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https://www.readbyqxmd.com/read/29070146/-research-progress-on-molecular-mechanisms-of-resistance-to-bortezomib-in-multiple-myeloma-review
#1
Ling-Ling Shi, Yong-Ping Zhai
Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29056470/phase-2-open-label-study-of-bortezomib-cladribine-and-rituximab-in-advanced-newly-diagnosed-and-relapsed-refractory-mantle-cell-and-indolent-lymphomas
#2
Soham D Puvvada, José Guillen-Rodriguez, Abhijeet Kumar, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Jonathan H Schatz, Daruka Mahadevan, Daniel O Persky
BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29026157/bortezomib-promotes-khsv-and-ebv-lytic-cycle-by-activating-jnk-and-autophagy
#3
Marisa Granato, Maria Anele Romeo, Mariangela Sara Tiano, Roberta Santarelli, Roberta Gonnella, Maria Saveria Gilardini Montani, Alberto Faggioni, Mara Cirone
KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, the few cells that undergo viral replication may contribute to the pathogenesis and maintenance of the virus-associated malignancies. Cytotoxic drugs used for the therapies of cancers harboring virus-infection often have, as side effect, the activation of viral lytic cycle. Therefore it is important to investigate whether they affect viral reactivation and understand the underlying mechanisms involved...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993364/durable-complete-remission-with-combination-chemotherapy-and-bortezomib-in-hiv-associated-plasmablastic-lymphoma
#4
Nivedita Arora, Arjun Gupta, Navid Sadeghi
Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states such as transplant recipients, autoimmune diseases and the elderly. PBL is generally associated with a poor prognosis despite chemotherapy. There is evidence supporting the use of bortezomib in combination with standard chemotherapy to achieve durable responses in patients with PBL. We describe a patient with acquired immunodeficiency syndrome who presented with rectal pain and bright red blood per rectum...
October 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28978845/treatment-for-mantle-cell-lymphoma
#5
Koji Izutsu
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by CD5+, CCND1+, and the CCND1-IGH translocation. Although patients with MCL respond, at least temporarily, to conventional chemotherapy, they eventually have a relapse and the prognosis is generally poor. As a primary treatment option for patients with untreated MCL, a rituximab-containing chemotherapy regimen is administered according to the patient's eligibility for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28964970/metformin-triggers-apoptosis-in-pel-cells-and-alters-bortezomib-induced-unfolded-protein-response-increasing-its-cytotoxicity-and-inhibiting-kshv-lytic-cycle-activation
#6
Marisa Granato, Maria Saveria Gilardini Montani, Maria Anele Romeo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Metformin, the most used drug for the treatment of diabetes type 2 patients, has been shown to have anti-cancer properties. In this study, we found that metformin induced apoptosis in Primary Effusion Lymphoma (PEL) cells, an aggressive B cell lymphoma associated with KSHV against which the conventional therapies usually fail. The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28963907/bortezomib-in-plasmablastic-lymphoma-a-glimpse-of-hope-for-a-hard-to-treat-disease
#7
REVIEW
Thomas A Guerrero-Garcia, Renzo J Mogollon, Jorge J Castillo
Plasmablastic lymphoma (PBL) is a rare and hard to treat disease. With current standard chemotherapeutic regimens, PBL is associated with a median overall survival of 12-15 months. We performed a systematic review of the literature through March 31, 2017 looking for patients with a diagnosis of PBL who were treated with bortezomib, alone or in combination. We identified 21 patients, of which 11 received bortezomib in the frontline setting and 10 received bortezomib in the relapsed setting. Eleven patients were HIV-positive and 10 were HIV-negative...
November 2017: Leukemia Research
https://www.readbyqxmd.com/read/28932850/amino-and-chloro-8-hydroxyquinolines-and-their-copper-complexes-as-proteasome-inhibitors-and-antiproliferative-agents
#8
Valentina Oliveri, Valeria Lanza, Danilo Milardi, Maurizio Viale, Irena Maric, Carmelo Sgarlata, Graziella Vecchio
Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents. The approval of the proteasome inhibitor drug bortezomib for the treatment of myeloma and lymphoma further highlights the need for UPS inhibitors...
October 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28923647/is-cytomegalovirus-surveillance-necessary-for-patients-with-low-reactivation-risk-in-an-autologous-hematopoietic-cell-transplantation-setting
#9
A H Kaya, E Tekgunduz, S Akpinar, H Batgi, F Bekdemir, O Kayikci, S Namdaroglu, B U Ulu, M S Dal, M K Cakar, S Korkmaz, F Altuntas
BACKGROUND: In an autologous hematopoietic cell transplantation (AHCT) setting, routine cytomegalovirus (CMV) surveillance is not indicated except in high-risk situations. On the other hand, some studies reported increased CMV reactivation in AHCT setting as a result of incorporation of novel agents into treatment algorithms, such as bortezomib and rituximab. We retrospectively analyzed CMV reactivation and infection rates in patients with no high-risk features, who were treated with AHCT...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28871325/high-level-of-soluble-interleukin-2-receptor-in-serum-predicts-treatment-resistance-and-poor-progression-free-survival-in-multiple-myeloma
#10
Liang Wang, Jing-Hua Wang, Wen-Jian Liu, Wei-da Wang, Hua Wang, Xiao-Qin Chen, Qi-Rong Geng, Yue Lu, Zhong-Jun Xia
The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM...
September 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28862883/randomized-phase-ii-study-of-r-chop-with-or-without-bortezomib-in-previously-untreated-patients-with-non-germinal-center-b-cell-like-diffuse-large-b-cell-lymphoma
#11
RANDOMIZED CONTROLLED TRIAL
John P Leonard, Kathryn S Kolibaba, James A Reeves, Anil Tulpule, Ian W Flinn, Tatjana Kolevska, Robert Robles, Christopher R Flowers, Robert Collins, Nicholas J DiBella, Steven W Papish, Parameswaran Venugopal, Andrew Horodner, Amir Tabatabai, Julio Hajdenberg, Jaehong Park, Rachel Neuwirth, George Mulligan, Kaveri Suryanarayan, Dixie-Lee Esseltine, Sven de Vos
Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1...
November 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28858138/model-based-meta-analysis-of-progression-free-survival-in-non-hodgkin-lymphoma-patients
#12
REVIEW
Mengyao Li, Nimita Dave, Ahmed Hamed Salem, Kevin J Freise
BACKGROUND: Non-Hodgkin lymphoma (NHL) is a group of lymphoproliferative malignancies with varying treatment responses and progression-free survival (PFS) times. The objective of this study was to quantify the effect of treatment and patient-population characteristics on PFS in patients with NHL. METHODS: A database was developed from 513 NHL clinical trials reported from 1993 to 2015. Summary-level PFS was obtained from 112 of these trials, which included 155 cohorts and 11,824 patients...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28856001/bortezomib-as-a-probable-cause-of-the-syndrome-of-inappropriate-antidiuretic-hormone-secretion-a-case-report-and-review-of-the-literature
#13
Cheng-Lan Lv, Juan Li
Bortezomib is a proteasome inhibitor that has been widely adopted for the treatment of hematological malignancies, including multiple myeloma and lymphoma, and has been considered significantly more tolerable compared with traditional chemotherapeutic drugs. Bortezomib has some potential side effects that involve a number of systems, including the gastrointestinal, hematological, nervous and musculoskeletal systems; however, involvement of the endocrine system is rare. We herein report the case of a patient treated for multiple myeloma who developed the syndrome of inappropriate antidiuretic hormone secretion after bortezomib was added to his chemotherapy regimen...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28855986/treatment-of-relapsed-extranodal-natural-killer-t-cell-lymphoma-with-bortezomib-plus-fludarabine
#14
Chen Chen, Hongmin He
Extranodal NK/T cell lymphoma (ENKL) is a rare entity, associated with an aggressive clinical behavior and poor prognosis. The optimal treatment strategies, particularly for relapsed patients, have not been clearly determined. A 40-year-old female ENKL patient with orbital involvement as the first presentation was initially suspected to have an orbital pseudotumor. When the patient developed disease progression following treatment with methylprednisolone, biopsy of the orbital mass was performed. Histopathological examination of the biopsy specimen was consistent with the diagnosis of ENKL (Ann Arbor stage IE)...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#15
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28733196/proteasome-subunit-beta-type-1-p11a-polymorphism-is-a-new-prognostic-marker-in-multiple-myeloma
#16
Gergely Varga, Gábor Mikala, Katalin Piroska Kiss, Éva Kosóczki, Edit Szabó, Nóra Meggyesi, Katalin Balassa, Petra Kövy, Bálint Tegze, Gergely Szombath, Attila Tordai, Hajnalka Andrikovics, László Homolya, Tamás Masszi
BACKGROUND: Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma. PATIENTS AND METHODS: We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences. RESULTS: On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28716527/identification-of-a-synergistic-combination-of-smac-mimetic-and-bortezomib-to-trigger-cell-death-in-b-cell-non-hodgkin-lymphoma-cells
#17
Irfan Ahmed Bhatti, Behnaz Ahangarian Abhari, Simone Fulda
Recently, copy number gains and increased expression levels of cIAP1 and cIAP2 have been reported in B-cell non-Hodgkin lymphomas (NHL). Therefore, we investigated the therapeutic potential of the Smac mimetic BV6 that antagonizes cIAP1/2 and XIAP. Here, we discover that subtoxic concentrations of BV6 prime B-cell NHL cells to proteasome inhibitor Bortezomib-induced cell death. Synergistic induction of cell death by BV6 and Bortezomib is confirmed by calculation of combination index in different cell lines, emphasizing the broader relevance of this combination...
October 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28699667/mantle-cell-lymphoma-2017-update-on-diagnosis-risk-stratification-and-clinical-management
#18
REVIEW
Julie M Vose
DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28699256/long-term-analysis-of-phase-ii-studies-of-single-agent-lenalidomide-in-relapsed-refractory-mantle-cell-lymphoma
#19
MULTICENTER STUDY
Thomas E Witzig, Pier Luigi Zinzani, Thomas M Habermann, Joseph M Tuscano, Johannes Drach, Radhakrishnan Ramchandren, Sevgi Kalayoglu Besisik, Kenichi Takeshita, Marie-Laure Casadebaig Bravo, Lei Zhang, Tommy Fu, Andre Goy
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide longer follow-up on the MCL-001 study (follow-ups were 6...
October 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28696812/a-phase-i-trial-of-bortezomib-in-combination-with-everolimus-for-treatment-of-relapsed-refractory-non-hodgkin-lymphoma
#20
Brian T Hill, Mitchell R Smith, Meredeth Shelley, Deepa Jagadeesh, Robert M Dean, Brad Pohlman, John W Sweetenham, Brian J Bolwell, Stephen D Smith
B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1...
July 11, 2017: Leukemia & Lymphoma
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