil Radhakrishnan, Djordje Atanackovic
The introduction of cellular immunotherapies using genetically modified T cells has revolutionized the treatment of patients with B-cell lymphomas. However, despite the progress made in this field, similarly effective immunotherapeutic approaches have not yet been identified for patients with solid tumors or other hematologic malignancies such as multiple myeloma. Here we outline the most promising novel cellular immune strategies for patients with multiple myeloma. In addition, we highlight combinatorial approaches that, it is hoped, will further optimize cellular immunotherapies for myeloma and lead to deep and durable responses and, possibly, even cures...
January 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28090483/emphysematous-osteomyelitis-due-to-escherichia-coli-in-multiple-myeloma
#20
Sung Soo Park, Sung Eun Lee, Chang-Ki Min
No abstract text is available yet for this article.
December 2016: Blood Research
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