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https://www.readbyqxmd.com/read/28647477/derivatives-of-alkyl-gallate-triphenylphosphonium-exhibit-antitumor-activity-in-a-syngeneic-murine-model-of-mammary-adenocarcinoma
#1
Liliana Peredo-Silva, Sebastián Fuentes-Retamal, Cristian Sandoval-Acuña, Mario Pavani, Juan D Maya, Vicente Castro-Castillo, Matías Madrid-Rojas, Solange Rebolledo, Ulrike Kemmerling, Eduardo Parra, Jorge Ferreira
We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP(+)C8, TPP(+)C10 and TPP(+)C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP(+)C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells...
June 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28645565/from-the-outside-from-within-biological-and-therapeutic-relevance-of-signal-transduction-in-t-cell-acute-lymphoblastic-leukemia
#2
REVIEW
Mariana L Oliveira, Padma Akkapeddi, Isabel Alcobia, Afonso R Almeida, Bruno A Cardoso, Rita Fragoso, Teresa L Serafim, João T Barata
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from clonal expansion of transformed T-cell precursors. In this review we summarize the current knowledge on the external stimuli and cell-intrinsic lesions that drive aberrant activation of pivotal, pro-tumoral intracellular signaling pathways in T-cell precursors, driving transformation, leukemia expansion, spread or resistance to therapy. In addition to their pathophysiological relevance, receptors and kinases involved in signal transduction are often attractive candidates for targeted drug development...
June 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28640657/retinal-findings-on-oct-in-systemic-conditions
#3
Preeti Patil Chhablani, Vikas Ambiya, Akshay G Nair, Sailaja Bondalapati, Jay Chhablani
PURPOSE: Imaging technology has advanced by leaps and bounds in the recent past and has resulted in a much greater understanding of ocular diseases. The aim of this review article is to summarize optical coherence tomography (OCT) findings of various systemic conditions. METHOD: A systematic literature search of the Medline/PubMed database was performed. English articles up to April 2015 were included. Terms used for search included: Alzheimer's Disease; Multiple Sclerosis; Parkinson's Disease; Behçet's Disease; Schizophrenia; Migraine; Obstructive Sleep Apnea Syndrome; Neurofibromatosis; Sickle Cell Disease; Renal diseases; Lupus Retinopathy; Valsalva Retinopathy; Whiplash Retinopathy; Shaken-Baby Syndrome; Choroidal metastases; Intracranial Hypertension; Drug toxicity; Deferoxamine; Sildenafil; Tamoxifen; Hydroxychloroquine; Chloroquine; Ethambutol; Lead; Sickle Cell Disease; and Thalassemia along with OCT...
June 22, 2017: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/28630120/selinexor-induced-thrombocytopenia-results-from-inhibition-of-thrombopoietin-signaling-in-early-megakaryopoiesis
#4
Kellie R Machlus, Stephen K Wu, Prakrith Vijey, Thomas S Soussou, Zhi-Jian Liu, Eran Shacham, T J Unger, Trinayan Kashyap, Boris Klebanov, Martha Sola-Visner, Marsha Crochiere, Joseph E Italiano, Yosef Landesman
Selinexor is the first oral Selective Inhibitor of Nuclear Export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (NCT03071276, NCT02343042, NCT02227251, NCT03110562, NCT02606461). While selinexor shows promising efficacy, its primary adverse effect is high-grade thrombocytopenia. Therefore, we aimed to identify the mechanism of selinexor-induced thrombocytopenia to relieve it and improve its clinical management...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28627385/advances-in-antibody-drug-conjugates-a-new-era-of-targeted-cancer-therapy
#5
REVIEW
Samaresh Sau, Hashem O Alsaab, Sushil Kumar Kashaw, Katyayani Tatiparti, Arun K Iyer
Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28625826/drug-discovery-and-therapeutic-delivery-for-the-treatment-of-b-and-t-cell-tumors
#6
Regan Stephenson, Ankur Singh
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28623609/administration-of-direct-oral-anticoagulants-in-patients-with-myeloproliferative-neoplasms
#7
Jean-Christophe Ianotto, Marie-Anne Couturier, Hubert Galinat, Dominique Mottier, Christian Berthou, Gaëlle Guillerm, Eric Lippert, Aurélien Delluc
Direct oral anticoagulants (DOACs) have been approved to treat and prevent thrombotic events. However, they are not yet labeled for use in patients with active cancers. Myeloproliferative neoplasms (MPNs) are clonal chronic disorders with a high incidence of thrombotic events, for which low-dose aspirin (LDA) is the standard drug treatment. We analyzed efficacy and safety of DOACs prescription in patients treated for MPNs. An MPN database, the OBENE registry, was established at our institution. We collected biological and clinical data from diagnosis to last follow-up for every patient included in this study...
June 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28611451/beta-sitosterol-and-daucosterol-phytosterols-identified-in-grewia-tiliaefolia-perturbs-cell-cycle-and-induces-apoptotic-cell-death-in-a549-cells
#8
Tamilselvam Rajavel, Ramar Mohankumar, Govindaraju Archunan, Kandasamy Ruckmani, Kasi Pandima Devi
Lung cancer is the leading cause of cancer related deaths both in developed and developing countries. Since majority of the existing therapeutic methods harms both normal and malignant cells, a viable alternative is to switch into safe and beneficial traditional medicinal plants. Hence the present study was framed to identify selective anti-lung cancer agents from the medicinal plant Grewia tiliaefolia (GT). Cell viability experiments showed that benzene extract of GT (BGT) leaf effectively inhibited the growth of A549 cells, while being non-toxic to normal human lung L132 and PBMC cells...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610775/cytotoxic-effect-of-a-novel-naphthylchalcone-against-multiple-cancer-cells-focusing-on-hematologic-malignancies
#9
Mariana Franzoni Maioral, Camila do Nascimento Bodack, Natália Marceli Stefanes, Álisson Bigolin, Alessandra Mascarello, Louise Domeneghini Chiaradia-Delatorre, Rosendo Augusto Yunes, Ricardo José Nunes, Maria Cláudia Santos-Silva
Chalcones are natural compounds described in the literature by its several properties including cytotoxic activity against several tumor types. Considering that the search for new chemotherapeutic agents is still necessary, the aim of this study was to investigate the cytotoxic mechanisms involved in cell death induced by a synthetic chalcone (A23) on different tumor cells. Chalcone A23 reduced the cell viability of twelve tumor cell lines in a concentration and time dependent manner and it was more cytotoxic against acute leukemia cells...
June 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28599251/trehalose-enhances-the-antitumor-potential-of-methotrexate-against-mice-bearing-ehrlich-ascites-carcinoma
#10
Mohammed A El-Magd, Abeer Khamis, Samah K Nasr Eldeen, Wafaa M Ibrahim, Afrah F Salama
Methotrexate (MTX) is commonly used as a standard chemotherapy for many cancers, however its usage required high doses thereby leading to severe adverse effects. In a trial to find a suitable neoadjuvant therapy to decrease MTX dosage without lowering its chemotherapeutic efficacy, we investigated the antitumor effect of trehalose (TRE) on mice bearing Ehrlich ascites carcinoma (EAC) and checked whether TRE can enhance the antitumor potential of MTX. Treatment with TRE induced anti-tumor effects against EAC as reveled by a remarkable decrease in body weight, tumor volume, count of viable tumor cells, expression of the anti-apoptotic gene Bcl2 as well as by a significant increase in mean survival time, life span and expression of the apoptotic gene caspase-3...
June 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596938/genome-edited-t-cell-therapies
#11
REVIEW
Juliette M K M Delhove, Waseem Qasim
PURPOSE OF REVIEW: Alternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28592624/prolonged-pemetrexed-infusion-plus-gemcitabine-in-refractory-metastatic-colorectal-cancer-preclinical-rationale-and-phase-ii-study-results
#12
Alessandro Passardi, Francesca Fanini, Livia Turci, Flavia Foca, Paola Rosetti, Silvia Ruscelli, Andrea Casadei Gardini, Martina Valgiusti, Claudio Dazzi, Maurizio Marangolo
LESSONS LEARNED: Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged. BACKGROUND: We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28592260/recent-advances-in-the-use-of-pi3k-inhibitors-for-glioblastoma-multiforme-current-preclinical-and-clinical-development
#13
REVIEW
Hua-Fu Zhao, Jing Wang, Wei Shao, Chang-Peng Wu, Zhong-Ping Chen, Shing-Shun Tony To, Wei-Ping Li
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism...
June 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28586007/apg-1252-12a-induces-mitochondria-dependent-apoptosis-through-inhibiting-the-antiapoptotic-proteins-bcl-2-bcl-xl-in-hl-60-cells
#14
Jing Wang, Dajun Yang, Qiuyun Luo, Miaozhen Qiu, Lin Zhang, Baoxia Li, Haibo Chen, Hanjie Yi, Xianglei Yan, Shuxia Li, Jian Sun
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers...
June 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28572727/organic-effects-of-associating-paclitaxel-with-a-lipid-based-nanoparticle-system-on-a-nonhuman-primate-cebus-apella
#15
Danielle Cristinne Azevedo Feio, Nayara Cristina Lima de Oliveira, Edmundo Luis Rodrigues Pereira, Aleksandra Tiemi Morikawa, José Augusto Pereira Carneiro Muniz, Raquel Carvalho Montenegro, Ana Paula Negreiros Nunes Alves, Patrícia Danielle Lima de Lima, Raul Cavalcante Maranhão, Rommel Rodríguez Burbano
Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m(2)) and three with higher (250 mg/m(2)) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#16
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547805/quality-and-impact-of-eviq-cancer-treatments-online-www-eviq-org-au-the-medical-oncologist-s-perspective
#17
Lydia P Y Loke, Tina Y T Chen, Craig R Lewis, Robyn L Ward, Shelley A Rushton, Jeremy D Shapiro
INTRODUCTION: eviQ Cancer Treatments Online is a free, web-based resource providing access to over 600 evidence-based treatment protocols in medical oncology, radiation oncology, hematology and cancer genetics. With over 60 000 registrants from 148 countries, eviQ is widely used by cancer clinicians globally. The aim of this study was to examine the perceived quality of eviQ by Australian medical oncologists, the impact it had on their knowledge and practice, and the effect it had on their patients...
May 25, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28536803/prospective-multicenter-phase-ii-study-of-gemcitabine-plus-cisplatin-in-patients-with-unresectable-gallbladder-cancer
#18
Yoshiki Hirooka, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Koji Nonogaki, Akira Kanamori, Takanori Hirai, Hiroki Uchida, Osamu Shirai, Hideki Ishikawa, Hidemi Goto
PURPOSE: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC). METHODS: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m(2)) and cisplatin (25 mg/m(2)) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]...
May 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28533175/dendrimer-encapsulated-and-conjugated-delivery-of-berberine-a-novel-approach-mitigating-toxicity-and-improving-in-vivo-pharmacokinetics
#19
Lokesh Gupta, Ashok Kumar Sharma, Avinash Gothwal, Mohammed Shahid Khan, Mahaveer Prasad Khinchi, Arem Qayum, Shashank Kumar Singh, Umesh Gupta
Berberine (BBR) is a nitrogenous cyclic natural alkaloid with potential anticancer activity. However it has been less explored due to its poor pharmacokinetic profile. Dendrimers (e.g. PAMAM) have promising potential to deliver anticancer drugs/bio-actives because of their well-defined architecture, monodispersity and tailor-made surface functionality. In the present study it was attempted to deliver berberine through G4 PAMAM dendrimers by conjugation (BPC) as well as encapsulation (BPE) approach. The developed encapsulated and conjugated berberine formulations were found to have size in the approximate range of 100-200nm while zeta potential was almost same as PAMAM G4 dendrimer...
May 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28529947/immune-checkpoint-blockade-for-hematologic-malignancies-a-review
#20
REVIEW
Matthew J Pianko, Yuzhou Liu, Srishti Bagchi, Alexander M Lesokhin
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME)...
2017: Stem Cell Investigation
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