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https://www.readbyqxmd.com/read/29776346/a-systematic-review-of-the-risk-factors-for-clinical-response-to-opioids-for-all-age-patients-with-cancer-related-pain-and-presentation-of-the-paediatric-stop-pain-study
#1
Ersilia Lucenteforte, Laura Vagnoli, Alessandra Pugi, Giada Crescioli, Niccolò Lombardi, Roberto Bonaiuti, Maurizio Aricò, Sabrina Giglio, Andrea Messeri, Alessandro Mugelli, Alfredo Vannacci, Valentina Maggini
BACKGROUND: Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients. METHODS: We conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#2
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772694/the-nf-%C3%AE%C2%BAb-activating-pathways-in-multiple-myeloma
#3
REVIEW
Payel Roy, Uday Aditya Sarkar, Soumen Basak
Multiple myeloma(MM), an incurable plasma cell cancer, represents the second most prevalent hematological malignancy. Deregulated activity of the nuclear factor kappaB (NF-κB) family of transcription factors has been implicated in the pathogenesis of multiple myeloma. Tumor microenvironment-derived cytokines and cancer-associated genetic mutations signal through the canonical as well as the non-canonical arms to activate the NF-κB system in myeloma cells. In fact, frequent engagement of both the NF-κB pathways constitutes a distinguishing characteristic of myeloma...
May 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29759975/restoring-the-switch-for-cancer-cell-death-targeting-the-apoptosis-signaling-pathway
#4
REVIEW
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29759486/inhibition-of-hdacs-epha2-signaling-axis-with-ww437-demonstrates-promising-preclinical-antitumor-activity-in-breast-cancer
#5
Tao Zhang, Jingjie Li, Xiaojun Ma, Yang Yang, Wei Sun, Wangrui Jin, Lei Wang, Yuan He, Feifei Yang, Zhengfang Yi, Yingqi Hua, Mingyao Liu, Yihua Chen, Zhengdong Cai
Histone deacetylase inhibitors (HDACi) are small molecules targeting epigenetic enzymes approved for hematologic neoplasms, which have also demonstrated clinical activities in solid tumors. In our present study, we screened our internal compound library and discovered a novel HDACi, WW437, with potent anti-breast cancer ability in vitro and in vivo. WW437 significantly inhibited phosphorylated EphA2 and EphA2 expression. Further study demonstrated WW437 blocked HDACs-EphA2 signaling axis in breast cancer. In parallel, we found that EphA2 expression positively correlates with breast cancer progression; and combined use of WW437 and an EphA2 inhibitor (ALW-II-41-27) exerted more remarkable effect on breast cancer growth than either drug alone...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29757258/lipid-nanoparticles-decorated-with-tnf-related-aptosis-inducing-ligand-trail-are-more-cytotoxic-than-soluble-recombinant-trail-in-sarcoma
#6
Ana Gallego-Lleyda, Diego De Miguel, Alberto Anel, Luis Martinez-Lostao
Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells...
May 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29751792/discovering-novel-snps-that-are-correlated-with-patient-outcome-in-a-singaporean-cancer-patient-cohort-treated-with-gemcitabine-based-chemotherapy
#7
Vachiranee Limviphuvadh, Chee Seng Tan, Fumikazu Konishi, Piroon Jenjaroenpun, Joy Shengnan Xiang, Yuliya Kremenska, Yar Soe Mu, Nicholas Syn, Soo Chin Lee, Ross A Soo, Frank Eisenhaber, Sebastian Maurer-Stroh, Wei Peng Yong
BACKGROUND: Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients. METHODS: Using a pathway approach that incorporates comprehensive protein-protein interaction data to systematically extend the gemcitabine pharmacologic pathway, we identified 77 related nsSNPs, common in the Singaporean population...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29749542/the-hdac6-inhibitor-acy%C3%A2-1215-enhances-the-anticancer-activity-of-oxaliplatin-in-colorectal-cancer-cells
#8
Dong Hoon Lee, Hye-Rim Won, Hyun-Wook Ryu, Jung Min Han, So Hee Kwon
ACY‑1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY‑1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY‑1215 and anticancer agents in hematological cancers could occur in solid tumors...
May 11, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29748012/a-phase-i-study-of-nintedanib-combined-with-cisplatin-gemcitabine-as-first-line-therapy-for-advanced-squamous-non-small-cell-lung-cancer-lume-lung-3
#9
Martin Forster, Allan Hackshaw, Tommaso De Pas, Manuel Cobo, Pilar Garrido, Yvonne Summers, Anne-Marie C Dingemans, Michael Flynn, David Schnell, Ute von Wangenheim, Arsene-Bienvenu Loembé, Rolf Kaiser, Siow Ming Lee
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2 , Day 1), gemcitabine (1250 mg/m2 , Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs)...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29747654/bcl-2-as-therapeutic-target-for-hematological-malignancies
#10
REVIEW
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29746793/high-throughput-flow-cytometry-identifies-small-molecule-inhibitors-for-drug-repurposing-in-t-all
#11
Dominique R Perez, Christian K Nickl, Anna Waller, Cristina Delgado-Martin, Travis Woods, Nitesh D Sharma, Michelle L Hermiston, Mignon L Loh, Stephen P Hunger, Stuart S Winter, Alexandre Chigaev, Bruce Edwards, Larry A Sklar, Ksenia Matlawska-Wasowska
Kinase inhibitors have dramatically increased patient survival in a multitude of cancers, including hematological malignancies. However, kinase inhibitors have not yet been integrated into current clinical trials for patients with T-cell-lineage acute lymphoblastic leukemia (T-ALL). In this study, we used a high-throughput flow cytometry (HTFC) approach to test a collection of small-molecule inhibitors, including 26 FDA-approved tyrosine kinase inhibitors in a panel of T-ALL cell lines and patient-derived xenografts...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29745272/extracellular-vesicles-in-hematological-malignancies
#12
Zofia Litwińska, Karolina Łuczkowska, Bogusław Machaliński
Extracellular vesicles (EVs) act as transporters that carry regulatory molecules between cells in physiologic and pathologic states; therefore, they play a crucial role in thrombosis, inflammation, angiogenesis, vascular dysfunction and other processes that affect the course of hematologic diseases. Within the tumor microenvironment, for example the leukemic bone marrow, EVs-mediated signaling may direct the activities of surrounding cells and act as a positive feedback loop that contributes to cancer progression...
May 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#13
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29731425/histone-deacetylase-11-is-an-%C3%AE%C2%B5-n-myristoyllysine-hydrolase
#14
Carlos Moreno-Yruela, Iacopo Galleano, Andreas S Madsen, Christian A Olsen
Histone deacetylase (HDAC) enzymes regulate diverse biological function, including gene expression, rendering them potential targets for intervention in a number of diseases, with a handful of compounds approved for treatment of certain hematologic cancers. Among the human zinc-dependent HDACs, the most recently discovered member, HDAC11, is the only member assigned to subclass IV. It is the smallest protein and has the least well understood biological function. Here, we show that HDAC11 cleaves long-chain acyl modifications on lysine side chains with remarkable efficiency...
April 23, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29726787/role-of-cyclin-dependent-kinase-4-6-inhibitors-in-the-current-and-future-eras-of-cancer-treatment
#15
S Parylo, A Vennepureddy, V Dhar, P Patibandla, A Sokoloff
Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29721665/status-and-future-directions-in-the-management-of-pancreatic-cancer-potential-impact-of-nanotechnology
#16
REVIEW
Catherine M Sielaff, Shaker A Mousa
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity...
May 2, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29721395/super-charged-nk-cells-inhibit-growth-and-progression-of-stem-like-poorly-differentiated-oral-tumors-in-vivo-in-humanized-blt-mice-effect-on-tumor-differentiation-and-response-to-chemotherapeutic-drugs
#17
Kawaljit Kaur, Paytsar Topchyan, Anna Karolina Kozlowska, Nick Ohanian, Jessica Chiang, Phyu Ou Maung, So-Hyun Park, Meng-Wei Ko, Changge Fang, Ichiro Nishimura, Anahid Jewett
Therapeutic role of NK cells in solid tumors was challenged previously even though their role in hematological malignancies has clearly been established. Furthermore, functions and numbers of NK cells are greatly suppressed in oral cancer patients necessitating effective future NK immunotherapeutic strategies to aid in the control of disease. The humanized-BLT (hu-BLT) mice were used to implant stem-like/undifferentiated oral tumors to study the role of super-charged NK cells with and without feeding with AJ2 probiotic bacteria...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721056/the-efficacy-and-toxicity-of-gefitinib-in-treating-non-small-cell-lung-cancer-a-meta-analysis-of-19-randomized-clinical-trials
#18
Hongmei Wo, Jing He, Yang Zhao, Hao Yu, Feng Chen, Honggang Yi
Background: This meta-analysis evaluated the efficacy and toxicity of gefitinib with other commonly used drugs in different treatment settings and epidermal growth factor receptor (EGFR) mutation status. Methods: Nineteen randomize clinical trials (RCTs) of 6,554 patients with NSCLC were pooled in this meta-analysis by random-effects or fixed-effects model, whichever is proper. Results: In first-line therapy, gefitinib showed higher odds than chemotherapy (OR = 2.19, 95% CI: 1.20-4.01), but less than other targeted therapies (OR = 0...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29710458/centaurea-albonitens-extract-enhances-the-therapeutic-effects-of-vincristine-in-leukemic-cells-by-inducing-apoptosis
#19
Forouzan Bahmani, Somayeh Esmaeili, Davood Bashash, Nasrin Dehghan-Nayeri, Pargol Mashati, Ahmad Gharehbaghian
Drug-induced toxicities and dose-related side effects are the major challenges in the conventional cancer therapy by the chemo drugs. On the other hand, herbal derivatives have obtained a great research interest in the field of therapeutic applications because of their more favorable specifications including less toxicity, cost-effective and more physiologically compatible than the chemical drugs. For this purpose, we evaluated methanolic extract prepared from Centaurea albonitens Turrill alone and in combination with Vincristine (VCR) for its potential cytotoxic effects in NALM-6, REH, NB4 and KMM-1 cell lines by using the various approaches...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29707520/dna-damage-inducible-transcript-4-gene-the-switch-of-the-metabolism-as-potential-target-in-cancer
#20
REVIEW
Indira Tirado-Hurtado, Williams Fajardo, Joseph A Pinto
DNA damage inducible transcript 4 ( DDIT4 ) gene is expressed under stress situations turning off the metabolic activity triggered by the mammalian target of rapamycin (mTOR). Several in vitro and in vivo works have demonstrated the ability of DDIT4 to generate resistance to cancer therapy. The link between the metabolism suppression and aggressiveness features of cancer cells remains poorly understood since anti-mTOR agents who are part of the repertoire of drugs used for systemic treatment of cancer achieving variable results...
2018: Frontiers in Oncology
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