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https://www.readbyqxmd.com/read/28081343/the-combined-effects-of-proteasome-inhibitor-bortezomib-with-topoisomerase-i-and-ii-inhibitors-on-topoisomerase-enzymes
#1
Emine Öksüzoğlu, Çiydem Tırınoğlu, Barış Kerimoğlu
BACKGROUND/AIM: DNA topoisomerases are ubiquitous enzymes that regulate conformational changes in DNA topology during essential cellular processes, and, for this reason, have been characterized as the cellular targets of a number of anticancer drugs. Bortezomib is a powerful proteasome inhibitor used in the treatment of hematological malignancies. In this study, we investigated the inhibitory effects of bortezomib on human topoisomerase I and II enzymes both alone and in combination modes with camptothecin and etoposide...
December 20, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28073680/rationale-and-design-of-pemvitastart-an-open-label-randomized-trial-comparing-simultaneous-versus-standard-initiation-of-vitamin-b12-and-folate-supplementation-in-nonsquamous-non-small-cell-lung-cancer-patients-undergoing-first-line-pemetrexed-based-chemotherapy
#2
Milind Baldi, Digambar Behera, Jyotdeep Kaur, Rakesh Kapoor, Navneet Singh
Pemetrexed is the preferred chemotherapeutic drug for nonsquamous, non-small-cell lung cancer patients whenever the predictive molecular biomarkers for targeted therapy have either not been assessed or are absent. As per manufacturers' instructions, supplementation with folic acid (FA; folate) at a dose of 350 to 1000 μg daily should be started seven days before the first dose of pemetrexed-based chemotherapy and continued during therapy and for 21 days after therapy cessation. Vitamin B12 injections (1000 μg intramuscularly) should also be started one week before the first dose of chemotherapy...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28069724/synthetic-lethality-exploitation-by-an-anti-trop-2-sn-38-antibody-drug-conjugate-immu-132-plus-parp-inhibitors-in-brca1-2-wild-type-triple-negative-breast-cancer
#3
Thomas M Cardillo, Robert M Sharkey, Diane L Rossi, Roberto Arrojo, Ali Mostafa, David M Goldenberg
PURPOSE: Both Poly(ADP-ribose) polymerase inhibitors (PARPi) and sacituzumab govitecan (IMMU-132) are currently under clinical evaluation in triple-negative breast cancer (TNBC). We sought to investigate the combined DNA-damaging effects of the topoisomerase I (Topo I)-inhibitory activity of IMMU-132 with PARPi disruption of DNA repair in TNBC. EXPERIMENTAL DESIGN: In vitro, human TNBC cell lines were incubated with IMMU-132 and various PARPi (olaparib, rucaparib, or talazoparib) to determine the effect on growth, double-stranded DNA (dsDNA) breaks, and cell-cycle arrest...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28065395/serial-retrograde-instillations-of-sustained-release-formulation-of-mitomycin-c-to-the-upper-urinary-tract-of-the-yorkshire-swine-using-a-thermosensitive-polymer-safety-and-feasibility
#4
Nicholas M Donin, Dalit Strauss-Ayali, Yael Agmon-Gerstein, Nadav Malchi, Andrew T Lenis, Stuart Holden, Allan J Pantuck, Arie S Belldegrun, Karim Chamie
BACKGROUND: MitoGel is a novel drug formulation intended for the treatment of upper tract urothelial cancer with proven feasibility and safety in an animal model. OBJECTIVE: To evaluate the feasibility, safety, toxicokinetics, and histologic changes associated with serial retrograde MitoGel instillations to the upper urinary tract in a swine model. DESIGN, SETTING, AND PARTICIPANTS: Overall, 27 Yorkshire swine underwent 6 once-weekly unilateral retrograde instillations of MitoGel...
January 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28061451/nanoparticle-albumin-bound-paclitaxel-as-neoadjuvant-chemotherapy-of-breast-cancer-a-systematic-review-and-meta-analysis
#5
REVIEW
Yu Zong, Jiayi Wu, Kunwei Shen
BACKGROUND: The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain. METHODS: Both electronic databases and proceedings of oncologic meetings were included in systematic literature search. Pooled rates of pathological complete response (pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060337/using-rna-sequencing-to-detect-novel-splice-variants-related-to-drug-resistance-in-in-vitro-cancer-models
#6
Rocco Sciarrillo, Anna Wojtuszkiewicz, Irsan E Kooi, Valentina E Gómez, Ugo Boggi, Gerrit Jansen, Gert-Jan Kaspers, Jacqueline Cloos, Elisa Giovannetti
Drug resistance remains a major problem in the treatment of cancer for both hematological malignancies and solid tumors. Intrinsic or acquired resistance can be caused by a range of mechanisms, including increased drug elimination, decreased drug uptake, drug inactivation and alterations of drug targets. Recent data showed that other than by well-known genetic (mutation, amplification) and epigenetic (DNA hypermethylation, histone post-translational modification) modifications, drug resistance mechanisms might also be regulated by splicing aberrations...
December 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28056114/diagnosis-and-management-of-waldenstr%C3%A3-m-macroglobulinemia-mayo-stratification-of-macroglobulinemia-and-risk-adapted-therapy-msmart-guidelines-2016
#7
Prashant Kapoor, Stephen M Ansell, Rafael Fonseca, Asher Chanan-Khan, Robert A Kyle, Shaji K Kumar, Joseph R Mikhael, Thomas E Witzig, Michelle Mauermann, Angela Dispenzieri, Sikander Ailawadhi, A Keith Stewart, Martha Q Lacy, Carrie A Thompson, Francis K Buadi, David Dingli, William G Morice, Ronald S Go, Dragan Jevremovic, Taimur Sher, Rebecca L King, Esteban Braggio, Ann Novak, Vivek Roy, Rhett P Ketterling, Patricia T Greipp, Martha Grogan, Ivana N Micallef, P Leif Bergsagel, Joseph P Colgan, Nelson Leung, Wilson I Gonsalves, Yi Lin, David J Inwards, Suzanne R Hayman, Grzegorz S Nowakowski, Patrick B Johnston, Steven J Russell, Svetomir N Markovic, Steven R Zeldenrust, Yi L Hwa, John A Lust, Luis F Porrata, Thomas M Habermann, S Vincent Rajkumar, Morie A Gertz, Craig B Reeder
Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations: Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course...
January 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28050012/ppar-delta-promotes-survival-of-chronic-lymphocytic-leukemia-cells-in-energetically-unfavorable-conditions
#8
Y-J Li, L Sun, Y Shi, G Wang, X Wang, S Dunn, C Iorio, R A Screaton, D E Spaner
Targeting the mechanisms that allow Chronic Lymphocytic Leukemia (CLL) cells to survive in harsh cancer microenvironments should improve patient outcomes. The nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) sustains other cancers and in silico analysis showed higher PPARD expression in CLL cells than normal lymphocytes and other hematologic cancers. A direct association was found between PPARδ protein levels in CLL cells and clinical score. Transgenic expression of PPARδ increased the growth and survival of CD5(+) Daudi cells and primary CLL cells in stressful conditions including exhausted tissue culture media, low extracellular glucose, hypoxia, and exposure to cytotoxic drugs...
January 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28040066/effects-of-ambroxol-hydrochloride-on-concentrations-of-paclitaxel-and-carboplatin-in-lung-cancer-patients-at-different-administration-times
#9
J Li, W Yi, P Jiang, R Sun, T Li
Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration...
November 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28034349/biological-agents-in-rheumatoid-arthritis-a-cross-link-between-immune-tolerance-and-immune-surveillance
#10
Rossella Talotta, Fabiola Atzeni, Alberto Batticciotto, Maurizio Benucci, Sara Bongiovanni, Piercarlo Sarzi-Puttini
The biological drugs have all been successfully used to treat rheumatoid arthritis (RA) and have led to fair rates of clinical remission; however, the possible occurrence of adverse events such as infectious diseases or cancers means that the patients undergoing treatment need to be closely monitored. Anti-TNF agents, first appeared in the pharmacological algorithm of RA in the early 2000s, seem to lead to a higher risk of reactivated tubercular infection than the biological agents with different mechanism of action (abatacept or rituximab)...
December 30, 2016: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/28001402/anticancer-and-antiangiogenic-iron-ii-complexes-that-target-thioredoxin-reductase-to-trigger-cancer-cell-apoptosis
#11
Lina Xie, Zuandi Luo, Zhennan Zhao, Tianfeng Chen
Thioredoxin reductase (TrxR) is a selenoenzyme that could regulate intracellular oxidative balance and found to be overexpressed in many human tumor cells. Due to its important role in cancer progression, TrxR is becoming an attractive target in chemotherapeutic drug design. In this study, a new class of Fe(II) complexes with phenanthroline derivatives as ligands were synthesized and characterized. The mechanism of cell death induced by complex 3 revealed that the growth of cancer cells was suppressed by apoptosis and specifically inhibited the activities of TrxR...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27978874/-concurrent-chemoradiotherapy-with-original-chemotherapy-regimens-may-not-be-suitable-for-patients-who-failed-to-respond-to-induction-chemotherapy%C3%A2-in-limited-stage-small-cell-lung-cancer
#12
Daquan Wang, Liming Xu, Lujun Zhao, Wencheng Zhang, Qingsong Pang, Ningbo Liu, Xi Chen, Xiuli Chen, Zhiyong Yuan, Ping Wang
BACKGROUND: The group of small cell lung cancer (SCLC) are usually highly sensitive to chemotherapy, and less than 15% of them are resistant to drugs. We respectively evaluate the correlation of the sequence and timing of radiotherapy with progression-free survival (PFS) and overall survival (OS) in patients with limited-stage SCLC (LS-SCLC), and to figure out whether concurrent chemoradiotherapy is superior to sequent chemoradiotherapy. METHODS: Sixty-seven patients diagnosed with LS-SCLC from January 2009 to June 2014 failed to respond to induction chemotherapy...
December 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27931828/targeting-mtor-pathway-in-gynecological-malignancies-biological-rationale-and-systematic-review-of-published-data
#13
REVIEW
Loay Kassem, Omar Abdel-Rahman
BACKGROUND: mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers. METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27925256/pharmacokinetic-drug-drug-interactions-of-tyrosine-kinase-inhibitors-a-focus-on-cytochrome-p450-transporters-and-acid-suppression-therapy
#14
REVIEW
Caroline Gay, Delphine Toulet, Pascal Le Corre
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed...
December 7, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#15
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#16
Jean-Pascal Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
December 2016: Oncologist
https://www.readbyqxmd.com/read/27900832/bromodomain-and-extraterminal-protein-inhibitors-in-pediatrics-a-review-of-the-literature
#17
REVIEW
Irene Jiménez, André Baruchel, François Doz, Johannes Schulte
The last few years have seen the identification of pharmacologic approaches to target bromodomain and extraterminal (BET) proteins for cancer treatment. These proteins have an essential role in gene transcription regulation by binding acetylated lysine residues on histone tails, activating gene transcription. BET inhibitors have been tested in preclinical models including pediatric malignancies and several adult clinical trials are ongoing. Since the development of new drugs in pediatric cancer has long lagged behind programs for adults, the aim of this review is to show the importance of these therapies in pediatric malignancies to support their development in pediatric oncology/hematology...
November 30, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27896224/in-vitro-apoptotic-effects-of-farnesyltransferase-blockade-in-acute-myeloid-leukemia-cells
#18
V Giudice, P Ricci, L Marino, M Rocco, G Villani, M Langella, L Manente, E Seneca, I Ferrara, L Pezzullo, B Serio, C Selleri
Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs currently tested in phase I-II clinical trials for treatment of hematological malignancies. The in vitro effects of various FTIs (alpha-hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34(+) KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64 patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a significant inhibitory activity in CD34(+) KG1a and primary bone marrow (BM) leukemic cells from 56% of AML patients...
November 2016: Translational Medicine @ UniSa
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#19
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims Iii, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM)...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#20
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
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