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https://www.readbyqxmd.com/read/28531943/recent-trends-in-zikv-research-a-step-away-from-cure
#1
REVIEW
Aftab Alam, Nikhat Imam, Anam Farooqui, Shahnawaz Ali, Md Zubbair Malik, Romana Ishrat
Zika virus (ZikV) is a member of the Flaviviridae virus family, genus Flavivirus has emerged as a potential threat to human health worldwide. Consequences of vertical infections includes microcephaly with brain and eye anomalies, and adult infections includes Guillain-Barrésyndrome (GBS), brain ischemia, myelitis and meningoencephalitis. To develop a better treatment, many efforts are being made, like drug-repurposing concept for FDA-approved drugs for antiviral activity are screened against ZikV infection and emerging as a promising alternative to expedite drug development and various vaccines like DNA, ZPIV, LAIV, mRNA and AGS-v vaccines have been designed and in under clinical trial phases...
May 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531181/weekly-versus-biweekly-bortezomib-given-in-patients-with-indolent-non-hodgkin-lymphoma-a-meta-analysis
#2
Ting Yuan, Feng Zhang, Qing-Min Yao, Yan-Xia Liu, Xiao-Juan Zhu, Xin Wang
BACKGROUND: Bortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain. METHODS: We did a systematic review and meta-analysis of the clinical trials comparing the efficacy and toxicity of the weekly and biweekly schedules of bortezomib in patients with indolent lymphoma. We searched Pubmed, Cochrane Library and Emabase from inception to July 29, 2016. The primary outcome was the overall response rate including the complete response rate and the partial response rate...
2017: PloS One
https://www.readbyqxmd.com/read/28524233/bortezomib-sensitizes-human-osteosarcoma-cells-to-adriamycin-induced-apoptosis-through-ros-dependent-activation-of-p-eif2%C3%AE-atf4-chop-axis
#3
Miao Xian, Handi Cao, Ji Cao, Xuejing Shao, Difeng Zhu, Ning Zhang, Ping Huang, Weixu Li, Bo Yang, Meidan Ying, Qiaojun He
Osteosarcoma is the most common bone cancer, and chemotherapy is currently indispensable for its treatment. Adriamycin has been claimed to be the most effective agent for osteosarcoma, however, the outcome of adriamycin chemotherapy remains unsatisfactory. Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed that the activation of p-eIF2α/ATF4/CHOP axis is the underlying associated mechanisms...
May 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28522110/high-dose-gemcitabine-busulfan-and-melphalan-for-autologous-stem-cell-transplant-in-patients-with-relapsed-or-refractory-myeloma-a-phase-2-trial-and-matched-pair-comparison-with-melphalan
#4
Yago Nieto, Benigno C Valdez, Sai R Pingali, Roland Bassett, Ruby Delgado, John Nguyen, Nina Shah, Uday Popat, Roy B Jones, Borje S Andersson, Alison Gulbis, Sairah Ahmed, Qaiser Bashir, Simrit Parmar, Krina Patel, Alan Myers, Gabriela Rondon, Robert Z Orlowski, Richard Champlin, Muzaffar Qazilbash
BACKGROUND: High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan. METHODS: We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT...
May 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28521480/clinical-effect-of-immunophenotyping-on-the-prognosis-of-multiple-myeloma-patients-treated-with-bortezomib
#5
Noriyoshi Iriyama, Katsuhiro Miura, Yoshihiro Hatta, Sumiko Kobayashi, Yoshihito Uchino, Daisuke Kurita, Hitomi Sakagami, Hiromichi Takahashi, Masashi Sakagami, Yujin Kobayashi, Masaru Nakagawa, Shimon Ohtake, Yoshikazu Iizuka, Masami Takei
In the present study, the effect of immunophenotyping on the prognoses of patients with multiple myeloma (MM) treated with bortezomib plus dexamethasone was investigated. The study involved 46 patients with MM, and analyzed the prognostic significance of the expression of cluster of differentiation (CD)45, CD56 and mature plasma cell (MPC)-1, and other factors including the International Staging System (ISS) stage, age, gender, the immunoglobulin subtype and the treatment line number prior to bortezomib treatment...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520213/the-pnpla3-variant-associated-with-fatty-liver-disease-i148m-accumulates-on-lipid-droplets-by-evading-ubiquitylation
#6
Soumik BasuRay, Eriks Smagris, Jonathan C Cohen, Helen H Hobbs
A sequence variation (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is strongly associated with fatty liver disease (FLD), but the underlying mechanism remains obscure. Here we used knock-in (KI) mice (Pnpla3(148M/M) ) to examine the mechanism responsible for accumulation of triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were found between Pnpla3(148M/M) and Pnpla3(+/+) mice in hepatic TG synthesis, utilization, or secretion. These results are consistent with TG accumulation in the Pnpla3(148M/M) mice being caused by impaired TG mobilization from LDs...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28512563/acquired-von-willebrand-syndrome-associated-to-secondary-igm-mgus-emerging-after-autologous-stem-cell-transplantation-for-al-amyloidosis
#7
Hina Qamar, Adrienne Lee, Karen Valentine, Leslie Skeith, Victor H Jimenez-Zepeda
Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28509582/tariquidar-sensitizes-multiple-myeloma-cells-to-proteasome-inhibitors-via-reduction-of-hypoxia-induced-p-gp-mediated-drug-resistance
#8
Barbara Muz, Hubert D Kusdono, Feda Azab, Pilar de la Puente, Cinzia Federico, Mark Fiala, Ravi Vij, Noha N Salama, Abdel Kareem Azab
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28508984/successful-treatment-of-myeloma-cast-nephropathy-using-bortezomib-based-chemotherapy-plus-selective-plasma-exchange
#9
Mayuko Kawabe, Izumi Yamamoto, Ai Katsuma, Naomi Hayashi, Yo Komatsuzaki, Yasuyuki Nakada, Akihiro Shimizu, Yudo Tanno, Ichiro Ohkido, Nobuo Tsuboi, Kazuhito Suzuki, Takaki Shimada, Yoji Ogasawara, Katsuki Sugiyama, Keisuke Aiba, Takashi Yokoo
Myeloma cast nephropathy is a major complication of multiple myeloma. Recent evidence has demonstrated that the earlier induction of bortezomib-based chemotherapy with plasma exchange (PE) provides better results for kidney function and patient survival. Due to its non-selectivity, PE with albumin replacement carries the risk of fibrinogen loss, leading to bleeding. We herein report a case of successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20-year history of type II diabetes mellitus was admitted to our hospital for the evaluation of hypercalcemia, severe kidney dysfunction, and anemia...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28504846/adverse-event-management-in-patients-with-relapsed-and-refractory-multiple-myeloma-taking-pomalidomide-plus-low-dose-dexamethasone-a-pooled-analysis
#10
Philippe Moreau, Meletios A Dimopoulos, Paul G Richardson, David S Siegel, Michele Cavo, Paolo Corradini, Katja Weisel, Michel Delforge, Peter O'Gorman, Kevin Song, Christine Chen, Nizar Bahlis, Albert Oriol, Markus Hansson, Martin Kaiser, Pekka Anttila, Reinier Raymakers, Cristina Joao, Gordon Cook, Lars Sternas, Tsvetan Biyukov, Ana Slaughter, Kevin Hong, Jennifer Herring, Xin Yu, Mohamed Zaki, Jesus San-Miguel
OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs is important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. METHODS: This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy...
May 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28500235/beta-catenin-inhibitor-bc2059-is-efficacious-as-monotherapy-or-in-combination-with-proteasome-inhibitor-bortezomib-in-multiple-myeloma
#11
Ioanna Savvidou, Tiffany Khong, Andrew Cuddihy, Catriona McLean, Stephen Horrigan, Andrew Spencer
Currently available treatment options are unlikely to be curative for the majority of multiple myeloma (MM) patients, emphasizing a continuing role for the introduction of investigational agents that can overcome drug resistance. The canonical Wnt/beta-catenin signalling pathway, essential for self-renewal, growth and survival, has been found to be dysregulated in MM, particularly in advanced stages of disease. This provides the rationale for evaluating the novel beta-catenin inhibitor BC2059 as monotherapy and in combination with proteasome inhibitors in vitro and in vivo...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28497200/effect-of-lipoic-acid-on-the-biochemical-mechanisms-of-resistance-to-bortezomib-in-sh-sy5y-neuroblastoma-cells
#12
Daniele Tibullo, Cesarina Giallongo, Fabrizio Puglisi, Daniele Tomassoni, Giuseppina Camiolo, Martina Cristaldi, Maria Violetta Brundo, Carmelina Daniela Anfuso, Gabriella Lupo, Tomaso Stampone, Giovanni Li Volti, Francesco Amenta, Roberto Avola, Vincenzo Bramanti
Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in infancy. Despite the standard treatment for NB is based on the combination of chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and cisplatin, chemoresistance occurs over the time. The aim of the present research was to evaluate the effect of bortezomib (BTZ) (50 nM) on NB cell viability and how lipoic acid (ALA) (100 μM) modifies pharmacological response to this chemotherapeutic agent. Cell viability was assessed by ATP luminescence assay whereas expression of oxidative stress marker (i...
May 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28496439/bortezomib-warhead-switch-confers-dual-activity-against-mycobacterial-caseinolytic-protease-and-proteasome-and-selectivity-against-human-proteasome
#13
Wilfried Moreira, Sridhar Santhanakrishnan, Brian W Dymock, Thomas Dick
Mycobacteria harbor two main degradative proteolytic machineries, the caseinolytic protease ClpP1P2 and a proteasome. We recently showed that Bortezomib inhibits ClpP1P2 and exhibits whole cell activity against Mycobacterium tuberculosis. Bortezomib, a dipeptide with a boronic acid warhead, is a human proteasome inhibitor approved for cancer therapy. The boronic acid warhead of the compound has been shown to drive potency against both the human proteasome and ClpP1P2 protease. Selectivity for the bacterial ClpP1P2 protease over the human proteasome is lacking but needs to be achieved to move this new anti-tuberculosis lead forward...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28492559/mk2206-enhances-the-cytocidal-effects-of-bufalin-in-multiple-myeloma-by-inhibiting-the-akt-mtor-pathway
#14
Ru-Fang Xiang, Yan Wang, Nan Zhang, Wen-Bin Xu, Yang Cao, Jia Tong, Jun-Min Li, Ying-Li Wu, Hua Yan
Despite the development of promising cancer therapeutic drugs, multiple myeloma (MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of the traditional Chinese medicine Chan Su that was previously shown to exert growth suppression effects on myeloma cell lines. Previous studies conducted by our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma cells, which is considered an essential pathway to disease progression and is related to drug resistance in MM. In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226)...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#15
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28488385/the-c-797-g-a-p-r266k-cystathionine-%C3%AE-synthase-mutation-causes-homocystinuria-by-affecting-protein-stability
#16
Sapna Gupta, Liqun Wang, Warren D Kruger
Mutations in the cystathionine beta-synthase (CBS) gene are the cause of classical homocystinuria, the most common inborn error in sulfur metabolism. The c.797 G>A (p.R266K) mutation in CBS was originally described in several Norwegian pyridoxine responsive CBS deficient patients, and heterologous gene expression studies have shown that the protein has near wild-type levels of enzyme activity. Here, we characterize a transgenic mouse lacking endogenous Cbs and expressing p.R266K human CBS protein from a zinc inducible metallothionein promoter (Tg-R266K Cbs-/-)...
May 10, 2017: Human Mutation
https://www.readbyqxmd.com/read/28487980/combination-of-bortezomib-and-daunorubicin-in-the-induction-of-apoptosis-in-t-cell-acute-lymphoblastic-leukemia
#17
Xin Du, Jia Tong, Hongying Lu, Cong He, Shenghong Du, Peimin Jia, Weili Zhao, Hanzhang Xu, Junmin Li, Zhixiang Shen, Yingli Wu, Jianhua Tong, Li Zhou
Despite advances in the treatment of T‑cell acute lymphoblastic leukemia (T‑ALL), the outcome of T‑ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt‑4 T‑ALL cells and primary T‑ALL cells. Compared with treatment alone, co‑exposure of cells to bortezomib and daunorubicin resulted in a significant increase in cell death in the Jurkat cells, as evidenced by the increased percentage of Annexin V‑positive cells, the formation of apoptotic bodies...
May 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487944/bortezomib-protects-against-dextran-sulfate-sodium%C3%A2-induced-ulcerative-colitis-in-mice
#18
Li-Hong Hu, Yu-Jing Fan, Qing Li, Jing-Ming Guan, Bo Qu, Feng-Hua Pei, Bing-Rong Liu
Bortezomib, a first‑in‑class proteasome inhibitor, is a standard method of treatment in multiple myeloma. In the present study, the therapeutic effect of bortezomib was evaluated in an ulcerative colitis model induced by dextran sulfate sodium (DSS) in mice, and the mechanism of action was also investigated. Mice were administered with 3% DSS drinking water for 7 consecutive days and then they were intraperitoneally treated with bortezomib (0.2, 0.6 or 1 mg/kg) for 1, 3 or 7 days. Mice in the control group and the DSS group were provided the same volume of PBS, respectively...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28480764/novel-agents-in-mantle-cell-lymphoma
#19
David Tucker, Simon Rule
Mantle cell lymphoma (MCL) usually takes an aggressive clinical course and carries a poor prognosis. Recently, progress has been made in the treatment of MCL including the development of a number of novel agents which target intracellular pathways and the extracellular microenvironment. These agents have transformed the landscape of available therapeutic options. Areas covered: The current literature on the novel agents which currently hold a licence for the treatment of MCL in the context of front-line therapy and in the relapsed/refractory setting is summarized...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28479592/a-novel-agent-sl-401-induces-anti-myeloma-activity-by-targeting-plasmacytoid-dendritic-cells-osteoclastogenesis-and-cancer-stem-like-cells
#20
A Ray, D S Das, Y Song, V Macri, P Richardson, C L Brooks, D Chauhan, K C Anderson
Novel therapies for multiple myeloma (MM) can target mechanism(s) in the host-MM bone marrow (BM) microenvironment mediating MM progression and chemoresistance. Our studies showed increased numbers of tumor-promoting, immunosuppressive, and drug-resistant plasmacytoid dendritic cells (pDCs) in the MM BM microenvironment. pDC-MM cell interactions upregulate interleukin-3 (IL-3), which stimulates both pDC survival and MM cell growth. Since IL-3R is highly expressed on pDCs in the MM BM milieu, we here targeted pDCs using a novel IL-3R-targeted therapeutic SL-401...
May 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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