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https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#1
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29143249/next-generation-chimeric-antigen-receptor-t-cell-therapy-going-off-the-shelf
#2
Marco Ruella, Saad S Kenderian
Autologous, patient-specific chimeric antigen receptor T-cell (CART) therapy has emerged as a powerful and potentially curative therapy for cancer, especially for CD19-positive hematological malignancies. Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy approved by the Food and Drug Administration (FDA) for acute lymphoblastic leukemia. However, the development of CART technology and its wider application is partly limited by the patient-specific nature of such a platform and by the time required for manufacturing...
November 16, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29142069/cat-02-106-a-site-specifically-conjugated-anti-cd22-antibody-bearing-an-mdr1-resistant-maytansine-payload-yields-excellent-efficacy-and-safety-in-preclinical-models
#3
Penelope M Drake, Adam Carlson, Jesse M McFarland, Stefanie Banas, Robyn M Barfield, Wesley Zmolek, Yun Cheol Kim, Betty C B Huang, Romas Kudirka, David Rabuka
Hematologically-derived tumors make up ~10% of all newly-diagnosed cancer cases in the U.S. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#4
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135093/evaluation-of-safety-of-bevacizumab-as-second-line-treatment-of-patients-with-metastatic-colorectal-cancer
#5
Vladimir Todorovic, Nada Cicmil Saric, Jadranka Lakicevic, Milan Sorat
PURPOSE: Bevacizumab is a relatively new monoclonal antibody introduced in the treatment of metastatic colorectal cancer (CRC). Since varied efficiency and adverse events of this drug were reported, the purpose of this study was to assess the safety of bevacizumab as second-line treatment of patients with metastatic CRC. METHODS: This observational, non-interventional study involved 35 patients with metastatic CRC treated with bevacizumab. Patients were from the Oncology Clinic, Clinical Centre of Montenegro...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134637/ercc4-regulatory-variant-predict-grade-3-or-4-toxicities-in-patients-with-advanced-non-small-cell-lung-cancer-treated-by-platinum-based-therapy
#6
Ruoxin Zhang, Ming Jia, Yuan Xu, Danwen Qian, Mengyun Wang, Meiling Zhu, Menghong Sun, Jianhua Chang, Qingyi Wei
Platinum-based chemotherapy (PBC) in combination with the 3(rd) generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts, contributing to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in eight NER core genes with overall, gastrointestinal and hematologic toxicities...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29133776/tacrolimus-levels-are-not-associated-with-risk-of-malignancy-in-lung-transplant-recipients
#7
Benjamin Daniel Fox, Fadi Ashquar, Yael Raviv, Dror Rozengarten, Osnat Straichman, Shimon Izhakian, Mordechai Reuven Kramer
BACKGROUND Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. MATERIAL AND METHODS The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer...
November 14, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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
#8
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/29129089/systemic-therapy-for-esophageal-cancer-chemotherapy
#9
Geoffrey Y Ku
As one-half of patients with esophagogastric cancer (EGC) present with metastatic disease and the majority of patients with locally advanced disease will eventually develop metastatic disease despite multimodality therapy, most patients will receive palliative chemotherapy at some point. The reference first-line regimen consists of a fluoropyrimidine/platinum combination, which is the standard in East Asia, where this disease is endemic. Options include infusional 5-fluorouracil (5-FU), capecitabine, S-1 and other oral 5-FU pro-drugs and cisplatin or oxaliplatin...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29127862/frondoside-a-potentiates-the-effects-of-conventional-therapeutic-agents-in-acute-leukemia
#10
F H Sajwani, P Collin, T E Adrian
Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy...
November 8, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29124327/a-phase-ii-study-of-biweekly-gemcitabine-and-carboplatin-in-completely-resected-stage-ib-iiia-non-small-cell-lung-cancer
#11
Reiko Sakurai, Yoshio Tomizawa, Akihiro Yoshii, Yosuke Miura, Hiroaki Tsurumaki, Kyoichi Kaira, Noriaki Sunaga, Osamu Kawashima, Takeshi Hisada, Masanobu Yamada, Ryusei Saito
PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of biweekly gemcitabine and carboplatin combination treatment in patients with resected non-small cell lung cancer (NSCLC). METHODS: Patients with completely resected stage IB to IIIA NSCLC were treated with four cycles of gemcitabine (1000 mg/m(2), days 1 and 15) plus carboplatin [area under the time-concentration curve (AUC) 5 mg/mL/min, day 1] every 4 weeks as adjuvant chemotherapy...
November 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29113203/distribution-of-uridine-diphosphate-glucuronosyltransferase-1a-polymorphisms-and-their-role-in-irinotecan-induced-toxicity-in-patients-with-cancer
#12
Yang Wang, Cuihua Yi, Yawei Wang, Hui Li, Bei Li, Dan Wang, Jintong Du, Lian Liu, Xiuwen Wang
Uridine diphosphate glucuronosyltransferase 1A (UGT1A1), which affects irinotecan metabolism, has been associated with severe adverse reactions in patients with cancer treated with irinotecan. However, neither large-scale analysis of the distribution of UGT1A1 polymorphisms, nor standardized assessment of how UGT1A1 polymorphisms affect irinotecan treatment has been performed in China. The aim of the present study was to investigate the distribution of UGT1A1 polymorphisms (*28 and *6) in 2,093 Chinese patients with cancer who were treated with irinotecan from more than 15 hospitals in Shandong, to examine how the coexistence of UGT1A1*6 and UGT1A1*28 alleles may be able to predict toxicities induced by irinotecan in 105 of the patients, and to search for other relevant risk factors...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111982/management-of-immune-mediated-cytopenias-in-the-era-of-cancer-immunotherapy-a-report-of-4-cases
#13
Yamin Sun, Stephen K Lee, Thein H Oo, Cristhiam M Rojas-Hernandez
Recent advancements in immunotherapy have brought promising drugs to fight cancers; a subset of immunotherapy medications are known as checkpoint inhibitors. Their mechanism of action relies on upregulating antitumor response by reversing T-cell suppression; as a consequence the effect can also result in a spectrum of immune related complications. Reported complications to date include: skin, gastrointestinal mucosa, hypophysis, liver, endocrine system, nervous system, kidney, musculoskeletal system and the hematologic system...
November 3, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29109077/safety-and-efficacy-of-intratumoral-injections-of-chimeric-antigen-receptor-car-t-cells-in-metastatic-breast-cancer
#14
Julia Tchou, Yangbing Zhao, Bruce L Levine, Paul J Zhang, Megan M Davis, Jan Joseph Melenhorst, Irina Kulikovskaya, Andrea L Brennan, Xiajun Liu, Simon F Lacey, Avery Posey, Austin D Williams, Alycia So, Jose R Conejo-Garcia, Gabriela Plesa, Regina M Young, Shannon McGettigan, Jean Campbell, Robert H Pierce, Jennifer M Matro, Angela M DeMichele, Amy S Clark, Laurence J N Cooper, Lynn M Schuchter, Robert H Vonderheide, Carl H June
Chimeric antigen receptors (CARs) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ~50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602)...
November 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29108877/pim-kinases-from-survival-factors-to-regulators-of-cell-motility
#15
REVIEW
Niina M Santio, Päivi J Koskinen
PIM kinases are oncogenic serine/threonine kinases, the expression and activities of which are tightly regulated in normal tissues, but upregulated in many types of human malignancies, including both hematological and solid cancers. Since high PIM expression levels have been connected to cancer progression and poor patient survival, PIM kinases have become attractive targets for drug development. Many downstream targets have also been identified, through which PIM kinases promote cell survival, proliferation and metabolism...
November 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29104344/validation-of-a-machine-learning-approach-for-venous-thromboembolism-risk-prediction-in-oncology
#16
Patrizia Ferroni, Fabio M Zanzotto, Noemi Scarpato, Silvia Riondino, Fiorella Guadagni, Mario Roselli
Using kernel machine learning (ML) and random optimization (RO) techniques, we recently developed a set of venous thromboembolism (VTE) risk predictors, which could be useful to devise a web interface for VTE risk stratification in chemotherapy-treated cancer patients. This study was designed to validate a model incorporating the two best predictors and to compare their combined performance with that of the currently recommended Khorana score (KS). Age, sex, tumor site/stage, hematological attributes, blood lipids, glycemic indexes, liver and kidney function, BMI, performance status, and supportive and anticancer drugs of 608 cancer outpatients were all entered in the model, with numerical attributes analyzed as continuous values...
2017: Disease Markers
https://www.readbyqxmd.com/read/29102482/vitamin-c-a-new-player-in-regulation-of-the-cancer-epigenome
#17
REVIEW
Linn Gillberg, Andreas D Ørskov, Minmin Liu, Laurine B S Harsløf, Peter A Jones, Kirsten Grønbæk
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care...
November 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29098766/some-statistical-considerations-in-the-clinical-development-of-cancer-immunotherapies
#18
Bo Huang
Immuno-oncology has emerged as an exciting new approach to cancer treatment. Common immunotherapy approaches include cancer vaccine, effector cell therapy, and T-cell-stimulating antibody. Checkpoint inhibitors such as cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/L1 antagonists have shown promising results in multiple indications in solid tumors and hematology. However, the mechanisms of action of these novel drugs pose unique statistical challenges in the accurate evaluation of clinical safety and efficacy, including late-onset toxicity, dose optimization, evaluation of combination agents, pseudoprogression, and delayed and lasting clinical activity...
November 2, 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/29080972/the-proteasome-and-myeloma-associated-bone-disease
#19
REVIEW
Fabrizio Accardi, Denise Toscani, Federica Costa, Franco Aversa, Nicola Giuliani
Bone disease is the hallmark of multiple myeloma (MM), a hematological malignancy characterized by osteolytic lesions due to a severe uncoupled and unbalanced bone remodeling with pronounced osteoblast suppression. Bone metastasis is also a frequent complication of solid tumors including advanced breast or prostate cancer. In the past years, the ubiquitin-proteasome pathway has been proved critical in regulating the balance between bone formation and bone resorption. Proteasome inhibitors (PIs) are a new class of drugs, currently used in the treatment of MM, that affect both tumor cells and bone microenvironment...
October 28, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29076761/cdk5-in-oncology-recent-advances-and-future-prospects
#20
Jimma Likisa Lenjisa, Solomon Tadesse, Nishat Zareen Khair, Malika Kumarasiri, Mingfeng Yu, Hugo Albrecht, Robert Milne, Shudong Wang
Selective abrogation of cyclin-dependent kinases (CDK) activity is a highly promising strategy in cancer treatment. The atypical CDK, CDK5 has long been known for its role in neurodegenerative diseases, and is becoming an attractive drug target for cancer therapy. Myriads of recent studies have uncovered that aberrant expression of CDK5 contributes to the oncogenic initiation and progression of multiple solid and hematological malignancies. CDK5 is also implicated in the regulation of cancer stem cell biology...
October 2017: Future Medicinal Chemistry
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