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bortezomib lymphoma

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https://www.readbyqxmd.com/read/28152955/real-world-treatment-patterns-health-care-resource-utilization-hru-and-costs-among-patients-with-waldenstrom-macroglobulinemia-wm-initiating-therapy
#1
Lorie Ellis, Stephanie Korrer, Stacey DaCosta Byfield
: 17 Background: WM is a rare, indolent B-cell lymphoma with 1000 to 1500 new cases diagnosed annually in the US. The disease is incurable with current therapy. Prior to January 2015 when ibrutinib was approved by the US FDA for WM, there were no therapies approved in this indication. This study describes initial systemic anti-cancer therapy (SACT) and HRU among WM patients (pts). METHODS: A retrospective study using a large, national US claims database from 1/2007-10/2013 was conducted...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28116786/the-combination-of-bortezomib-with-chemotherapy-to-treat%C3%A2-relapsed-refractory-acute-lymphoblastic-leukaemia-of-childhood
#2
Alice Bertaina, Luciana Vinti, Luisa Strocchio, Stefania Gaspari, Roberta Caruso, Mattia Algeri, Valentina Coletti, Carmelo Gurnari, Mariateresa Romano, Maria Giuseppina Cefalo, Katia Girardi, Valentina Trevisan, Valentina Bertaina, Pietro Merli, Franco Locatelli
Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively...
January 24, 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
#3
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/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/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#5
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/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
#6
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
#7
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/28088974/-bortezomib-rituximab-combined-with-chemotherapy-for-mantle-cell-lymphoma-two-cases-report-and-literature-review
#8
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/28076910/treatment-of-patients-with-waldenstr%C3%A3-m-macroglobulinaemia-clinical-practice-guidelines-from-the-myeloma-foundation-of-australia-medical-and-scientific-advisory-group
#9
Dipti Talaulikar, Constantine S Tam, Douglas Joshua, Joy Phoebe Ho, Jeff Szer, Hang Quach, Andrew Spencer, Simon Harrison, Peter Mollee, Andrew W Roberts, Noemi Horvath, Cindy Lee, Andrew Zannettino, Ross Brown, Bradley Augustson, Wilfrid Jaksic, John Gibson, Anna Kalff, Anna Johnston, Judith Trotman, Akash Kalro, George Grigoriadis, Chris Ward, H Miles Prince
Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM...
January 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28059091/identification-of-distinct-subgroups-of-ebv-positive-post-transplant-diffuse-large-b-cell-lymphoma
#10
Julie Morscio, Julio Finalet Ferreiro, Sara Vander Borght, Emilie Bittoun, Olivier Gheysens, Daan Dierickx, Gregor Verhoef, Iwona Wlodarska, Thomas Tousseyn
Post-transplantation lymphoproliferative disorder is an aggressive complication of transplantation, most frequently of diffuse large B-cell lymphoma morphology and associated with Epstein-Barr virus (EBV) infection/reactivation. In this study the microenvironment of EBV(+) (n=23) and EBV(-) (n=9) post-transplant non-germinal center B-cell diffuse large B-cell lymphoma was characterized. Of EBV(+) cases somatic hypermutation analysis, gene expression profiling, and extensive phenotyping were performed. Our results demonstrated variable cytotoxic T-cell infiltration and significantly increased CD163(+) M2 macrophage infiltration in EBV(+) compared with EBV(-) post-transplant diffuse large B-cell lymphoma...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28056114/diagnosis-and-management-of-waldenstr%C3%A3-m-macroglobulinemia-mayo-stratification-of-macroglobulinemia-and-risk-adapted-therapy-msmart-guidelines-2016
#11
Prashant Kapoor, Stephen M Ansell, Rafael Fonseca, Asher Chanan-Khan, Robert A Kyle, Shaji K Kumar, Joseph R Mikhael, Thomas E Witzig, Michelle Mauermann, Angela Dispenzieri, Sikander Ailawadhi, A Keith Stewart, Martha Q Lacy, Carrie A Thompson, Francis K Buadi, David Dingli, William G Morice, Ronald S Go, Dragan Jevremovic, Taimur Sher, Rebecca L King, Esteban Braggio, Ann Novak, Vivek Roy, Rhett P Ketterling, Patricia T Greipp, Martha Grogan, Ivana N Micallef, P Leif Bergsagel, Joseph P Colgan, Nelson Leung, Wilson I Gonsalves, Yi Lin, David J Inwards, Suzanne R Hayman, Grzegorz S Nowakowski, Patrick B Johnston, Steven J Russell, Svetomir N Markovic, Steven R Zeldenrust, Yi L Hwa, John A Lust, Luis F Porrata, Thomas M Habermann, S Vincent Rajkumar, Morie A Gertz, Craig B Reeder
Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations: Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course...
January 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28055975/mitotic-catastrophe-and-cell-cycle-arrest-are-alternative-cell-death-pathways-executed-by-bortezomib-in-rituximab-resistant-b-cell-lymphoma-cells
#12
Juan J Gu, Gregory P Kaufman, Cory Mavis, Myron S Czuczman, Francisco J Hernandez-Ilizaliturri
The ubiqutin-proteasome system (UPS) plays a role in rituximab-chemotherapy resistance and bortezomib (BTZ) possesses caspase-dependent (i.e. Bak stabilization) and a less characterized caspase-independent mechanism-of-action(s). Here, we define BTZ-induced caspase-independent cell death pathways. A panel of rituximab-sensitive (RSCL), rituximab-resistant cell lines (RRCL) and primary tumor cells derived from lymphoma patients (N = 13) were exposed to BTZ. Changes in cell viability, cell-cycle, senescence, and mitotic index were quantified...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28024628/polypropyleneimine-and-polyamidoamine-dendrimer-mediated-enhanced-solubilization-of-bortezomib-comparison-and-evaluation-of-mechanistic-aspects-by-thermodynamics-and-molecular-simulations
#13
Sonam Chaudhary, Avinash Gothwal, Iliyas Khan, Shubham Srivastava, Ruchi Malik, Umesh Gupta
Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28003640/induction-of-apoptosis-in-u937-cells-by-using-a-combination-of-bortezomib-and-low-intensity-ultrasound
#14
Timur Saliev, Loreto B Feril, Koichi Ogawa, Akiko Watanabe, Dinara Begimbetova, Askhat Molkenov, Dauren Alimbetov, Katsuro Tachibana
BACKGROUND We scrutinized the feasibility of apoptosis induction in blood cancer cells by means of low-intensity ultrasound and the proteasome inhibitor bortezomib (Velcade). MATERIAL AND METHODS Human leukemic monocyte lymphoma U937 cells were subjected to ultrasound in the presence of bortezomib and the echo contrast agent Sonazoid. Two types of acoustic intensity (0.18 W/cm² and 0.05 W/cm²) were used for the experiments. Treated U937 cells were analyzed for viability and levels of early and late apoptosis...
December 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27995456/current-treatment-strategies-in-relapsed-refractory-mantle-cell-lymphoma-where-are-we-now
#15
REVIEW
Erden Atilla, Pinar Ataca Atilla, Taner Demirer
The management of relapsed/refractory mantle cell lymphoma remains challenging. Patients with relapsed mantle cell lymphoma have been treated with multi-agent salvage chemotherapies; however, outcomes are poor. Although there have been studies in the relapse/refractory setting, current data indicate that autologous hematopoietic stem cell transplantation may be an especially useful approach in the front line setting in patients in first complete or partial remission following induction chemotherapy. Allogeneic hematopoietic stem cell transplantation is the only curative option, although reduced intensity conditioning in chemo-sensitive relapse or refractory mantle cell lymphoma provides better survival rates...
December 19, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27957358/bortezomib-ifosfamide-carboplatin-and-etoposide-in-a-patient-with-hiv-negative-relapsed-plasmablastic-lymphoma
#16
Mehmet Akce, Elaine Chang, Mohammad Haeri, Mike Perez, Christie J Finch, Mark M Udden, Martha P Mims
Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B cell lymphoma (DLBCL), often associated with HIV infection. We present a case of a 53-year-old HIV-negative man with untreated hepatitis C viral infection who presented with abdominal pain and lymphadenopathy. Lymph node and bone marrow biopsies were consistent with plasmablastic lymphoma. He had partial response (PR) to 6 cycles of EPOCH but disease progressed seven weeks later. Repeat biopsy was consistent with plasmablastic lymphoma. Three cycles of bortezomib, ifosfamide, carboplatin, and etoposide (B-ICE) chemotherapy resulted in a partial response (PR)...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27919179/an-analysis-of-the-role-of-follicular-lymphoma-associated-fibroblasts-to-promote-tumor-cell-viability-following-drug-induced-apoptosis
#17
Annette M Staiger, Jasmin Duppel, Michael A Dengler, Heiko van der Kuip, Matthias C Vöhringer, Walter E Aulitzky, Andreas Rosenwald, German Ott, Heike Horn
Treatment response of follicular lymphomas (FL) is highly variable. We, therefore, investigated the role of FL cancer-associated fibroblasts (CAFs) on tumor cell viability, in particular in response to treatment with cytotoxic drugs. Stromal cells outgrown from FL patients were characterized and pure CAF populations were co-cultivated with FL cells. To analyze fibroblast-mediated effects, cells in co-culture were treated with ABT-737 and Bortezomib. The adherent cell population was positive for all fibroblastic markers tested and showed increased mRNA-expression of the activation marker FAP...
December 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27917682/the-preclinical-discovery-and-development-of-bortezomib-for-the-treatment-of-mantle-cell-lymphoma
#18
Richard Arkwright, Tri Minh Pham, Jeffrey A Zonder, Q Ping Dou
Mantle cell lymphoma (MCL) is an incurable, often aggressive B-cell malignancy. Bortezomib (BTZ), the 20S proteasome inhibitor was originally developed and approved for treatment of relapsed refractory multiple myeloma, and subsequently approved for treatment of MCL. BTZ's single-agent activity induces clinical responses in approximately one-third of relapsed MCL patients. BTZ-containing combination therapies have further improved the quality and duration of clinical responses compared to standard chemotherapies in previously untreated MCL patients...
December 20, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#19
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/27903750/nuclear-export-of-ubiquitinated-proteins-determines-the-sensitivity-of-colorectal-cancer-to-proteasome-inhibitor
#20
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
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