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Sascha A Tuchman, Joseph O Moore, Carlos D DeCastro, Zhiguo Li, Emily Sellars, Yubin Kang, Gwynn Long, Cristina G Gasparetto
OBJECTIVES: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnosed MM (NDMM). MATERIALS AND METHODS: Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1...
February 27, 2017: Journal of Geriatric Oncology
Joo Hyun Kim, Won Seog Kim, Jung Yong Hong, Kung Ju Ryu, Seok Jin Kim, Chaehwa Park
Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells...
December 27, 2016: Oncotarget
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
Thomas Greuter, Martin Browne, Corina Dommann-Scherrer, Daniel Binder, Christoph Renner, Ursula Kapp
In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for >9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement)...
October 2016: Oncology Letters
Mohamed-Amine Hamouda, Arnaud Jacquel, Guillaume Robert, Alexandre Puissant, Valentine Richez, Romeo Cassel, Nina Fenouille, Sandrine Roulland, Jerome Gilleron, Emmanuel Griessinger, Alix Dubois, Beatrice Bailly-Maitre, Diogo Goncalves, Aude Mallavialle, Pascal Colosetti, Sandrine Marchetti, Martine Amiot, Patricia Gomez-Bougie, Nathalie Rochet, Marcel Deckert, Herve Avet-Loiseau, Paul Hofman, Jean-Michel Karsenti, Pierre-Yves Jeandel, Claudine Blin-Wakkach, Bertrand Nadel, Thomas Cluzeau, Kenneth C Anderson, Jean-Gabriel Fuzibet, Patrick Auberger, Frederic Luciano
Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions...
August 22, 2016: Journal of Experimental Medicine
Beth Faiman
BACKGROUND: One of the most common and inadequately managed symptoms that patients with multiple myeloma (MM) experience as a result of cancer treatment is diarrhea. Diarrhea in patients with MM often is severe enough to warrant dose reduction, delays, or discontinuation of chemotherapy. Short-term diarrhea can occur as a side effect of drugs, such as bortezomib (Velcade®) or panobinostat (Farydak®). Late-onset diarrhea from lenalidomide (Revlimid®) can occur 17-24 months after the start of therapy...
August 1, 2016: Clinical Journal of Oncology Nursing
Chong Zhao, Xin Chen, Dan Zang, Xiaoying Lan, Siyan Liao, Changshan Yang, Peiquan Zhang, Jinjie Wu, Xiaofen Li, Ningning Liu, Yuning Liao, Hongbiao Huang, Xianping Shi, Lili Jiang, Xiuhua Liu, Zhimin He, Xuejun Wang, Jinbao Liu
DNA is the well-known molecular target of current platinum-based anticancer drugs; consequently, their clinical use is severely restricted by their systemic toxicities and drug resistance originating from non-selective DNA damage. Various strategies have been developed to circumvent the shortcomings of platinum-based chemotherapy but the inherent problem remains unsolved. Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits greater and more selective cytotoxicity to multiple cancer cells than cisplatin, without showing discernible DNA damage both in vitro and in vivo...
September 15, 2016: Biochemical Pharmacology
Sarah Brown, Samantha Hinsley, Mónica Ballesteros, Sue Bourne, Paul McGarry, Debbie Sherratt, Louise Flanagan, Walter Gregory, Jamie Cavenagh, Roger Owen, Cathy Williams, Martin Kaiser, Eric Low, Kwee Yong
BACKGROUND: Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide...
2016: BMC Hematology
Man Shen, Xiao-Xia Jiang, Na An, Jia-Jia Zhang, Zhong-Xia Huang, Xin Li
OBJECTIVE: To explore the clinical features, treatment response and prognosis of multiple myeloma patients aged over 80 years. METHODS: The clinical data of 23 cases of newly diagnosed multiple myeloma aged over 80 years from February 2007 to July 2014 in our hospital were analyzed retrospectively. The median age was 82, and all the patients had at least 2 complicated diseases. Only 1 patient gave up the chemotherapy because of the poor performance status, the other 22 cases received individualized treatments...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
E Kontopodis, A Kotsakis, N Kentepozidis, K Syrigos, N Ziras, M Moutsos, G Filippa, A Mala, L Vamvakas, D Mavroudis, V Georgoulias, S Agelaki
BACKGROUND: Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin. METHODS: Chemotherapy-naïve patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m(2) i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m(2), (days 1 and 8), and cisplatin 70 mg/m(2) (day 1) in cycles of 21 days...
2016: Cancer Chemotherapy and Pharmacology
Ahmad Iskandarani, Ajaz A Bhat, Kodappully S Siveen, Kirti S Prabhu, Shilpa Kuttikrishnan, Muzammil A Khan, Roopesh Krishnankutty, Michal Kulinski, Rihab R Nasr, Ramzi M Mohammad, Shahab Uddin
BACKGROUND: Proteasome inhibitors are attractive cancer therapeutic agents because they can regulate apoptosis-related proteins. Bortezomib also known as Velcade(®), a proteasome inhibitor that has been approved by the food and drug administration for treatment of patients with multiple myeloma, and many clinical trials are ongoing to examine to the efficacy of bortezomib for the treatment of other malignancies. Bortezomib has been shown to induce apoptosis and inhibit cell growth of many cancer cells...
March 9, 2016: Journal of Translational Medicine
André S Bachmann, John Opoku-Ansah, Tannya R Ibarra-Rivera, Lisette P Yco, Sudhakar Ambadi, Christopher C Roberts, Chia-En A Chang, Michael C Pirrung
Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog...
April 15, 2016: Journal of Biological Chemistry
Sachiko Tsukamoto
Since the approval of the proteasome inhibitor, Velcade(®), by the Food and Drug Administration (FDA) for the treatment of relapsed multiple myeloma, inhibitors of the ubiquitin-proteasome system have been attracting increasing attention as promising drug leads for cancer therapy. While the development of drugs for diseases related to this proteolytic system has mainly been achieved by searching libraries of synthetic small molecules or chemical modifications to drug leads, limited searches have been conducted on natural sources...
2016: Chemical & Pharmaceutical Bulletin
Brittany C Lipchick, Emily E Fink, Mikhail A Nikiforov
Multiple myeloma is a form of plasma cell neoplasm that accounts for approximately 10% of all hematological malignancies. Recently, several novel drugs have been discovered that almost doubled the overall survival of multiple myeloma patients. One of these drugs, the first-in-class proteasome inhibitor bortezomib (Velcade) has demonstrated remarkable response rates in multiple myeloma patients, and yet, currently this disease remains incurable. The major factor undermining the success of multiple myeloma treatment is a rapidly emerging resistance to the available therapy...
March 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ka C Lee, Rebecca L Bramley, Ian G Cowell, Graham H Jackson, Caroline A Austin
The reaction mechanism of DNA topoisomerase II (TOP2) involves a covalent double-strand break intermediate in which the enzyme is coupled to DNA via a 5'-phosphotyrosyl bond. This normally transient enzyme-bridged break is stabilised by drugs such as mitoxantrone, mAMSA, etoposide, doxorubicin, epirubicin and idarubicin, which are referred to as TOP2 poisons. Removal of topoisomerase II by the proteasome is involved in the repair of these lesions. In K562 cells, inhibiting the proteasome with MG132 significantly potentiated the growth inhibition by these six drugs that target topoisomerase II, and the highest level of potentiation was observed with mitoxantrone...
March 1, 2016: Biochemical Pharmacology
Lili Gao, Qinlu Li, Jinsong Kang, Chunrui Li, Jianfeng Zhou
We report a case of a woman, who initially presented with an non-secreting multiple myeloma, 11 months later, she was diagnosed as an IgD-secreting myeloma. In December, 2010, the patient's serum protein quantification and immunofixation electrophoresis (IFE) revealed polyclonal immunoglobulin with no evidence of monoclonal immunoglobulin. However, her bone marrow smears revealed an abnormal proliferation of atypical plasma cells (46.5%), so she was diagnosed as non-secreting multiple myeloma. After three cycles of administration of Velcade plus Dexamethasone (VD), she achieved a complete remission (CR)...
2015: International Journal of Clinical and Experimental Medicine
Amit Kumar Tyagi, Sahdeo Prasad, Wei Yuan, Shiyou Li, Bharat B Aggarwal
Considering that as many as 80% of the anticancer drugs have their roots in natural products derived from traditional medicine, we examined compounds other than curcumin from turmeric (Curcuma longa) that could exhibit anticancer potential. Present study describes the isolation and characterization of another turmeric-derived compound, β-sesquiphellandrene (SQP) that exhibits anticancer potential comparable to that of curcumin. We isolated several compounds from turmeric, including SQP, α-curcumene, ar-turmerone, α-turmerone, β-turmerone, and γ-turmerone, only SQP was found to have antiproliferative effects comparable to those of curcumin in human leukemia, multiple myeloma, and colorectal cancer cells...
December 2015: Investigational New Drugs
Lauren Tada, Humayun Anjum, W Kenneth Linville, Salim Surani
Recurrent pleural effusions occurring in association with immunoglobulin light chain amyloidosis and not associated with amyloid cardiomyopathy are rare. These portend an overall poor prognosis with mean survival time of approximately 1.8 months. We hereby report a case of a 59-year-old Caucasian female with recurrent pleural effusions and an ultimate diagnosis of pulmonary amyloidosis in association with plasma cell myeloma. The optimal treatment for recurrent pleural effusions in amyloidosis has not been determined; however, our patient responded to therapy with Cyclophosphamide-Bortezomib- (Velcade-) Dexamethasone (CyBorD) and had no repeat hospitalizations or recurrence of pleural effusion at four-month follow-up after initiation of therapy...
2015: Case Reports in Pulmonology
Chao-Yang Lai, Da-Wei Yeh, Chih-Hao Lu, Yi-Ling Liu, Li-Rung Huang, Cheng-Yuan Kao, Huan-Yuan Chen, Chi-Ying F Huang, Chung-Hsing Chang, Yunping Luo, Rong Xiang, Tsung-Hsien Chuang
Activation of TLR7-9 has been linked to the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Thus, therapeutic applications of antagonists of these TLRs for such disorders are being investigated. Bortezomib (Velcade) is a proteasome inhibitor known to suppress activation of these TLRs. To identify novel TLR7-9 inhibitors, we searched the Gene Expression Omnibus database for gene expression profiles of bortezomib-treated cells. These profiles were then used to screen the Connectivity Map database for chemical compounds with similar functions as bortezomib...
October 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
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