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Zhe Sha, Jinghui Zhao, Alfred L Goldberg
In certain physiological or pathological states (e.g., starvation, heat shock, or muscle atrophy) and upon drug treatments, the overall rate of protein degradation in cells may increase or decrease. These adaptations and pathological responses can occur through alterations in substrate flux through the ubiquitin-proteasome pathway (UPP), the autophagy-lysosomal system, or both. Therefore, it is important to precisely measure the activities of these degradation pathways in degrading cell proteins under different physiological states or upon treatment with drugs...
2018: Methods in Molecular Biology
Ashtami Banavali, Elvira Neculiseanu, Padma L Draksharam, Sireesha Datla, Maushmi Savjani, Jennifer Park, Gurinder Sidhu, Evelyn O Taiwo
BACKGROUND: Multiple myeloma (MM) is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here. METHODS: This retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood...
September 2018: Journal of Global Oncology
Shebli Atrash, Qing Zhang, Xenofon Papanikolaou, Caleb Stein, Al-Ola Abdallah, Bart Barlogie
PURPOSE: Multiple myeloma (MM) is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated postgerminal B cells. It is a heterogeneous disease both at the genetic level and in terms of clinical outcome. Immunoglobulin M (IgM) MM is a rare subtype of myeloma. Similar to Waldenström macroglobulinemia (WM), patients with MM experience IgM monoclonal gammopathy; however, both diseases are distinct in terms of treatment and clinical behavior. MATERIALS AND METHODS: To shed light on the presentation of IgM MM, its prognosis, and its gene expression profiling, we identified and characterized 21 patients with IgM MM from our database...
September 2018: Journal of Global Oncology
Kaladada I Korubo, Anazoeze J Madu, Helen C Okoye, Benedict Nwogoh
PURPOSE: Novel therapy has dramatically changed the outcome of patients with myeloma. Current National Comprehensive Cancer Network guidelines give bortezomib-based combinations a central role in the management of multiple myeloma (MM). The aim of this survey is to assess the use of bortezomib for the treatment of MM by hematologists practicing in Nigeria. MATERIALS AND METHODS: This is a cross-sectional observational survey. A structured, prevalidated questionnaire was self-administered to different cadres of hematologists...
September 2018: Journal of Global Oncology
Zhaoxin Gu, Xiuxiu Wang, Ru Cheng, Liang Cheng, Zhiyuan Zhong
Bortezomib (BTZ) provides one of the best treatments for multiple myeloma (MM). The efficacy of BTZ is, nevertheless, restricted by its fast clearance, low selectivity, and dose limiting toxicities. Here, we report on targeted BTZ therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib-pinanediol (BP). HA-CCMs loaded with 7.3 BTZ equiv. wt.% exhibited a small size of 78 nm, good stability in 10% FBS, and glutathione-triggered drug release...
September 18, 2018: Acta Biomaterialia
Neil Came
No abstract text is available yet for this article.
September 2018: Cytometry. Part B, Clinical Cytometry
Beth Faiman, Sandra Kurtin, Jocelyn Timko, Linda Gracie-King
BACKGROUND: Understanding aspects of multiple myeloma (MM) from drug delivery to side effect management and survivorship are critical to patient management. The Advanced Clinical Educator (ACE) program in MM combined live and web-based activities to educate nurses to gain mastery of content and achieve ACE status. OBJECTIVES: The primary objectives were to improve ACE candidates' practice skills and knowledge of MM and prepare them to educate others. METHODS: 20 ACE candidates were paired with an advisor and educated through a structured learning program...
October 1, 2018: Clinical Journal of Oncology Nursing
Xingchen Pang, Hongjiao Li, Feng Guan, Xiang Li
The three types of blood cells (red blood cells for carrying oxygen, white blood cells for immune protection, and platelets for wound clotting) arise from hematopoietic stem/progenitor cells in the adult bone marrow, and function in physiological regulation and communication with local microenvironments to maintain systemic homeostasis. Hematological malignancies are relatively uncommon malignant disorders derived from the two major blood cell lineages: myeloid (leukemia) and lymphoid (lymphoma). Malignant clones lose their regulatory mechanisms, resulting in production of a large number of dysfunctional cells and destruction of normal hematopoiesis...
2018: Frontiers in Oncology
Christine Greil, Monika Engelhardt, Gabriele Ihorst, Katja Schoeller, Hartmut Bertz, Reinhard Marks, Robert Zeiser, Justus Duyster, Hermann Einsele, Jürgen Finke, Ralph Wäsch
Despite significantly improved survival and response rates in patients diagnosed with multiple myeloma, it still remains an incurable disease with a poor outcome especially in high-risk groups. Allogeneic stem cell transplantation offers a potentially curative option but is discussed controversially due to considerable treatment related toxicity. We analyzed 109 consecutive myeloma patients who received reduced-intensity conditioning allogeneic transplantation at the Freiburg University Medical Center between 2000 and 2017...
September 20, 2018: Haematologica
Andrew Spencer, Suzanne Lentzsch, Katja Weisel, Hervé Avet-Loiseau, Tomer M Mark, Ivan Spicka, Tamas Masszi, Birgitta Lauri, Mark-David Levin, Alberto Bosi, Vania Hungria, Michele Cavo, Je-Jung Lee, Ajay K Nooka, Hang Quach, Cindy Lee, Wolney Barreto, Paolo Corradini, Chang-Ki Min, Emma C Scott, Asher A Chanan-Khan, Noemi Horvath, Marcelo Capra, Meral Beksac, Roberto Ovilla, Jae-Cheol Jo, Ho-Jin Shin, Pieter Sonneveld, David Soong, Tineke Casneuf, Christopher Chiu, Himal Amin, Ming Qi, Piruntha Thiyagarajah, A Kate Sasser, Jordan M Schecter, Maria-Victoria Mateos
Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow-up is presented. After 19.4 (range: 0 to 27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16...
September 20, 2018: Haematologica
Meletios A Dimopoulos, Jesus San-Miguel, Andrew Belch, Darrell White, Lotfi Benboubker, Gordon Cook, Merav Leiba, James Morton, P Joy Ho, Kihyun Kim, Naoki Takezako, Philippe Moreau, Jonathan L Kaufman, Heather J Sutherland, Marc Lalancette, Hila Magen, Shinsuke Iida, Jin Seok Kim, H Miles Prince, Tara Cochrane, Albert Oriol, Nizar J Bahlis, Ajai Chari, Lisa O' Rourke, Kaida Wu, Jordan M Schecter, Tineke Casneuf, Christopher Chiu, David Soong, A Kate Sasser, Nushmia Z Khokhar, Hervé Avet-Loiseau, Saad Z Usmani
In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow-up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow-up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard ratio, 0...
September 20, 2018: Haematologica
Paola Neri
No abstract text is available yet for this article.
September 20, 2018: Blood
Christoph Driessen, Rouven Müller, Urban Novak, Nathan Cantoni, Daniel Betticher, Nicolas Mach, Axel Rüfer, Ulrich Mey, Panagiotis Samaras, Karin Ribi, Lenka Besse, Andrej Besse, Catherine Berset, Stephanie Rondeau, Hanne Hawle, Felicitas Hitz, Thomas Pabst, Thilo Zander
No abstract text is available yet for this article.
September 20, 2018: Blood
Yoo-Kyung Cho, Sang-Il Kim, Kee-Yong Ha, Young-Hoon Kim, Hyung-Youl Park, Chang-Ki Min
STUDY DESIGN: In vitro experimental study. OBJECTIVES: To investigate the impact of increased osteoblastic activity on the proliferation and survival of MM plasma cells in vitro SUMMARY OF BACKGROUND DATA.: Multiple myeloma (MM) is one of representative hematologic malignancies that cause skeletal-related events (SREs) and dysregulation of bone remodeling is known as a key pathomechanism of disease progression and skeletal-related events. However, decreased proliferation of MM at fracture sites is frequently noted in clinical situations regardless of systemic disease activity METHODS...
September 17, 2018: Spine
Alessandra Bandera, Elisa Colella, Mario Clerici, Giuliano Rizzardini, Andrea Gori
: The widespread use of antiretroviral treatment (ART) results in a significant improvement in immunological condition of people living with HIV (PLWH), that nevertheless experience a significantly increased risk to develop non-Hodgkin lymphoma compared with general population. Despite many literature observations regarding Multiple Myeloma (MM) in PLWH, a consensus on its relevance in HIV infection does not exist.A number of large population studies on Multiple Myeloma in PLWH gave contrasting results, fluctuating from increased standardized incidence ratios (SIRs) to the lack of observed cases of MM...
September 17, 2018: AIDS
Gang Lu, Stephanie Weng, Mary Matyskiela, Xinde Zheng, Wei Fang, Scott Wood, Christine Surka, Reina Mizukoshi, Chin-Chun Lu, Derek Mendy, In Sock Jang, Kai Wang, Mathieu Marella, Suzana Couto, Brian Cathers, James Carmichael, Philip Chamberlain, Mark Rolfe
The cereblon modulating agents (CMs) including lenalidomide, pomalidomide and CC-220 repurpose the Cul4-RBX1-DDB1-CRBN (CRL4CRBN ) E3 ubiquitin ligase complex to induce the degradation of specific neomorphic substrates via polyubiquitination in conjunction with E2 ubiquitin-conjugating enzymes, which have until now remained elusive. Here we show that the ubiquitin-conjugating enzymes UBE2G1 and UBE2D3 cooperatively promote the K48-linked polyubiquitination of CRL4CRBN neomorphic substrates via a sequential ubiquitination mechanism...
September 20, 2018: ELife
Wenzhong Que, Huili Liu, Qinqin Yang, Shanghua Xu
Multiple myeloma (MM) is a plasma cell malignancy. The hepatocyte growth factor (HGF) has been demonstrated to promote MM cell growth. NK4, a splice variant of HGF in which the heavy chain consists of the N-terminal domain and the four kringle domains, is a specific antagonist of HGF that competes with HGF for tyrosine-protein kinase receptor binding. The current study aimed to examine the antiproliferative activity of NK4 on human MM cells and to investigate the underlying mechanism. The results indicated that NK4 suppressed proliferation and induced apoptosis in RPMI 8226 cells...
October 2018: Experimental and Therapeutic Medicine
Carrie K Gomez, Scott R Schiffman, Alok A Bhatt
Calvarial lesions are often asymptomatic and are usually discovered incidentally during computed tomography or magnetic resonance imaging of the brain. Calvarial lesions can be benign or malignant. Although the majority of skull lesions are benign, it is important to be familiar with their imaging characteristics and to recognise those with malignant features where more aggressive management is needed. Clinical information such as the age of the patient, as well as the patient's history is fundamental in making the correct diagnosis...
September 19, 2018: Insights Into Imaging
Yvette N Lamb
Intravenous elotuzumab (Empliciti™), a monoclonal antibody targeting the signalling lymphocytic activation molecule F7 (SLAMF7) glycoprotein, is approved for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in previously-treated adult patients. In the pivotal, multinational, phase III ELOQUENT-2 trial in adults with relapsed and/or refractory multiple myeloma, elotuzumab in combination with lenalidomide and dexamethasone significantly prolonged median progression-free survival (PFS) and increased overall response rate (ORR; co-primary endpoints) compared with lenalidomide and dexamethasone alone...
September 19, 2018: Drugs
S Vincent Rajkumar
Major advances have occurred in the treatment of multiple myeloma, including several new drugs that typically cost more than $100,000 per year. Although the gains in myeloma therapy improve overall survival considerably, they are available to only a fraction of the population of patients with myeloma in the world because of regulatory barriers and cost. Myeloma is an example of what is happening in cancer on a much larger scale. Many of the problems discussed call for a wider discussion across all cancers, but they are amplified in myeloma because of the need for multidrug regimens that combine three or more expensive new drugs for prolonged periods of time...
May 23, 2018: American Society of Clinical Oncology Educational Book
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