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https://www.readbyqxmd.com/read/29244720/functional-imaging-with-18f-fdg-pet-ct-and-diffusion-weighted-imaging-dwi-in-early-response-evaluation-of-combination-therapy-of-elotuzumab-lenalidomide-and-dexamethasone-in-a-relapsed-multiple-myeloma-patient
#1
Christos Sachpekidis, Antonia Dimitrakopoulou-Strauss, Stefan Delorme, Hartmut Goldschmidt
Elotuzumab is the first monoclonal antibody approved for the treatment of relapsed-refractory multiple myeloma (MM) in combination with lenalidomide, an immunodulatory drug, and dexamethasone. We report on a multiply pre-treated MM patient with disease progression due to appearance of new focal lesions on imaging modalities, who was started on a combination treatment of elotuzumab, lenalidomide, and dexamethasone. After completion of three cycles of the new therapy the patient responded very well with a major decline of serological myeloma activity parameters serum monoclonal protein, kappa light chains, free light chains (FLC) ratio...
December 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/29244706/streptococcus-pneumoniae-osteomyelitis-in-a-25-year-old-man-as-the-initial-presentation-of-multiple-myeloma-a-case-report
#2
Tracy Webber, Michael Lawlor, Tessa Balach
CASE: We report the case of a 25-year-old man with femoral Streptococcus pneumoniae pyomyositis as well as hypercalcemia, mild anemia, and elevated inflammatory markers; he subsequently was diagnosed with immunoglobulin G (IgG) kappa multiple myeloma. CONCLUSION: Multiple myeloma most commonly affects patients who are >60 years of age, and causes clinical symptoms from anemia, lytic bone lesions, hypercalcemia, and renal failure. These findings and a monoclonal protein spike serve as initial diagnostic and treatment criteria...
July 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29244631/initial-results-of-peripheral-blood-stem-cell-mobilization-collection-cryopreservation-and-engraftment-after-autologous-transplantation-confirm-that-the-capacity-building-approach-offers-good-chances-of-success-in-critical-contexts-a-kurdish-italian-cooperative
#3
Ignazio Majolino, Dereen Mohammed, Dastan Hassan, Francesco Ipsevich, Chra Abdullah, Rebar Mohammed, Angelo Palmas, Marco Possenti, Diana Noori, Dlir Ali, Harem Karem, Salah Salih, Michele Vacca, Claudia Del Fante, Angelo Ostuni, Andrea Frigato, Maria Speranza Massei, Annunziata Manna, Stefania Vasta, Marcela Gabriel, Marta Verna, Attilio Rovelli, Valentino Conter, Kosar Ali, Dosti Othman
Introduction At Hiwa Cancer Hospital (Sulaymaniyah, Iraqi Kurdistan) after the center was started by a cooperative project in June 2016, autologous transplantation was developed. Patients and Methods To develop the project, the capacity-building approach was adopted, with on-site training and coaching of personnel, educational meetings, lectures, on-the-job training, and the implementation of quality management planning. Results Here, we report initial results of peripheral-blood stem-cell mobilization and collection of the first 27 patients (age 12 to 61 years; 19 males and 8 females; multiple myeloma, n = 10; plasma cell leukemia, n = 1; Hodgkin lymphoma, n = 12; non-Hodgkin lymphoma, n = 3; and acute myeloid leukemia, n = 1)...
December 15, 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/29242516/mronj-risk-of-adjuvant-bisphosphonates-in-early-stage-breast-cancer
#4
V Patel, J Mansi, S Ghosh, J Kwok, M Burke, D Reilly, N Nizarali, C Sproat, K Chia
Medication-related osteonecrosis of the jaw (MRONJ) has most commonly been associated with bisphosphonates. The routine uses of these drugs are now well established predominantly in metastatic cancer with bone involvement, multiple myeloma, hypercalcaemia, osteoporosis and Paget's disease. Recently, however, the use of bisphosphonates in early breast cancer has shown a reduction in breast cancer recurrence and breast cancer deaths. This new indication for their use approximates to a further 20,000 women per year in the UK being prescribed bisphosphonates...
December 15, 2017: British Dental Journal
https://www.readbyqxmd.com/read/29242101/epigenetic-silencing-of-evl-mir-342-in-multiple-myeloma
#5
Zhenhai Li, Kwan Yeung Wong, Godfrey Chi-Fung Chan, Wee-Joo Chng, Chor Sang Chim
miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29241676/breast-cancer-and-synchronous-multiple-myeloma-as-a-diagnostic-challenge-case-report-and-review-of-literature
#6
Marcin Sokołowski, Grzegorz Mazur, Aleksandra Butrym
Multiple myeloma is a hematological malignancy, which sometimes creates difficulties in diagnosis, based on the presence of monoclonal protein in serum/urine and plasmocyte infiltration in the bone marrow, and on the other hand, synchronous cancers are also a diagnostic challenge. We present a case report of a patient with concurrent breast cancer and multiple myeloma. A 68-year-old woman was admitted to the hospital with diagnosis of left breast cancer in first stage of the disease. In the past, she had had several episodes of thrombocytopenia, leucocytosis, and mild anaemia, which were followed by hematologist in outpatient setting...
November 22, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29241222/flavopiridol-enhances-abt-199-sensitivity-in-unfavourable-risk-multiple-myeloma-cells-in-vitro-and-in-vivo
#7
Liang Zhou, Yu Zhang, Deepak Sampath, Joel Leverson, Yun Dai, Maciej Kmieciak, Matthew Nguyen, Robert Z Orlowski, Steven Grant
BACKGROUND: The BCL-2-specific BH3-mimetic ABT-199 (venetoclax) has been reported to be principally active against favourable-risk multiple myeloma (MM) cells, prompting efforts to extend its activity to include more resistant, higher-risk MM subsets. METHODS: Effects of the CDK9 inhibitor flavopiridol (FP; alvocidib) on responses to ABT-199 were examined in MM cells. Cell death and protein expression were evaluated by western blot and immunofluorescence. Xenograft models were used to study combination effects in vivo...
December 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29239143/role-of-plasmapheresis-in-the-management-of-acute-kidney-injury-in-patients-with-multiple-myeloma-should-we-abandon-it
#8
Vedran Premuzic, Josip Batinic, Pavle Roncevic, Nikolina Basic-Jukic, Damir Nemet, Bojan Jelakovic
The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group...
December 14, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29239009/falls-in-older-adults-with-multiple-myeloma
#9
Tanya M Wildes, Mark A Fiala
To examine the prevalence of falls, factors associated with falls and the relationship between falls and survival in older adults with multiple myeloma METHODS: In an analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) linked database, we examined 405 older adults with MM and 513 matched non-cancer controls. The primary outcome was self-reported within the past 12 months. Age, race, gender, symptoms and comorbidities were self-reported in the MHOS. Survival was calculated from SEER data RESULTS: Of the patients with MM, 171 were within 1 year of diagnosis (cohort 1) and 234 were ≥1 year post-diagnosis (cohort 2)...
December 14, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29237959/cardiotoxicity-associated-with-bortezomib-a-single-center-experience
#10
Murali Krishna Gurram, Swaroopa Pulivarthi, Kirsten Ehresmann, Josy Mathew
BACKGROUND: Studies evaluating the prevalence of cardiotoxicity associated with bortezomib are limited. We proposed this study to evaluate the prevalence of cardiotoxicity associated with bortezomib and its relation to multiple myeloma and other malignancies. MATERIALS AND METHODS: This is a retrospective, chart review study. Subjects who received bortezomib at the HealthEast care system for various oncologic conditions were evaluated after obtaining IRB approval...
October 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29235380/pharmacokinetic-drug-evaluation-of-ixazomib-citrate-for-the-treatment-of-multiple-myeloma
#11
Marco Salvini, Rossella Troia, Davide Giudice, Chiara Pautasso, Mario Boccadoro, Alessandra Larocca
multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients...
December 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29233917/c-reactive-protein-promotes-bone-destruction-in-human-myeloma-through-the-cd32-p38-mapk-twist-axis
#12
Jing Yang, Zhiqiang Liu, Huan Liu, Jin He, Jianling Yang, Pei Lin, Qiang Wang, Juan Du, Wencai Ma, Zheng Yin, Eric Davis, Robert Z Orlowski, Jian Hou, Qing Yi
Bone destruction is a hallmark of myeloma and affects 80% of patients. Myeloma cells promote bone destruction by activating osteoclasts. In investigating the underlying mechanism, we found that C-reactive protein (CRP), a protein secreted in increased amounts by hepatocytes in response to myeloma-derived cytokines, activated myeloma cells to promote osteoclastogenesis and bone destruction in vivo. In mice bearing human bone grafts and injected with multiple myeloma cells, CRP bound to surface CD32 (also known as FcγRII) on myeloma cells, which activated a pathway mediated by the kinase p38 MAPK and the transcription factor Twist that enhanced the cells' secretion of osteolytic cytokines...
December 12, 2017: Science Signaling
https://www.readbyqxmd.com/read/29231133/daratumumab-plus-bortezomib-melphalan-and-prednisone-for-untreated-myeloma
#13
María-Victoria Mateos, Meletios A Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna M Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Robin Carson, Wendy Crist, William Deraedt, Huong Nguyen, Ming Qi, Jesus San-Miguel
Background The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. Methods In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression...
December 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29230672/the-role-of-b-cell-maturation-antigen-in-the-biology-and-management-of-and-as-a-potential-therapeutic-target-in-multiple-myeloma
#14
Eric Sanchez, Emily J Smith, Moryel A Yashar, Saurabh Patil, Mingjie Li, Autumn L Porter, Edward J Tanenbaum, Remy E Schlossberg, Camilia M Soof, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James R Berenson
B-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab-drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA-directed ADCs...
December 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29229668/multiple-myeloma-and-bone-the-fatal-interaction
#15
Silvia Marino, G David Roodman
Multiple myeloma (MM) is the second-most-common hematologic malignancy and the most frequent cancer to involve bone. MM bone disease (MMBD) has devastating consequences for patients, including dramatic bone loss, severe bone pain, and pathological fractures that markedly decrease the quality of life and impact survival of MM patients. MMBD results from excessive osteoclastic bone resorption and persistent suppressed osteoblastic bone formation, causing lytic lesions that do not heal, even when patients are in complete and prolonged remission...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29228867/long-non-coding-rna-ccat1-promotes-multiple-myeloma-progression-by-acting-as-a-molecular-sponge-of-mir-181a-5p-to-modulate-hoxa1-expression
#16
Li Chen, Ning Hu, Chao Wang, Hongmian Zhao, Yueli Gu
Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, little is known about its functional role and molecular mechanism in MM. The aim of this study was to investigate the clinical and biological significance of CCAT1 in MM. Our data showed that the relative expression levels of CCAT1 were significantly upregulated in MM tissues and cell lines compared with healthy donors and normal plasma cells (nPCs)...
December 11, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29228738/cd24-cd27-cd36-and-cd302-gene-expression-for-outcome-prediction-in-patients-with-multiple-myeloma
#17
Elina Alaterre, Sebastien Raimbault, Hartmut Goldschmidt, Salahedine Bouhya, Guilhem Requirand, Nicolas Robert, Stéphanie Boireau, Anja Seckinger, Dirk Hose, Bernard Klein, Jérôme Moreaux
Multiple myeloma (MM) is a B cell neoplasia characterized by clonal plasma cell (PC) proliferation. Minimal residual disease monitoring by multi-parameter flow cytometry is a powerful tool for predicting treatment efficacy and MM outcome. In this study, we compared CD antigens expression between normal and malignant plasma cells to identify new potential markers to discriminate normal from malignant plasma cells, new potential therapeutic targets for monoclonal-based treatments and new prognostic factors. Nine genes were significantly overexpressed and 16 were significantly downregulated in MMC compared with BMPC (ratio ≥2; FDR CD24, CD27, CD36 and CD302) was associated with a prognostic value in two independent cohorts of patients with MM (HM cohort and TT2 cohort, n=345)...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228683/lenalidomide-overcomes-the-immunosuppression-of-regulatory-cd8-cd28-t-cells
#18
Brigitte Neuber, Jingying Dai, Wjahat A Waraich, Mohamed H S Awwad, Melanie Engelhardt, Michael Schmitt, Sergej Medenhoff, Mathias Witzens-Harig, Anthony D Ho, Hartmut Goldschmidt, Michael Hundemer
Although lenalidomide and pomalidomide are well-established treatment options in patients with multiple myeloma, their immune-modulating effects are not fully understood. While CD8+CD28- regulatory T-cells in patients with hematologic disorders display a known immune-escape mechanism, we show that lenalidomide can overcome the immunosuppressive impact of CD8+CD28- T-cells. We analyzed in vitro the antigen-specific T-cell responses of healthy donors and patients with multiple myeloma with or without the addition of autologous CD8+CD28- T-cells in the absence and presence of lenalidomide...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#19
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29227648/quinazolinone-based-anticancer-agents-synthesis-anti-proliferative-sar-anti-tubulin-activity-and-tubulin-co-crystal-structure
#20
Wolfgang Dohle, Fabrice L Jourdan, Gregory Menchon, Andrea E Prota, Paul A Foster, Pascoe Mannion, Ernest Hamel, Mark P Thomas, Philip G Kasprzyk, Eric Ferrandis, Michel O Steinmetz, Mathew P Leese, Barry V L Potter
Quinazolinone-based anti-cancer agents were designed, decorated with functional groups from a 2-methoxyestradiol-based microtubule disruptor series, incorporating the aryl sulfamate motif of steroid sulfatase (STS) inhibitors. The steroidal AB-ring system was mimicked, favoring conformations with an N-2 substituent occupying D-ring space. Evaluation against breast and prostate tumor cell lines identified 7b with DU-145 anti-proliferative activity (GI50 300 nM). A preliminary structure-activity relationship afforded compounds (e...
December 11, 2017: Journal of Medicinal Chemistry
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