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Leukemia, multiple myeloma

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https://www.readbyqxmd.com/read/29453626/drug-approval-based-on-randomized-phase-3-trials-for-relapsed-malignancy-analysis-of-oncologic-drugs-granted-accelerated-approval-publications-and-clinical-trial-databases
#1
Sumimasa Nagai, Keiya Ozawa
Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29450644/pi3k-akt-inhibitor-ly294002-potentiates-homoharringtonine-antimyeloma-activity-in-myeloma-cells-adhered-to-stromal-cells-and-in-scid-mouse-xenograft
#2
Ping Chen, Xiaofang Wen, Bin Wang, Diyu Hou, Hong Zou, Qin Yuan, Hui Yang, Jieqiong Xie, Huifang Huang
Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche...
February 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#3
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with 89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29432497/autologous-t-cells-expressing-the-oncogenic-transcription-factor-klf6-sv1-prevent-apoptosis-of-chronic-lymphocytic-leukemia-cells
#4
Parviz Kokhaei, Mohammad Hojjat-Farsangi, Fariba Mozaffari, Ali Moshfegh, Fatemeh Pak, Ali Rashidy-Pour, Marzia Palma, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10)...
2018: PloS One
https://www.readbyqxmd.com/read/29427192/community-acquired-respiratory-infections-are-common-in-patients-with-non-hodgkin-lymphoma-and-multiple-myeloma
#5
Noa Lavi, Irit Avivi, Zipora Kra-Oz, Ilana Oren, Emilia Hardak
PURPOSE: Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis...
February 9, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29416917/camp-induces-cell-apoptosis-in-multiple-myeloma-and-overcomes-bortezomib-resistance
#6
Yingying Wang, Yong Tang, Haifang Hang, Mingming Wang, Yuyang Pang, Yehua Yu, Yingli Wu, Qi Zhu
The acquired resistance to bortezomib represents a major obstacle for multiple myeloma (MM) treatment. Studies revealed that the treatment with cyclic adenosine monophosphate (cAMP) may be a promising strategy for MM therapy. Therefore, the present study aimed to explore the mechanism of action of cAMP in MM cells. Our results showed that 8-CPT-cAMP and bortezomib synergistically induced growth inhibition and apoptosis in MM bortezomib-resistant cell lines and primary MM cells, in which protein kinase A (PKA) activation was involved...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29390389/treatment-related-acute-granulocyte-monocytic-leukemia-from-multiple-myeloma-a-case-report-and-literature-review
#7
REVIEW
Juan Qian, Wenyu Shi, Li Yang, Zenghua Lin, Yifeng Cai, Hong Liu
RATIONALE: To investigate the clinical features of treatment-related acute granulocyte-monocytic leukemia (t-AML) from multiple myeloma (MM) thereby improving the understanding of this disease. PATIENT CONCERNS: A 72-year-old woman patient was initially diagnosed as MM. Two years and 7 months after treatment, this patient developed AML M4 as confirmed by the analyses from clinical features, bone marrow morphology, flow cytometry, and cytogenetic examination. DIAGNOSIS: Treatment-related acute myeloid leukaemia (t-AML)...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29389522/wnt-signaling-in-hematological-malignancies
#8
Stephanie Grainger, David Traver, Karl Willert
Leukemia and lymphoma are a wide encompassing term for a diverse set of blood malignancies that affect people of all ages and result in approximately 23,000 deaths in the United States per year (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.). Hematopoietic stem cells (HSCs) are tissue-specific stem cells at the apex of the hierarchy that gives rise to all of the terminally differentiated blood cells, through progressively restricted progenitor populations, a process that is known to be Wnt-responsive...
January 2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29377227/lymphoproliferative-disorders-in-patients-with-chronic-myeloproliferative-neoplasms-a-systematic-review
#9
Monia Marchetti, Alessandra Carobbio, Enrica Capitoni, Tiziano Barbui
Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. In order to systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%) or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous...
January 27, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29375856/acute-lymphoblastic-leukemia-secondary-to-myeloproliferative-neoplasms-or-after-lenalidomide-exposure
#10
Ahmad Alhuraiji, Kiran Naqvi, Yang O Huh, Coty Ho, Srdan Verstovsek, Prithviraj Bose
Philadelphia-negative (Ph-) myeloproliferative neoplasms (MPN) do rarely transform to acute lymphoblastic leukemia (ALL). While causality is difficult to establish, a few cases of ALL arising after exposure to lenalidomide for registered indications (multiple myeloma, myelodysplastic syndrome with 5q deletion) have been described in the literature.
January 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29360725/clinical-development-of-pd-1-blockade-in-hematologic-malignancies
#11
Matthew J Pianko, Aaron D Goldberg, Alexander M Lesokhin
Clinical development of immune checkpoint inhibitors targeting the PD-1 pathway has led to clinical benefits for patients with multiple solid tumor and hematologic malignancies and has revolutionized modern oncology. High response rates to PD-1 blockade in patients with classical Hodgkin lymphoma and certain subtypes of non-Hodgkin lymphoma highlight an intrinsic biologic sensitivity to this strategy of treatment. Despite early success of checkpoint inhibitor and immunomodulatory drug combinations in phase 2 studies in multiple myeloma, safety concerns in patients treated with the combination of immunomodulatory drugs and checkpoint inhibitors in myeloma have stalled drug development in this space...
January 2018: Cancer Journal
https://www.readbyqxmd.com/read/29346543/the-impact-of-reported-beta-lactam-allergy-in-hospitalized-patients-with-hematologic-malignancies-requiring-antibiotics
#12
Kuan-Hsiang Gary Huang, Valerie Cluzet, Keith Hamilton, Olajumoke Fadugba
Background: Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown. Objective: To define the impact of reported BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients requiring systemic antibiotics. Methods: Retrospective cohort study of adult inpatients with hematologic malignancy admitted at two tertiary care hospitals 2010-2015...
January 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29323398/night-shift-work-and-hematological-cancers-a-population-based-case-control-study-in-three-nordic-countries
#13
Madar Talibov, Eero Pukkala, Jan Ivar Martinsen, Laufey Tryggvadottir, Elisabete Weiderpass, Johnni Hansen
Objective The aim of this case-control study was to assess the effect of night-shift work on the risk of hematological cancers. Methods The study included 39 371 leukemia, 56 713 non-Hodgkin lymphoma, 9322 Hodgkin lymphoma, and 26 188 multiple myeloma cases diagnosed between 1961 and 2005 in Finland, Sweden, and Iceland. Five controls for each case were selected from the Nordic Occupational Cancer Study (NOCCA) cohort, matched by year of birth, sex and country. Night-shift exposure was assessed by using the NOCCA job-exposure matrix (JEM)...
January 11, 2018: Scandinavian Journal of Work, Environment & Health
https://www.readbyqxmd.com/read/29312638/coregulator-profiling-of-the-glucocorticoid-receptor-in-lymphoid-malignancies
#14
Dorien Clarisse, Jonathan Thommis, Karlien Van Wesemael, René Houtman, Dariusz Ratman, Jan Tavernier, Fritz Offner, Ilse Beck, Karolien De Bosscher
Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#15
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29300814/body-mass-index-and-20-specific-cancers-re-analyses-of-dose-response-meta-analyses-of-observational-studies
#16
E K Choi, H B Park, K H Lee, J H Park, M Eisenhut, H J van der Vliet, G Kim, J I Shin
Background: Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between Body Mass Index (BMI) and risk of developing cancer. Methods: We performed an umbrella review and comprehensively re-analysed the data of dose-response meta-analyses on associations between BMI and risk of 20-specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, oesophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies...
December 28, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29296780/interleukin-6-levels-predict-event-free-survival-in-pediatric-aml-and-suggest-a-mechanism-of-chemotherapy-resistance
#17
Alexandra M Stevens, Jennifer M Miller, Jaime O Munoz, Amos S Gaikwad, Michele S Redell
The tumor microenvironment can protect cancer cells from conventional anticancer therapies. Thus, targeting these protective mechanisms could eradicate therapy-resistant cancer cells and improve outcomes. Interleukin-6 (IL-6) provides extrinsic protection for several solid tumors and multiple myeloma. In pediatric acute myeloid leukemia (AML), IL-6-induced STAT3 signaling frequently becomes stronger at relapse, and increases in IL-6-induced STAT3 activity are associated with inferior survival after relapse...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296751/a-novel-cxcr4-antagonist-igg1-antibody-pf-06747143-for-the-treatment-of-hematologic-malignancies
#18
Shu-Hui Liu, Yin Gu, Bernadette Pascual, Zhengming Yan, Max Hallin, Cathy Zhang, Conglin Fan, Wenlian Wang, Justine Lam, Mary E Spilker, Rolla Yafawi, Eileen Blasi, Brett Simmons, Nanni Huser, Wei-Hsien Ho, Kevin Lindquist, Thomas-Toan Tran, Jyothirmayee Kudaravalli, Jing-Tyan Ma, Gretchen Jimenez, Ishita Barman, Colleen Brown, Sherman Michael Chin, Maria J Costa, David Shelton, Tod Smeal, Valeria R Fantin, Flavia Pernasetti
The chemokine receptor CXCR4 is highly expressed and associated with poor prognosis in multiple malignancies. Upon engagement by its ligand, CXCL12, CXCR4 triggers intracellular signaling pathways that control trafficking of cells to tissues where the ligand is expressed, such as the bone marrow (BM). In hematologic cancers, CXCR4-driven homing of malignant cells to the BM protective niche is a key mechanism driving disease and therapy resistance. We developed a humanized CXCR4 immunoglobulin G1 (IgG1) antibody (Ab), PF-06747143, which binds to CXCR4 and inhibits CXCL12-mediated signaling pathways, as well as cell migration...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286493/twenty-five-years-of-the-national-academy-of-medical-sciences-of-ukraine-progress-and-priorities-for-future-of-radiation-medicine-and-biology
#19
D Bazyka
After the creation of the Academy of Medical Sciences of Ukraine in 1993 the Research Center for Radiation Medicine was among the first institutions to join the Academy (fig. 1). Estab lishing the Academy was among the first steps of the independent Ukrainian government and aimed to provide a high level health care for population. It was extremely needed for the minimization of Chornobyl medical consequences. This choice was related to a growing recognition of the scientific research in fulfilling the Сenter's mission - study of the effects of low dose radiation on human body and radiation protection of the exposed population...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29251284/prevention-and-management-of-adverse-events-of-novel-agents-in-multiple-myeloma-a-consensus-of-the-european-myeloma-network
#20
REVIEW
H Ludwig, M Delforge, T Facon, H Einsele, F Gay, P Moreau, H Avet-Loiseau, M Boccadoro, R Hajek, M Mohty, M Cavo, M A Dimopoulos, J F San-Miguel, E Terpos, S Zweegman, L Garderet, M-V Mateos, G Cook, X Leleu, H Goldschmidt, G Jackson, M Kaiser, K Weisel, N W C J van de Donk, A Waage, M Beksac, U H Mellqvist, M Engelhardt, J Caers, C Driessen, P Sonneveld
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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