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https://www.readbyqxmd.com/read/28441374/fever-in-patients-with-cancer
#1
Yanina Pasikhova, Steven Ludlow, Aliyah Baluch
BACKGROUND: The definition of fever is flexible and depends on the clinical context. Fever is frequently observed in patients with cancer. METHODS: Infectious and noninfectious causes of fever in patients with various oncological and hematological malignancies and the usefulness of biomarkers are discussed. RESULTS: To treat patients in a timely manner and to minimize morbidity and mortality, it is paramount that health care professionals determine the cause of fever...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#2
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28423573/involvement-of-af1q-mllt11-in-the-progression-of-ovarian-cancer
#3
Paola Tiberio, Ludmila Lozneanu, Valentina Angeloni, Elena Cavadini, Patrizia Pinciroli, Maurizio Callari, Maria Luisa Carcangiu, Domenica Lorusso, Francesco Raspagliesi, Valentina Pala, Maria Grazia Daidone, Valentina Appierto
The functional role of AF1q/MLLT11, an oncogenic factor involved in a translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been investigated in hematological and solid malignancies and its expression was found to be linked to tumor progression and poor clinical outcome. In addition to its oncogenic function, AF1q has been shown to play a role in the onset of basal and drug-induced apoptosis in cancer cells of different histotypes, including ovarian cancer. Through in vitro, ex vivo, and in silico approaches, we demonstrated here that AF1q is also endowed with protumorigenic potential in ovarian cancer...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420721/phase-i-study-of-fenretinide-delivered-intravenously-in-patients-with-relapsed-or-refractory-hematologic-malignancies-a-california-cancer-consortium-trial
#4
Ann Mohrbacher, Allen S Yang, Susan Groshen, Shivaani Kummar, Martin E Gutierrez, Min H Kang, Denice Tsao-Wei, C Patrick Reynolds, Edward Newman, Barry J Maurer
A phase I study was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies. <br /><br />Experimental Design: Fenretinide (80 - 1810 mg/m(2)/day) was administered by continuous infusion on Days 1 - 5, in 21-day cycles, using an accelerated titration design. <br /><br />Results: Twenty-nine patients, treated with a median of three prior regimens (range, 1 to 7), were enrolled and received test drug...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28419480/characterization-of-neutropenia-in-advanced-cancer-patients-following-palbociclib-treatment-using-a-population-pharmacokinetic-pharmacodynamic-modeling-and-simulation-approach
#5
Wan Sun, Peter J O'Dwyer, Richard S Finn, Ana Ruiz-Garcia, Geoffrey I Shapiro, Gary K Schwartz, Angela DeMichele, Diane Wang
Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was developed to describe the time course of absolute neutrophil count (ANC) and quantify the exposure-response relationship for neutropenia. These analyses help in understanding neutropenia associated with palbociclib and its comparison with chemotherapy-induced neutropenia...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28413661/non-alcoholic-fatty-liver-disease-fibrosis-score-predicts-hematological-toxicity-of-chemotherapy-including-irinotecan-for-colorectal-cancer
#6
Masashi Yahagi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Yuko Kitagawa
Liver dysfunction that may affect drug metabolism is a major concern in patients treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is crucial for predicting the adverse events of chemotherapy. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring system constructed from routine clinical and laboratory variables. The aim of this study was to evaluate whether NFS was useful for predicting the adverse events of chemotherapy including irinotecan (CPT-11) for colorectal cancer...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28413320/panax-ginseng-meyer-prevents-radiation-induced-liver-injury-via-modulation-of-oxidative-stress-and-apoptosis
#7
Hyeong-Geug Kim, Seong-Soon Jang, Jin-Seok Lee, Hyo-Seon Kim, Chang-Gue Son
BACKGROUND: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. METHODS: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#8
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28407743/new-drugs-new-toxicities-severe-side-effects-of-modern-targeted-and-immunotherapy-of-cancer-and-their-management
#9
REVIEW
Frank Kroschinsky, Friedrich Stölzel, Simone von Bonin, Gernot Beutel, Matthias Kochanek, Michael Kiehl, Peter Schellongowski
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity...
April 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28404756/infusion-compatible-antibiotic-formulations-for-rapid-administration-to-improve-outcomes-in-cancer-outpatients-with-severe-sepsis-and-septic-shock-the-sepsis-stat-pack
#10
Jason D Goldman, Amelia Gallaher, Rupali Jain, Zach Stednick, Manoj Menon, Michael J Boeckh, Paul S Pottinger, Stephen M Schwartz, Corey Casper
Background: Patients with cancer are at high risk for severe sepsis and septic shock (SS/SSh), and a delay in receiving effective antibiotics is strongly associated with mortality. Delays are due to logistics of clinic flow and drug delivery. In an era of increasing antimicrobial resistance, combination therapy may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP) program to simplify timely and effective provision of empiric antibiotics and other resuscitative care to outpatients with cancer with suspected SS/SSh before hospitalization...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28381120/simultaneous-assessment-of-the-efficacy-and-toxicity-of-marine-mollusc-derived-brominated-indoles-in-an-in-vivo-model-for-early-stage-colon-cancer
#11
Babak Esmaeelian, Kirsten Benkendorff, Richard K Le Leu, Catherine A Abbott
The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita, while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later...
April 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28378227/epigenetic-approach-for-angiostatic-therapy-promising-combinations-for-cancer-treatment
#12
REVIEW
Robert H Berndsen, U Kulsoom Abdul, Andrea Weiss, Marloes Zoetemelk, Marije T Te Winkel, Paul J Dyson, Arjan W Griffioen, Patrycja Nowak-Sliwinska
Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs have been approved for cancer chemotherapy, mainly for hematological applications. Limitations in single-drug efficacies have thus far limited their application in the treatment of solid tumors. Nevertheless, promising activity for these compounds has been suggested when combined with other, distinctly targeted agents...
April 4, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28375741/isocitrate-dehydrogenase-mutation-and-r-2-hydroxyglutarate-from-basic-discovery-to-therapeutics-development
#13
Lenny Dang, Shin-San Michael Su
The identification of heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) in subsets of cancers, including secondary glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinoma, and chondrosarcomas, led to intense discovery efforts to delineate the mutations' involvement in carcinogenesis and to develop therapeutics, which we review here. The three IDH isoforms nicotinamide adenine dinucleotide phosphate-dependent IDH1 and IDH2, and nicotinamide adenine dinucleotide-dependent IDH3) contribute to regulating the circuitry of central metabolism...
April 3, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28346313/population-pharmacokinetics-of-gemcitabine-and-dfdu-in-pancreatic-cancer-patients-using-an-optimal-design-sparse-sampling-approach
#14
Cindy Serdjebi, Florence Gattacceca, Jean-François Seitz, Francine Fein, Johan Gagnière, Eric François, Abakar Abakar-Mahamat, Gael Deplanque, Madani Rachid, Bruno Lacarelle, Joseph Ciccolini, Laetitia Dahan
BACKGROUND: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population pharmacokinetics approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols...
March 24, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28345463/computational-and-mechanistic-studies-on-the-effect-of-galactoxyloglucan-imatinib-nanoconjugate-in-imatinib-resistant-k562-cells
#15
Alphy Rose James, B S Unnikrishnan, R Priya, Manu M Joseph, T K Manojkumar, K Raveendran Pillai, R Shiji, G U Preethi, P Kusumakumary, T T Sreelekha
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344555/drug-repurposing-of-the-anthelmintic-niclosamide-to-treat-multidrug-resistant-leukemia
#16
Sami Hamdoun, Philipp Jung, Thomas Efferth
Multidrug resistance, a major problem that leads to failure of anticancer chemotherapy, requires the development of new drugs. Repurposing of established drugs is a promising approach for overcoming this problem. An example of such drugs is niclosamide, a known anthelmintic that is now known to be cytotoxic and cytostatic against cancer cells. In this study, niclosamide showed varying activity against different cancer cell lines. It revealed better activity against hematological cancer cell lines CCRF-CEM, CEM/ADR5000, and RPMI-8226 compared to the solid tumor cell lines MDA-MB-231, A549, and HT-29...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28341403/thiazolidine-derivatives-as-potent-and-selective-inhibitors-of-the-pim-kinase-family
#17
Carole J R Bataille, Méabh B Brennan, Simon Byrne, Stephen G Davies, Matthew Durbin, Oleg Fedorov, Kilian V M Huber, Alan M Jones, Stefan Knapp, Gu Liu, Anna Nadali, Camilo E Quevedo, Angela J Russell, Roderick G Walker, Robert Westwood, Graham M Wynne
The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases...
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28340541/drug-discovery-testing-compounds-in-patients-samples-by-automated-flow-cytometry
#18
Pilar Hernández, Julián Gorrochategui, Daniel Primo, Alicia Robles, José Luis Rojas, Ana Belén Espinosa, Cristina Gómez, Joaquín Martínez-López, Teresa A Bennett, Joan Ballesteros
Functional ex vivo assays that predict a patient's clinical response to anticancer drugs for guiding cancer treatment have long been a goal, but few have yet proved to be reliable. To address this, we have developed an automated flow cytometry platform for drug screening that evaluates multiple endpoints with a robust data analysis system that can capture the complex mechanisms of action across different compounds. This system, called PharmaFlow, is used to test peripheral blood or bone marrow samples from patients diagnosed with hematological malignancies...
March 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28339079/a-p110%C3%AE-specific-inhibitor-combined-with-bortezomib-blocks-drug-resistance-properties-of-ebv-related-b-cell-origin-cancer-cells-via-regulation-of-nf-%C3%AE%C2%BAb
#19
Ga Bin Park, Yoon Hee Chung, Jee-Yeong Jeong, Daejin Kim
Epstein-Barr virus (EBV) infection is closely related to carcinogenesis of various cancers, and is also associated with the development of drug resistance in cancer stem cells. However, in EBV-positive cancer cells, the mechanistic details of the downstream signaling and the connection of PI3K with the NF-κB pathway for development of drug resistance remain controversial. Diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM) cells infected by EBV display drug resistance-related proteins (MDR1, MRP1 and MRP2) and stem cell markers (OCT4 and SOX2)...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28327055/the-evaluation-of-the-anti-cancer-activity-of-ixazomib-on-caco2-colon-solid-tumor-cells-comparison-with-bortezomib
#20
Selin Engür, Miriş Dikmen
Proteasome inhibition has recently emerged as a clinically effective anticancer therapeutic approach. The first proteasome inhibitor, bortezomib (Velcade, PS-341), and new proteasome inhibitors including ixazomib have become more important in the development of targeted cancer therapies. Under physiological conditions, MLN9708 (ixazomib citrate), the stable citrate ester drug substance, hydrolyzes rapidly to MLN2238 (ixazomib), the biologically active boronic acid. It is a second-generation proteasome inhibitor, similar to the well-known proteasome inhibitor bortezomib, which is currently being investigated in phase 3 trials as a treatment for multiple Myeloma...
March 22, 2017: Acta Clinica Belgica
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