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https://www.readbyqxmd.com/read/28107546/bone-marrow-stroma-protects-myeloma-cells-from-cytotoxic-damage-via-induction-of-the-oncoprotein-muc1
#1
Michal Bar-Natan, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Arie Apel, Hasan Rajabi, Athalia R Pyzer, Kristen Palmer, Michaela R Reagan, Myrna R Nahas, Rebecca Karp Leaf, Salvia Jain, Jon Arnason, Irene M Ghobrial, Kenneth C Anderson, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is a lethal haematological malignancy that arises in the context of a tumour microenvironment that promotes resistance to apoptosis and immune escape. In the present study, we demonstrate that co-culture of MM cells with stromal cells results in increased resistance to cytotoxic and biological agents as manifested by decreased rates of cell death following exposure to alkylating agents and the proteosome inhibitor, bortezomib. To identify the mechanism of increased resistance, we examined the effect of the co-culture of MM cells with stroma cells, on expression of the MUC1 oncogene, known to confer tumour cells with resistance to apoptosis and necrosis...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28107479/apoptosis-induction-and-gene-expression-profile-alterations-of-cutaneous-t-cell-lymphoma-cells-following-their-exposure-to-bortezomib-and-methotrexate
#2
Vassiliki Mpakou, Evangelia Papadavid, Frieda Kontsioti, Eugene Konsta, Miriam Vikentiou, Aris Spathis, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Efthimia Mpazani, Petros Karakitsos, Dimitrios Rigopoulos, George Dimitriadis, Vasiliki Pappa
Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL's resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF...
2017: PloS One
https://www.readbyqxmd.com/read/28105211/diagnostic-and-therapeutic-approaches-to-multiple-myeloma-patients-real-world-data-from-representative-multicentre-treatment-surveys-in-germany-between-2008-and-2011
#3
Thomas M Moehler, Maximilian Merz, Lenka Kellermann, Hartmut Goldschmidt, Wolfgang Knauf
A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28103725/a-phase-1-study-of-bortezomib-and-romidepsin-in-patients-with-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-indolent-b-cell-lymphoma-peripheral-t-cell-lymphoma-or-cutaneous-t-cell-lymphoma
#4
Beata Holkova, Victor Yazbeck, Maciej Kmieciak, Prithviraj Bose, Shuo Ma, Amy Kimball, Mary Beth Tombes, Ellen Shrader, Wen Wan, Caryn Weir-Wiggins, Amanda Singh, Kevin T Hogan, Sarah Conine, Heidi Sankala, John D Roberts, Thomas C Shea, Steven Grant
A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m(2) bortezomib and 10 mg/m(2) romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease...
January 19, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#5
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/28101022/necrobiotic-xanthogranuloma-in-a-patient-with-multiple-myeloma
#6
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/28099937/inactivation-of-ck1%C3%AE-in-multiple-myeloma-empowers-drug-cytotoxicity-by-affecting-akt-and-%C3%AE-catenin-survival-signaling-pathways
#7
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
#8
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/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#9
Morie A Gertz
: Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28093826/highly-sensitive-detection-of-e2-activity-in-ubiquitination-using-an-artificial-ring-finger
#10
Kazuhide Miyamoto, Miho Sumida, Mayumi Yuasa-Sunagawa, Kazuki Saito
The ubiquitin-conjugating (E2) enzymes of protein ubiquitination are associated with various diseases such as leukemia, lung cancer, and breast cancer. Rapid and accurate detection of E2 enzymatic activities remains poor. Here, we described the detection of E2 activity on a signal accumulation ISFET biosensor (AMIS sensor) using an artificial RING finger (ARF). The use of ARF enables the simplified detection of E2 activity without a substrate. The high-sensitivity quantitative detection of E2 activities was demonstrated via real-time monitoring over a response range of femtomolar to micromolar concentrations...
January 17, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28092998/treatment-patterns-and-outcomes-with-subcutaneous-bortezomib-in-patients-with-relapsed-mantle-cell-lymphoma-a-retrospective-observational-study-of-patient-medical-records-from-us-community-oncology-practices
#11
Alan P Skarbnik, Esprit Ma, Marie-Hélène Lafeuille, Jonathan Fortier, Tatyana Feldman, Mei Sheng Duh, Helgi van de Velde, Liviu Niculescu, Vijayveer Bonthapally, André Goy
No abstract text is available yet for this article.
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#12
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28092421/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-heavily-pretreated-multiple-myeloma-a-phase-1-study-in-japan
#13
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/28092129/bortezomib-in-the-treatment-of-antibody-mediated-rejection-in-pediatric-kidney-transplant-recipients-a-multicenter-midwest-pediatric-nephrology-consortium-study
#14
Sarah Kizilbash, Donna Claes, Isa Ashoor, Ashton Chen, Sara Jandeska, Raed Bou Matar, Jason Misurac, Joseph Sherbotie, Katherine Twombley, Priya Verghese
Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients...
January 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28091419/two-secondary-primary-malignancies-after-bortezomib-therapy-for-multiple-myeloma-a-single-center-experience
#15
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/28088974/-bortezomib-rituximab-combined-with-chemotherapy-for-mantle-cell-lymphoma-two-cases-report-and-literature-review
#16
J Su, H Xu, X Shi, X F Sui, Z G Cui, H G Zhao
No abstract text is available yet for this article.
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#17
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087006/new-insights-into-the-pathogenesis-and-treatment-of-heavy-chain-deposition-disease
#18
Jonathan J Hogan, Glen S Markowitz
Heavy chain deposition disease is defined by the presence of tissue deposits of truncated monoclonal Ig heavy chains, usually associated with an underlying plasma cell clone. In this issue of Kidney International, Bridoux et al. described the clinical, histologic, and molecular characterization of 15 patients with heavy chain deposition disease, which is the largest case series to date. Notable findings included the frequent presence of C3 deposits and hypocomplementemia, the uniform finding of truncated heavy chains with the deletion in the heavy chain constant region 1, and the common occurrence of an abnormal serum-free κ:λ ratio, despite the absence of light-chain tissue deposition...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28081343/the-combined-effects-of-proteasome-inhibitor-bortezomib-with-topoisomerase-i-and-ii-inhibitors-on-topoisomerase-enzymes
#19
Emine Öksüzoğlu, Çiydem Tırınoğlu, Barış Kerimoğlu
BACKGROUND/AIM: DNA topoisomerases are ubiquitous enzymes that regulate conformational changes in DNA topology during essential cellular processes, and, for this reason, have been characterized as the cellular targets of a number of anticancer drugs. Bortezomib is a powerful proteasome inhibitor used in the treatment of hematological malignancies. In this study, we investigated the inhibitory effects of bortezomib on human topoisomerase I and II enzymes both alone and in combination modes with camptothecin and etoposide...
December 20, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28079515/efficacy-and-safety-of-subcutaneous-versus-intravenous-bortezomib-in-multiple-myeloma-a%C3%A2-meta-analysis%C3%A2
#20
Bin Hu, Quan Zhou, Tao Wu, Lan Zhuang, Liping Yi, Jinxia Cao, Xin Yang, Jun Wang
PURPOSE: We performed this meta-analysis to compare the efficacy and safety between two different administration routes of bortezomib, subcutaneous and intravenous. METHODS: Six retrospective studies and three randomized controlled trials (RCTs) were included in our study. Data from retrospective studies or RCTs were pooled and displayed in their corresponding subgroup, retrospective studies subgroup or RCTs subgroup. We comprehensively compared the overall response rate (ORR) and the incidence of adverse events between subcutaneous and intravenous bortezomib...
January 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
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