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Berdien E Oortgiesen, Roshna Azad, Marc H Hemmelder, Robby E Kibbelaar, Nic J G M Veeger, Joost C de Vries, Eric N van Roon, Mels Hoogendoorn
No abstract text is available yet for this article.
March 15, 2018: Haematologica
Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Kenichi Aihara, Mariko Ikuo, Kohji Itoh, Koichiro Hayashi, Michihiro Nakamura, Masahiro Abe
Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death...
February 13, 2018: Oncotarget
Khawar Abbas, Muhammed Mubarak, Mirza Naqi Zafar, Wajiha Musharraf, Mehjabeen Imam, Tahir Aziz, Adibul Hassan Rizvi
OBJECTIVES: Plasma cell-rich acute rejection is an aggressive form of acute rejection that occurs late after transplant and is usually resistant to standard antirejection therapy. This study reports the safety, efficacy, and outcomes of plasma cell-rich acute rejection after treatment with bortezomib, a proteasome inhibitor, in 10 patients after a first living-related renal transplant. MATERIALS AND METHODS: Plasma cell-rich acute rejection was diagnosed using the 2007 Banff classification...
March 9, 2018: Experimental and Clinical Transplantation
Tia H Turner, Mohammad A Alzubi, Sahib S Sohal, Amy L Olex, Mikhail G Dozmorov, J Chuck Harrell
PURPOSE: Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. METHODS: We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro...
March 12, 2018: Breast Cancer Research and Treatment
Paolo Milani, Giampaolo Merlini, Giovanni Palladini
Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Kojima, Yuka Sone, Shimpei Uraguchi, Masako Kiyono
Cancer cells enhance autophagic activity as a survival measure against metabolic and therapeutic stresses. The inhibition of autophagy may represent a valuable sensitizing target for cancer treatment. Recently, we examined the ability of various cytochalasins to inhibit autophagy and demonstrated the potent inhibitory effect of cytochalasin E (CE) on autophagic flux. The present study was conducted to investigate whether CE inhibited autophagosome-lysosome fusion, and to determine whether CE enhanced chemotherapy-induced cell death...
March 7, 2018: Biochemical and Biophysical Research Communications
Chong Chyn Chua, Hui Yin Lim, Khai Li Chai, Jeremy Ong, Shirlene Sim, Colin Wood, Michael Dickinson, Philip Campbell, Jennifer Hempton, Hayley King, Claire Dowsing, Krystal Bergin, Sharon Muir, Simon Gibbs, Andrew Grigg
Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m2 ; high dose: 3-4 g/m2 ) PBSC mobilisation strategies in 288 patients who only received bortezomib, cyclophosphamide and dexamethasone (VCD) induction prior to autograft across six apheresis centres from November 2012 to June 2017...
March 9, 2018: Bone Marrow Transplantation
Manu Jain, Grs Budinger, Borko Jovanovic, Jane Dematte, Sara Duffey, Jayesh Mehta
Pulmonary chronic graft-versus-host disease (p-CGVHD) following allogeneic HSCT is devastating with limited proven treatments. Although sporadically associated with pulmonary toxicity, the proteasome inhibitor bortezomib may be efficacious in p-CGVHD. We sought to establish safety and tolerability of bortezomib in pilot, open-label trial of patients with p-CGVHD. The primary endpoint was adverse events. Efficacy was assessed by comparing FEV1 decline prior to p-CGVHD diagnosis to during the bortezomib treatment period...
March 9, 2018: Bone Marrow Transplantation
Karine Augeul-Meunier, Marie-Lorraine Chretien, Anne-Marie Stoppa, Lionel Karlin, Lofti Benboubker, Jose Miguel Torregrosa Diaz, Mohamad Mohty, Ibrahim Yakoub-Agha, Jacques-Olivier Bay, Aurore Perrot, Claude-Eric Bulabois, Anne Huynh, Mélanie Mercier, Laurent Frenzel, Hervé Avet-Loiseau, Régis Peffault de Latour, Jérôme Cornillon
Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy...
March 9, 2018: Bone Marrow Transplantation
Eirini Katodritou, Evangelos Terpos, Sossana Delimpasi, Maria Kotsopoulou, Eurydiki Michalis, Chrysanthi Vadikolia, Marie-Christine Kyrtsonis, Argiris Symeonidis, Nikolaos Giannakoulas, Chrissa Vadikolia, Michalis Michael, Christina Kalpadakis, Theodora Gougopoulou, Chrystalla Prokopiou, Georgia Kaiafa, Dimitrios Christoulas, Maria Gavriatopoulou, Evlampia Giannopoulou, Vasiliki Labropoulou, Evgenia Verrou, Efstathios Kastritis, Pavlina Konstantinidou, Achilles Anagnostopoulos, Meletios A Dimopoulos
We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%...
March 9, 2018: Blood Cancer Journal
Madeliene Parrott, Simon Rule
Mantle cell lymphoma (MCL) is a rare but often aggressive B-cell non-Hodgkin lymphoma (NHL). Initial therapy can achieve high response rates but invariably patients relapse and die from their disease. Incorporating a maintenance phase into the treatment strategy may prolong remission duration and ultimately prolong survival. Areas covered: The current literature incorporating a maintenance phase into treatment strategies for newly diagnosed and pre-treated MCL patients has been summarized. A literature search was performed using search terms "mantle cell lymphoma", "indolent NHL", "maintenance", "interferon", "rituximab", "lenalidomide", "bortezomib" and "ibrutinib"...
March 9, 2018: Expert Review of Hematology
Young Shin Lee, Woong Heo, Jiho Nam, Young Hwa Jeung, Jaeho Bae
Bortezomib, which is a potent proteasome inhibitor, has been used as a first-line drugs to treat multiple myeloma for a few decades, and radiotherapy has frequently been applied to manage acute bone lesions in the patients. Therefore, it was necessary to investigate what the benefits might be if the two therapies were applied simultaneously in the treatment of multiple myeloma. Since it was known that radiotherapy and proteasome inhibitors could increase the expression of NKG2D ligands through induction of protein synthesis and suppression of protein degradation of NKG2D ligands, respectively, we supposed that the combined treatment might further enhance the expression of NKG2D ligands...
March 6, 2018: Journal of Radiation Research
Takashi Yoshida, Masaki Ri, Takashi Kanamori, Sho Aoki, Reham Ashour, Shiori Kinoshita, Tomoko Narita, Haruhito Totani, Ayako Masaki, Asahi Ito, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Shun Kitahata, Takuya Chiba, Satoshi Ichikawa, Shinsuke Iida
Proteasome inhibitors (PI), mainly targeting the β5 subunit of the 20S proteasome, are widely used in the treatment of multiple myeloma (MM). However, PI resistance remains an unresolved problem in the therapy of relapsed and refractory MM. To develop a new PI that targets other proteasome subunits, we examined the anti-MM activity of a novel syringolin analog, syringolog-1, which inhibits the activity of both the β5 and β2 subunits. Syringolog-1 exhibited marked cytotoxicity against various MM cell lines and anti-tumor activity towards bortezomib (Btz)-resistant MM cells through the dual inhibition of chymotrypsin-like (β5 subunit) and trypsin-like (β2 subunit) activities...
February 9, 2018: Oncotarget
Moritz Horn, Virginia Kroef, Kira Allmeroth, Nicole Schuller, Stephan Miethe, Martin Peifer, Josef M Penninger, Ulrich Elling, Martin S Denzel
Forward genetic screens in haploid mammalian cells have recently emerged as powerful tools for the discovery and investigation of recessive traits. Use of the haploid system provides unique genetic tractability and resolution. Upon positive selection, these screens typically employ analysis of loss-of-function (LOF) alleles and are thus limited to non-essential genes. Many relevant compounds, including anti-cancer therapeutics, however, target essential genes, precluding positive selection of LOF alleles. Here, we asked whether the use of random and saturating chemical mutagenesis might enable screens that identify essential biological targets of toxic compounds...
February 9, 2018: Oncotarget
Ludwig Erik Aguilar, Batgerel Tumurbaatar, Amin Ghavaminejad, Chan Hee Park, Cheol Sang Kim
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 6, 2018: Scientific Reports
Dae Hyun Lee, Michael G Fradley
PURPOSE OF REVIEW: Multiple myeloma treatment regimens consist of proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), and steroids. In this paper, we will review the pathophysiology and associated cardiotoxicities of the different multiple myeloma therapeutic modalities and present methods to mitigate the development of cardiovascular complications. RECENT FINDINGS: Although proteasome inhibitors and immunomodulatory drugs have led to significant improvements in oncologic outcomes, there is increasing evidence of serious cardiovascular side effects which may be exacerbated in the setting of underlying cardiovascular risk factors or disease...
March 6, 2018: Current Treatment Options in Cardiovascular Medicine
C P Sawicki, S A Climans, C C Hsia, J A Fraser
Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid...
February 2018: Current Oncology
Yuan Qing Qu, Flora Gordillo-Martinez, Betty Yuen Kwan Law, Yu Han, Anguo Wu, Wu Zeng, Wai Kei Lam, Charles Ho, Simon Wing Fai Mok, Hu Qiang He, Vincent Kam Wai Wong, Renxiao Wang
Non-small-cell lung cancer (NSCLC) accounts for most lung cancer cases. Therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. The proteasome system has been demonstrated clinically as a potent therapeutic target for haematological cancers. However, promising preclinical data in solid tumors are yet to be confirmed in clinics. Herein, the combinational use of Bortezomib (BZM) and 2-aminoethoxydiphenylborane (2-APB) toward NSCLC cells was studied...
March 2, 2018: Cell Death & Disease
Eric M Maiese, Claire Ainsworth, Jean-Gabriel Le Moine, Outi Ahdesmäki, Judith Bell, Emma Hawe
PURPOSE: New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been compared in head-to-head clinical trials to determine the most efficacious therapy. In an update of the POLLUX (Phase 3 Study Comparing DRd Versus Rd in Subjects with Relapsed or Refractory Multiple Myeloma [RRMM]) trial, median progression-free survival (PFS) for DRd was not reached; the hazard ratio compared with Rd was 0...
February 27, 2018: Clinical Therapeutics
Kenny Kwok-Hei Yu, Jessica T Taylor, Omar N Pathmanaban, Amir Saam Youshani, Deniz Beyit, Joanna Dutko-Gwozdz, Roderick Benson, Gareth Griffiths, Ian Peers, Peter Cueppens, Brian A Telfer, Kaye J Williams, Catherine McBain, Ian D Kamaly-Asl, Brian W Bigger
BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation...
2018: PloS One
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