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bortezomib lymphoma

Dharshan Sivaraj, Michael M Green, Cristina Gasparetto
Multiple myeloma (MM) is the second most common blood cancer following non-Hodgkin's lymphoma. While the treatments for MM have improved over the past decade, for the most part, it remains an incurable disease. For this reason newer therapeutic agents are needed to combat this malignancy. Panobinostat is a pan-deacetylase inhibitor that impedes protein destruction by disturbing the enzymatic activity of deacetylases. It was US FDA approved in February 2015 for the management of relapsed/refractory MM in combination with bortezomib and dexamethasone...
October 25, 2016: Future Oncology
J J Wen, Z B Liu, C G Xu
Objective: To determine the anti-tumor effects of 13-cis-retinoic acid (13cRA) combined with interferonα-2b (IFNα-2b) in mantle cell lymphoma (MCL) animal model. Methods: The animal model of MCL was established by introducing Jeko-1 cell line into severe combined immunodeficiency disease mice. The successfully tumor-developed mice were assigned to different groups treated with negative control group (solvents), 13cRA (high dose: 200mg/kg; middle dose: 100mg/kg; low dose: 50 mg/kg) alone, IFNα-2b alone or combination of different dose of 13cRA with IFNα-2b, and positive control group (bortezomib, rituximab, cyclophosphamide), respectively...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Kensuke Kojima, Aya Maeda, Mariko Yoshimura, Yuki Nishida, Shinya Kimura
PPM1D is a serine/threonine phosphatase that negatively regulates key DNA damage response proteins, such as p53, p38 MAPK, histone H2A.X, and ATM. We investigated the pathophysiological significance of PPM1D and its therapeutic targeting by the novel PPM1D inhibitor GSK2830371 in mantle cell lymphoma (MCL). Oncomine-based analyses indicated increased PPM1D mRNA levels in MCL cells compared with their normal counterpart cells. Higher PPM1D expression was associated with higher expression of the proliferation gene signature and poorer prognosis in patients...
September 8, 2016: Oncotarget
Yusuke Koizumi, Tomoko Uehira, Yasunori Ota, Yoshihiko Ogawa, Keishiro Yajima, Junko Tanuma, Mihoko Yotsumoto, Shotaro Hagiwara, Satoshi Ikegaya, Dai Watanabe, Hitoshi Minamiguchi, Keiko Hodohara, Kenta Murotani, Hiroshige Mikamo, Hideho Wada, Atsushi Ajisawa, Takuma Shirasaka, Hirokazu Nagai, Yoshinori Kodama, Tsunekazu Hishima, Makoto Mochizuki, Harutaka Katano, Seiji Okada
Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites...
September 7, 2016: International Journal of Hematology
Yoichi Imai, Yoshiro Maru, Junji Tanaka
Histone deacetylases (HDACs) critically regulate gene expression by determining the acetylation status of histones. In addition, studies have increasingly focused on the activities of HDACs, especially involving non-histone proteins, and their various biological effects. Aberrant HDAC expression observed in several kinds of human tumors makes HDACs potential targets for cancer treatment. Several preclinical studies have suggested that HDAC inhibitors exhibit some efficacy in the treatment of acute myelogenous leukemia (AML) with AML1-ETO, which mediates transcriptional repression through its interaction with a complex including HDAC1...
August 24, 2016: Cancer Science
Marc Sorigue, Josep-Maria Ribera, Cristina Motlló, Juan-Manuel Sancho
Despite the improvement in prognosis since the advent of rituximab, follicular lymphoma is still incurable and remains the cause of death of most afflicted patients. With the expanding knowledge of the pathogenesis of B-cell malignancies, in the last few years a plethora of new therapies acting through a variety of mechanisms have shown promising results. This review attempts to analyze the evidence available on these new drugs, which include new monoclonal antibodies and immunoconjugates, the anti-angiogenic and immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, inhibitors of B-cell receptor pathway enzymes, such as ibrutinib, idelalisib, duvelisib and entospletinib, BCL2 inhibitors and checkpoint inhibitors...
October 2016: Leukemia Research
Bryan Hambley, Paolo F Caimi, Basem M William
Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents...
August 2016: Therapeutic Advances in Hematology
Marjolijn van Keep, Kerry Gairy, Divyagiri Seshagiri, Pushpike Thilakarathne, Dawn Lee
BACKGROUND: Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin's lymphoma. Bortezomib is the first product to be approved for the treatment of patients with previously untreated MCL, for whom haematopoietic stem cell transplantation is unsuitable, and is used in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP). The National Institute of Health and Care Excellence recently recommended the use of VR-CAP in the UK following a technology appraisal...
2016: BMC Cancer
Adam J Olszewski, Steven P Treon, Jorge J Castillo
INTRODUCTION: Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community. METHOD: We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data...
July 29, 2016: Oncologist
Rebecca Citrin, Jessica B Foster, David T Teachey
INTRODUCTION: Proteasome inhibitors have garnered interest as novel chemotherapeutic agents based on their ability to inhibit the growth of cancer cells by altering the balance of intracellular proteins. Initial clinical trials of this drug class focused on bortezomib, a reversible inhibitor of the 20S proteasome, with promising results for the treatment of adult hematologic malignancies, including multiple myeloma and non-Hodgkin lymphoma. AREAS COVERED: This article will review the use of bortezomib and other proteasome inhibitors in both adult and pediatric populations, with a focus on their use in pediatrics...
September 2016: Expert Review of Hematology
Jun Zhang, Wenju Lu, Yuqin Chen, Qian Jiang, Kai Yang, Meichan Li, Ziyi Wang, Xin Duan, Lei Xu, Haiyang Tang, Dejun Sun, Jian Wang
The ubiquitin-proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling...
September 1, 2016: American Journal of Physiology. Cell Physiology
Prabhashankar Mishra, Smriti Kakri, Sumeet Gujral
Plasmablastic lymphoma (PBL) can rarely be seen as a transformation from plasma cell myeloma (PCM), especially in late stages of the disease where it portends a poorer prognosis and a different line of management for the patient. When unrelated to PCM, PBL is considered to be a separate aggressive variant of B-cell lymphoma typically seen in the oral cavity of immunocompromised adults. We describe a case of plasmablastic transformation having a pan T-cell phenotype with CD3 and CD4 positivity, in an immunocompetent elderly lady diagnosed with PCM...
June 30, 2016: Acta Clinica Belgica
Seung-Shin Lee, Sung-Hoon Jung, Jae-Sook Ahn, Yeo-Kyeoung Kim, Min-Seok Cho, Seung-Yeon Jung, Je-Jung Lee, Hyeoung-Joon Kim, Deok-Hwan Yang
Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle...
July 2016: Journal of Korean Medical Science
Erich Balsman
Bortezomib was the first antineoplastic proteasome inhibitor and is currently indicated for the treatment of hematologic malignancies including multiple myeloma and mantle cell lymphoma. This report describes a 57-year-old patient with light chain (primary) amyloidosis receiving weekly subcutaneous bortezomib injections who presented with recurrent hypoxemia and interstitial pneumonitis. Following the failure of conventional therapy, the patient responded rapidly to high-dose intravenous methylprednisolone...
June 29, 2016: Journal of Oncology Pharmacy Practice
Emanuele Cencini, Susanna Guerrini, Maria Antonietta Mazzei, Annalisa Chiappella, Alberto Fabbri
Relapsed mantle cell lymphoma (MCL) usually represents a hard challenge, especially after the failure of high-dose therapy or in elderly patients, and although new agents have been investigated, responses are often short and a significant proportion of patients finally die from progressive disease. Here, we report a case of a relapsed MCL patient that achieved durable response with bortezomib and rituximab. Treatment regimen consisted of bortezomib 1.6 mg/m(2) and rituximab 375 mg/m(2) intravenously on days 1-8-15-22 for the 1st course, followed by 2 courses of bortezomib with the same schedule...
October 2016: Journal of Chemotherapy
Maryam Delforoush, Mattias Berglund, Per-Henrik Edqvist, Christer Sundström, Joachim Gullbo, Gunilla Enblad
OBJECTIVES: Investigating expression of possible targets for proteasome inhibitors in patients with diffuse large B-cell lymphoma (DLBCL) and correlating the findings to clinical parameters and outcome. METHODS: Tumour material from 92 patients with DLBCL treated with either R-CHOP like (n = 69) or CHOP like (n = 23) regimens were stained for possible targets of proteasome inhibitors. RESULTS: The primary target molecule of bortezomib, proteasome subunit beta, type 5 (PSMB5), was not detected in the tumour cells in any of the cases but showed an abundant expression in cells in the microenvironment...
June 14, 2016: European Journal of Haematology
Katy Mastorci, Barbara Montico, Damiana A Faè, Luca Sigalotti, Maurilio Ponzoni, Giorgio Inghirami, Riccardo Dolcetti, Jessica Dal Col
Mantle cell lymphoma (MCL) is an aggressive haematological malignancy in which the response to therapy can be limited by aberrantly activated molecular and cellular pathways, among which autophagy was recently listed. Our study shows that the 9-cis-retinoic acid (RA)/Interferon(IFN)-α combination induces protective autophagy in MCL cell lines and primary cultures reducing the extent of drug-induced apoptosis. The treatment significantly up-regulates phospholipid scramblase 1 (PLSCR1), a protein which bi-directionally flips lipids across membranes...
May 26, 2016: Oncotarget
Ehsan Malek, James J Driscoll
Multiple myeloma (MM) remains an incurable plasma cell malignancy and drug resistance persists as the major cause of treatment failure leading to fatal outcomes. The phosphatidyl-inositol-3-kinase (PI3K) pathway is constitutively hyperactivated in MM to promote disease progression and drug resistance. While inhibiting PI3K induces apoptosis in MM and is predicted to increase tumor susceptibility to anticancer therapy, early-generation pan-PI3K inhibitors display poor clinical efficacy as well as intolerable side effects...
May 24, 2016: Oncotarget
Jeremy T Larsen, Shaji Kumar
Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone marrow plasma cell ≥60%, involved:uninvolved serum free light chain ratio ≥100, or >1 focal lesion on magnetic resonance imaging) to identify near inevitable progression to symptomatic MM requiring therapy...
2015: Rare Cancers and Therapy
Meng Lei, Huayun Feng, Cheng Wang, Hailing Li, Jingmiao Shi, Jia Wang, Zhaogang Liu, Shanshan Chen, Shihe Hu, Yongqiang Zhu
Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized...
June 1, 2016: Bioorganic & Medicinal Chemistry
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