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https://www.readbyqxmd.com/read/29244631/initial-results-of-peripheral-blood-stem-cell-mobilization-collection-cryopreservation-and-engraftment-after-autologous-transplantation-confirm-that-the-capacity-building-approach-offers-good-chances-of-success-in-critical-contexts-a-kurdish-italian-cooperative
#1
Ignazio Majolino, Dereen Mohammed, Dastan Hassan, Francesco Ipsevich, Chra Abdullah, Rebar Mohammed, Angelo Palmas, Marco Possenti, Diana Noori, Dlir Ali, Harem Karem, Salah Salih, Michele Vacca, Claudia Del Fante, Angelo Ostuni, Andrea Frigato, Maria Speranza Massei, Annunziata Manna, Stefania Vasta, Marcela Gabriel, Marta Verna, Attilio Rovelli, Valentino Conter, Kosar Ali, Dosti Othman
Introduction At Hiwa Cancer Hospital (Sulaymaniyah, Iraqi Kurdistan) after the center was started by a cooperative project in June 2016, autologous transplantation was developed. Patients and Methods To develop the project, the capacity-building approach was adopted, with on-site training and coaching of personnel, educational meetings, lectures, on-the-job training, and the implementation of quality management planning. Results Here, we report initial results of peripheral-blood stem-cell mobilization and collection of the first 27 patients (age 12 to 61 years; 19 males and 8 females; multiple myeloma, n = 10; plasma cell leukemia, n = 1; Hodgkin lymphoma, n = 12; non-Hodgkin lymphoma, n = 3; and acute myeloid leukemia, n = 1)...
December 15, 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/29202016/inhibition-of-ngly1-inactivates-the-transcription-factor-nrf1-and-potentiates-proteasome-inhibitor-cytotoxicity
#2
Frederick M Tomlin, Ulla I M Gerling-Driessen, Yi-Chang Liu, Ryan A Flynn, Janakiram R Vangala, Christian S Lentz, Sandra Clauder-Muenster, Petra Jakob, William F Mueller, Diana Ordoñez-Rueda, Malte Paulsen, Naoko Matsui, Deirdre Foley, Agnes Rafalko, Tadashi Suzuki, Matthew Bogyo, Lars M Steinmetz, Senthil K Radhakrishnan, Carolyn R Bertozzi
Proteasome inhibitors are used to treat blood cancers such as multiple myeloma (MM) and mantle cell lymphoma. The efficacy of these drugs is frequently undermined by acquired resistance. One mechanism of proteasome inhibitor resistance may involve the transcription factor Nuclear Factor, Erythroid 2 Like 1 (NFE2L1, also referred to as Nrf1), which responds to proteasome insufficiency or pharmacological inhibition by upregulating proteasome subunit gene expression. This "bounce-back" response is achieved through a unique mechanism...
November 22, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29198780/pemphigus-and-hematologic-malignancies-a-population-based-study-of-11-859-patients
#3
Khalaf Kridin, Shira Zelber-Sagi, Doron Comaneshter, Erez Batat, Arnon D Cohen
BACKGROUND: The association of non-paraneoplastic pemphigus with comorbid hematologic malignancies is yet to be established. OBJECTIVE: To estimate the association between pemphigus and the common types of hematologic malignancies. METHODS: A cross-sectional study was conducted comparing pemphigus patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of 6 comorbid hematologic malignancies. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4...
November 30, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29195048/bendamustine-pamam-conjugates-for-the-improved-apoptosis-efficacy-and-in-vivo-pharmacokinetics-a-sustainable-delivery-tactic
#4
Avinash Gothwal, Iliyas Khan, Pramod Kumar, Kaisar Raza, Ankur Kaul, Anil Kumar Mishra, Umesh Gupta
Successful delivery of chemotherapeutic agent like bendamustine still remains a challenge in the clinical conditions like Chronic lymphatic leukemia (CLL), Non-Hodgkin lymphoma (NHL) and multiple myeloma. We have conjugated bendamustine to Polyamidoamine (PAMAM) dendrimers after conjugating with N-hydroxyethylmaleimide (spacer) via an ester bond. The particle size of PAMAM-bendamustine conjugate was 49.8±2.5 nm. In vitro drug release resulted in sustained release with improved solution stability of drug up to 72 h...
December 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29191842/targeting-the-anion-exchanger-2-with-specific-peptides-as-a-new-therapeutic-approach-in-b-lymphoid-neoplasms
#5
Jon Celay, Teresa Lozano, Axel R Concepcion, Elena Beltrán, Francesc Rudilla, María José García-Barchino, Eloy F Robles, Obdulia Rabal, Irene de Miguel, Carlos Panizo, Noelia Casares, Julen Oyarzabal, Jesús Prieto, Juan F Medina, Juan José Lasarte, José Ángel Martínez-Climent
Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition of their function appears as a promising immunotherapeuticimmunotherapy therapeutic approach in cancer patients. Mice with targeted deletion of the gene encoding the Cl-HCO3-anion exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in intracellular pH regulation, showed a progressive decrease in the number of Treg cells. We therefore challenged AE2 as a potential target for tumor immune therapy, and generated linear peptides designed to bind the third extracellular loop of AE2, which is crucial for its exchange activity...
November 30, 2017: Haematologica
https://www.readbyqxmd.com/read/29179521/silibinin-an-old-drug-for-hematological-disorders
#6
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Introduction: Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29178667/comprehensive-review-of-post-organ-transplant-hematologic-cancers
#7
Vikas R Dharnidharka
A higher risk for a variety of cancers is among the major complications of post-transplant immunosuppression. In this part of a continuing series on cancers post-transplant, this review focuses on the hematologic cancers after solid organ transplant. Post-transplant lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms...
November 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29165008/building-upon-the-success-of-cart19-chimeric-antigen-receptor-t-cells-for-hematologic-malignancies
#8
Antonia Rotolo, Anastasios Karadimitris, Marco Ruella
Chimeric antigen receptor T cell (CART) therapy has dramatically changed the therapeutic prospects for B cell malignancies. Over the last decade CD19-redirected CART have demonstrated the ability to induce deep, long-lasting remissions and possibly cure patients with relapsing B cell neoplasms. Such impressive results with CART19 fostered efforts to expand this technology to other incurable malignancies that naturally do not express CD19, such as acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and multiple myeloma (MM)...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#9
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29141942/frailty-and-the-management-of-hematologic-malignancies
#10
Gregory A Abel, Heidi D Klepin
The majority of blood cancers occur in the elderly. This fact conspires with an aging population in many countries to make rigorous assessment for frailty increasingly important for hematologic oncologists. In this review, we first define frailty and its relevance for patients with hematologic malignancy. Next, we review current data regarding the impact of domains of frailty on outcomes for blood cancers including myelodysplastic syndromes (MDS), acute leukemia, non-Hodgkin lymphomas such as chronic lymphocytic leukemia (CLL), and multiple myeloma...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29134229/decursin-and-decursinol-angelate-molecular-mechanism-and-therapeutic-potential-in-inflammatory-diseases
#11
REVIEW
Adeeb Shehzad, Sajida Parveen, Munibah Qureshi, Fazli Subhan, Young Sup Lee
Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C...
November 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#12
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#13
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118005/redirecting-t-cells-to-hematological-malignancies-with-bispecific-antibodies
#14
Mireya Paulina Velasquez, Challice L Bonifant, Stephen Gottschalk
There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need since it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an 'off-the-shelf' product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager (BiTE) blinatumomab has emerged as the most successful BsAb to date...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29076054/prevalence-of-use-and-cost-of-biological-drugs-for-cancer-treatment-a-5-year-picture-from-southern-italy
#15
Simona Lucchesi, Ilaria Marcianò, Paolo Panagia, Rosanna Intelisano, Maria Pia Randazzo, Carmela Sgroi, Giuseppe Altavilla, Mariacarmela Santarpia, Vincenzo Adamo, Tindara Franchina, Francesco Ferraù, Paolina Reitano, Gianluca Trifirò
BACKGROUND AND OBJECTIVES: Considering the clinical and economic burden of biological drugs in cancer treatment, it is necessary to explore how these drugs are used in routine care in Italy and how they affect the sustainability of the National Health Services. This study aimed to investigate the prevalence of use and costs of biological drugs for cancer treatment in a general population of Southern Italy in the years 2010-2014. METHODS: This was a retrospective, observational study using data from the healthcare administrative databases of Messina Province for the years 2010-2014...
October 26, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29066491/igm-myeloma-with-plasma-cell-leukemia-case-report-and-literature-review
#16
Saurabh Chhabra, Sandeep Jain, Amanda Fowler, Valeriy Sedov, Amarendra K Neppalli, Cynthia A Schandl, John Lazarchick
IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia (PCL) is a rare and aggressive variant of MM characterized by the presence of circulating plasma cells. We present a case report of a patient who presented with IgM MM in primary PCL phase with high-risk cytogenetics...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29034060/activation-of-the-aryl-hydrocarbon-receptor-and-risk-of-lymphoma-subtypes
#17
Sonia Sanna, Giannina Satta, Marina Padoan, Sara Piro, Angela Gambelunghe, Lucia Miligi, Giovanni Maria Ferri, Corrado Magnani, Giacomo Muzi, Luigi Rigacci, Maria Giuseppina Cabras, Emanuele Angelucci, Gian Carlo Latte, Attilio Gabbas, Maria Grazia Ennas, Pierluigi Cocco
The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay(®) and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE)...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/28988742/chimeric-antigen-receptor-t-cell-therapy-for-hematological-malignancies-and-solid-tumors-clinical-data-to-date-current-limitations-and-perspectives
#18
REVIEW
J Gauthier, I Yakoub-Agha
Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti-tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy...
September 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28978850/recent-topics-in-imids-and-cereblon
#19
Takumi Ito, Hiroshi Handa
Immunomodulatory drugs (IMiDs) are a new class of anticancer compounds that are derived from thalidomide. Lenalidomide and pomalidomide are well-known IMiDs, and they have already been approved by FDA for the treatment of several diseases, including multiple myeloma. Cereblon (CRBN) is a common primary target for IMiDs. It works as a substrate receptor of CRL4. Accumulating evidence has shown that the substrate specificity of CRL4(CRBN) is altered by ligands such as IMiDs. Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators"...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978241/treating-hematological-malignancies-with-cell-therapy-where-are-we-now
#20
Elisa Landoni, Barbara Savoldo
Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative 'live-drug'. Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells...
October 5, 2017: Expert Opinion on Biological Therapy
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