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Leukemia, multiple myeloma, lymphoma

Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
András Kotschy, Zoltán Szlavik, James Murray, James Davidson, Ana Leticia Maragno, Gaëtane Le Toumelin-Braizat, Maïa Chanrion, Gemma L Kelly, Jia-Nan Gong, Donia M Moujalled, Alain Bruno, Márton Csekei, Attila Paczal, Zoltán B Szabo, Szabolcs Sipos, Gábor Radics, Agnes Proszenyak, Balázs Balint, Levente Ondi, Gábor Blasko, Alan Robertson, Allan Surgenor, Pawel Dokurno, Ijen Chen, Natalia Matassova, Julia Smith, Christopher Pedder, Christopher Graham, Aurélie Studeny, Gaëlle Lysiak-Auvity, Anne-Marie Girard, Fabienne Gravé, David Segal, Chris D Riffkin, Giovanna Pomilio, Laura C A Galbraith, Brandon J Aubrey, Margs S Brennan, Marco J Herold, Catherine Chang, Ghislaine Guasconi, Nicolas Cauquil, Fabien Melchiore, Nolwen Guigal-Stephan, Brian Lockhart, Frédéric Colland, John A Hickman, Andrew W Roberts, David C S Huang, Andrew H Wei, Andreas Strasser, Guillaume Lessene, Olivier Geneste
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway...
October 19, 2016: Nature
Claire de Oliveira, Reka Pataky, Karen E Bremner, Jagadish Rangrej, Kelvin K W Chan, Winson Y Cheung, Jeffrey S Hoch, Stuart Peacock, Murray D Krahn
BACKGROUND: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada. METHODS: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092)...
October 18, 2016: BMC Cancer
Sameem M Abedin, Craig S Boddy, Hidayatullah G Munshi
The bromodomain and extra-terminal (BET) family of proteins are important epigenetic regulators involved in promoting gene expression of critical oncogenes. BET inhibitors have been demonstrated to repress c-Myc expression, and were initially shown to have efficacy in a number of c-Myc-dependent hematologic malignancies. Recent studies have now revealed a broader role for BET inhibitors in hematologic malignancies. In this review, we summarize the efficacy of BET inhibitors in preclinical models of acute leukemia, lymphoma, and multiple myeloma...
2016: OncoTargets and Therapy
Sheela V Godbole, Karabi Nandy, Mansi Gauniyal, Pallavi Nalawade, Suvarna Sane, Shravani Koyande, Joy Toyama, Asha Hegde, Phil Virgo, Kishor Bhatia, Ramesh S Paranjape, Arun R Risbud, Sam M Mbulaiteye, Ronald T Mitsuyasu
We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods...
September 2016: Medicine (Baltimore)
Irina S Kuznetsova, Elena V Labutina, Nezahat Hunter
Incidence of all types of lymphatic and hematopoietic cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, acute and chronic myeloid leukemia (AML and CML respectively), chronic lymphocytic leukemia (CLL) and other forms of leukemia have been studied in a cohort of 22,373 workers employed at the Mayak Production Association (PA) main facilities during 536,126 person-years of follow-up from the start of employment between 1948 and 1982 to the end of 2004. Risk assessment was performed for both external gamma-radiation and internal alpha-exposure of red bone marrow due to incorporated Pu-239 using Mayak Workers Dosimetry System 2008 taking into account non-radiation factors...
2016: PloS One
Daniel Walker, Ying Li, Áron Roxin, Paul Schaffer, Michael J Adam, David M Perrin
The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, (111)In-SPECT, and (64)Cu- and (68)Ga-PET imaging. Despite these successes, to date there is no report of an (18)F-labeled LLP2A conjugate. Notably, fluorine-18 is a preferred radionuclide for PET imaging, yet its short half-life and general inactivity under aqueous conditions present challenges for peptide labeling...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Lucía Martínez-Hernández, Diana Vilar-Compte, Patricia Cornejo-Juárez, Patricia Volkow-Fernández
INTRODUCTION: Nosocomial pneumonia (NP) in patients with hematological malignancies (HM) has an attributable mortality over 90%. There are few studies that report the incidence of nosocomial infections in patients with HM. OBJECTIVE: To describe the epidemiology and clinical course of NP in a cohort of patients with hematologic malignancies. MATERIAL AND METHODS: Single-center study of patients with leukemia, lymphoma or multiple myeloma diagnosed with NP, hospitalized between January 2011 and December 2012...
July 2016: Gaceta Médica de México
Mark B Geyer, Renier J Brentjens
The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL)...
November 2016: Cytotherapy
Garrett W Rhyasen, Maureen Hattersley, Yi Yao, Austin Dulak, Wenxian Wang, Philip Petteruti, Ian Dale, Scott Boiko, Tony Cheung, Jingwen Zhang, Shenghua Wen, Lillian Castriotta, Deborah Lawson, Michael Collins, Larry Bao, Miika J Ahdesmaki, Graeme Walker, Greg O'Connor, Tammie Yeh, Alfred A Rabow, Jonathan Dry, Corinne Reimer, Paul Lyne, Gordon B Mills, Stephen Fawell, Michael J Waring, Michael Zinda, Edwin Clark, Huawei Chen
The bromodomain and extraterminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated chromatin. Pharmacological targeting of BRD4 bromodomains by small-molecule inhibitors has proven to be an effective means to disrupt aberrant transcriptional programs critical for tumor growth and/or survival. Herein, we report AZD5153, a potent, selective, and orally available BET/BRD4 bromodomain inhibitor possessing a bivalent binding mode. Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously...
August 29, 2016: Molecular Cancer Therapeutics
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
Jorge J Castillo, Morie A Gertz
In recent years, the survival of patients with plasma cell dyscrasias has improved due to improvements in anticancer and supportive therapy. However, the risk of secondary malignancies has increased, thought to be due to a combination of environmental and disease-related factors, as well as treatment. In the present review, we evaluate the risk of secondary malignancies in patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Patients with MGUS appear to have a higher risk of developing myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)...
August 22, 2016: Leukemia & Lymphoma
Xiangyu Zhao, Feng Gao, Xiaohui Zhang, Yu Wang, Lanping Xu, Kaiyan Liu, Xiaosu Zhao, Yingjun Chang, Han Wei, Huan Chen, Yuhong Chen, Zhengfan Jiang, Xiaojun Huang
The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation (HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation (HPBSCT) for acute leukemia (AL) not in remission (NR) or in more than the second complete remission (>CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma (MM), or non-Hodgkin lymphoma (NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study...
August 17, 2016: Science China. Life Sciences
Gianfranco Alicandro, Matteo Rota, Paolo Boffetta, Carlo La Vecchia
Data on the risk of lymphatic and hematopoietic neoplasms among workers whose jobs entail high exposure to polycyclic aromatic hydrocarbons (PAH) are sparse, and mainly based on small-size studies. We carried out a systematic review of occupational cohort studies that reported results on incidence or mortality from Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), leukemia or multiple myeloma (MM) among workers exposed to PAH. We computed meta-analytic estimates using a random effect model. Meta-relative risk (meta-RR) was computed separately by each type of neoplasm, job or industry...
November 2016: Archives of Toxicology
Miranda M Fidler, Isabelle Soerjomataram, Freddie Bray
Socioeconomic factors are associated with cancer incidence through complex and variable pathways. We assessed cancer incidence for all cancers combined and 27 major types according to national human development levels. Using GLOBOCAN data for 184 countries, age-standardized incidence rates (ASRs) were assessed by four levels (low, medium, high, very high) of the Human Development Index (HDI), a composite index of life expectancy, education, and gross national income. A strong positive relationship between overall cancer incidence and HDI level was observed...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
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
Daniel R Couriel, Holly Ricker, Mary Steinbach, Catherine J Lee
Neurologic manifestations are common in blood diseases, and they can be caused by the hematologic disorder or its treatment. This article discusses hematologic diseases in adult patients, and categorizes them into benign and malignant conditions. The more common benign hematologic diseases associated with neurologic manifestations include anemias, particularly caused by B12 deficiency and sickle cell disease, and a variety of disorders of hemostasis causing bleeding or thrombosis, including thrombotic microangiopathy...
August 2016: Hematology/oncology Clinics of North America
Y L Zhou, X D Wei, R H Mi, H Ai, L N Zhang, Y Y Liu, Y F Li, Y P Song
OBJECTIVE: To improve the clinical understanding of fungal esophagitis in patients with hematologic malignancies. METHOD: The clinical data of a cohort of 279 patients with hematologic malignancies who underwent gastroscopy between 2012 and 2015 in the Endoscopy Center of Henan Tumor Hospital were retrospectively analyzed. To investigate the clinical characteristics and prognosis of fungal esophagitis in patients with heratologic malignancies. RESULTS: 13 of the 279 patients were diagnosed as fungal esophagitis (4...
June 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Hossam K Mahmoud, Mohamed A Samra, Gamal M Fathy
Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy...
July 2016: Journal of Advanced Research
Natsuyo Yoshida-Hata, Naomichi Katai, Toshiyuki Oshitari
Purpose. To report the ocular findings in patients with hematopoietic malignancy with optic nerve involvement and abducens nerve palsy. Methods. The medical records of all cases of hematopoietic cancer with ophthalmic involvements seen in the Department of Ophthalmology of the National Center for Global Health and Medicine between 2009 and 2014 were reviewed. Results. Eight patients with hematopoietic cancer with optic nerve invasion or abducens nerve palsy were studied. The primary diseases were 3 cases of multiple myeloma, 1 case of acute lymphocytic leukemia, 1 case of follicular lymphoma, and 3 cases of AIDS-related lymphoma...
2016: Case Reports in Ophthalmological Medicine
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