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https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#1
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#2
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352505/p53-independent-noxa-induction-by-cisplatin-is-regulated-by-atf3-atf4-in-head-and-neck-squamous-cell-carcinoma-cells
#3
Kanika Sharma, Thien-Trang Vu, Wade Cook, Mitra Naseri, Kevin Zhan, Wataru Nakajima, Hisashi Harada
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family-dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of pro-apoptotic BCL-2 family protein, Noxa, that can bind to the pro-survival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death...
January 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29351194/involvement-of-bax-and-bcl-2-in-induction-of-apoptosis-by-essential-oils-of-three-lebanese-salvia-species-in-human-prostate-cancer-cells
#4
Alessandra Russo, Venera Cardile, Adriana C E Graziano, Rosanna Avola, Maurizio Bruno, Daniela Rigano
Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145). The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify necrosis cell death...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350659/thiopental-is-better-than-propofol-for-electroconvulsive-therapy
#5
Massimiliano Nuzzi, Dario Delmonte, Barbara Barbini, Laura Pasin, Ornella Sottocorna, Giuseppina Maria Casiraghi, Cristina Colombo, Giovanni Landoni, Alberto Zangrillo
BACKGROUND AND AIM OF THE WORK: electroconvulsive therapy is a psychiatric procedure requiring general anesthesia. The choice of the hypnotic agent is important because the success of the intervention is associated to the occurrence and duration of motor convulsion. However, all available anesthetic agents have anti-convulsant activity. We compared the effect of thiopental and propofol on seizures. METHODS: We designed a retrospective study at Mood Disorders Unit of a teaching Hospital...
January 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29349707/piperazine-clubbed-with-2-azetidinone-derivatives-suppresses-proliferation-migration-and-induces-apoptosis-in-human-cervical-cancer-hela-cells-through-oxidative-stress-mediated-intrinsic-mitochondrial-pathway
#6
Rashmin Khanam, Raj Kumar, Iram Iqbal Hejazi, Syed Shahabuddin, Ramovatar Meena, Vikrant Jayant, Prabhat Kumar, Abdul Roouf Bhat, Fareeda Athar
Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis...
January 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29348836/vitexin-confers-hsf-1-mediated-autophagic-cell-death-by-activating-jnk-and-apol1-in-colorectal-carcinoma-cells
#7
Monika Bhardwaj, Souren Paul, Rekha Jakhar, Imran Khan, Ji In Kang, Ho Min Kim, Jong Won Yun, Seon-Jin Lee, Hee Jun Cho, Hee Gu Lee, Sun Chul Kang
Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds. Vitexin, a natural flavonoid has been documented as a potent anti-tumor agent on various cell lines...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348564/inhibition-of-wnt-%C3%AE-catenin-signaling-under-serum-starvation-and-hypoxia-induces-adipocytic-transdifferentiation-in-human-leiomyoma-cells
#8
Hiroshi Harada, Yojiro Tsuda, Kei Yabuki, Eisuke Shiba, Kazuyoshi Uchihashi, Atsuji Matsuyama, Yoshihisa Fujino, Toru Hachisuga, Masanori Hisaoka
Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of β-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/β-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes β-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29348462/piperlongumine-and-p53-reactivator-apr-246-selectively-induce-cell-death-in-hnscc-by-targeting-gstp1
#9
Wei Hang, Zhi-Xian Yin, Gang Liu, Qinghua Zeng, Xiang-Feng Shen, Qian-Hui Sun, Dong-Dong Li, Yong-Ping Jian, Yang-He Zhang, Yi-Shu Wang, Cheng-Shi Quan, Rui-Xun Zhao, Yu-Lin Li, Zhi-Xiang Xu
TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1Met (also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29348128/pevonedistat-a-first-in-class-nedd8-activating-enzyme-nae-inhibitor-combined-with-azacitidine-in-patients-with-aml
#10
Ronan T Swords, Steven Coutre, Michael B Maris, Joshua F Zeidner, James M Foran, Jose Cruz, Harry P Erba, Jesus G Berdeja, Wayne Tam, Saran Vardhanabhuti, Iwona Pawlikowska-Dobler, Hélène M Faessel, Ajeeta B Dash, Farhad Sedarati, Bruce J Dezube, Douglas V Faller, Michael R Savona
Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study (NCT01814826) of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naïve AML, unfit for standard induction therapy, received PEV 20 or 30 mg/m2 IV on days 1, 3, and 5, combined with fixed-dose AZA (75 mg/m2 IV/SC) on days 1-5, 8, and 9, every 28 days...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29345347/interferons-and-beyond-induction-of-antiretroviral-restriction-factors
#11
REVIEW
Dominik Hotter, Frank Kirchhoff
Antiviral restriction factors are structurally and functionally diverse cellular proteins that play a key role in the first line of defense against viral pathogens. Although many cell types constitutively express restriction factors at low levels, their induction in response to viral exposure and replication is often required for potent control and repulse of the invading pathogens. It is well established that type I IFNs efficiently induce antiviral restriction factors. Accumulating evidence suggests that other types of IFN, as well as specific cytokines, such as IL-27, and other activators of the cell are also capable of enhancing the expression of restriction factors and hence to establish an antiviral cellular state...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345296/vitamin%C3%A2-d-derivatives-potentiate-the-anticancer-and-anti-angiogenic-activity-of-tyrosine-kinase-inhibitors-in-combination-with-cytostatic-drugs-in-an-a549-non-small-cell-lung-cancer-model
#12
Ewa Maj, Beata Filip-Psurska, Magdalena Milczarek, Mateusz Psurski, Andrzej Kutner, Joanna Wietrzyk
Numerous in vitro and in vivo studies have demonstrated that calcitriol [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity, regulating proliferation, differentiation and apoptosis, as well as angiogenesis. Vitamin D compounds have been shown to exert synergistic effects when used in combination with different agents used in anticancer therapies in different cancer models. The aim of this study was to evaluate the mechanisms of the cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI‑2191) and 1,25(OH)2D3] with tyrosine kinase inhibitors (imatinib and sunitinib) together with cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer model...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344262/hedyotis-diffusa-willd-extract-suppresses-colorectal-cancer-growth-through-multiple-cellular-pathways
#13
Jianyu Feng, Yiyi Jin, Jun Peng, Lihui Wei, Qiaoyan Cai, Zhaokun Yan, Zijun Lai, Jiumao Lin
The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342359/semiconducting-photothermal-nanoagonist-for-remote-controlled-specific-cancer-therapy
#14
Xu Zhen, Chen Xie, Yuyan Jiang, Xiangzhao Ai, Bengang Xing, Kanyi Pu
Nanomedicines have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally-responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29342279/incidence-and-predictors-of-post-transplant-lymphoproliferative-disease-after-kidney-transplantation-during-adulthood-and-childhood-a-registry-study
#15
Anna Francis, David W Johnson, Armando Teixeira-Pinto, Jonathan C Craig, Germaine Wong
Background: Differences in the epidemiology of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients remain unclear. Methods: Using the Australian and New Zealand Dialysis and Transplant Registry (1963-2015), the cumulative incidences of PTLD in children (age <20 years) and adults were calculated using a competing risk of death model and compared with age-matched population-based data using standardized incidence ratios (SIRs)...
January 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#16
Zuzana Papackova, Marie Heczkova, Helena Dankova, Eva Sticova, Alena Lodererova, Lenka Bartonova, Martin Poruba, Monika Cahova
Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination...
2018: PloS One
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#17
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341908/induction-of-au-methotrexate-conjugates-by-sugar-molecules-production-assembly-mechanism-and-bioassay-studies
#18
Wei-Yuan Wang, Xiu-Fen Zhao, Xiao-Han Ju, Ping Liu, Jing Li, Ya-Wen Tang, Shu-Ping Li, Xiao-Dong Li, Fu-Gui Song
Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm...
January 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29341317/apoptosis-induction-in-k562-human-myelogenous-leukaemia-cells-is-connected-to-the-modulation-of-wnt-%C3%AE-catenin-signalling-by-bhx-a-novel-pyrazoline-derivative
#19
Hanmei Bao, Qing Zhang, Yibo Du, Cai Zhang, Hui Xu, Zhongling Zhu, Zhao Yan
OBJECTIVES: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed...
January 16, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29340085/6-methylsulfonyl-hexyl-isothiocyanate-as-potential-chemopreventive-agent-molecular-and-cellular-profile-in-leukaemia-cell-lines
#20
Monia Lenzi, Veronica Cocchi, Marco Malaguti, Maria Cristina Barbalace, Silvia Marchionni, Silvana Hrelia, Patrizia Hrelia
Numerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of Wasabia Japonica, has stimulated the interest of researchers as a chemopreventive agent. In this particular study we have focused on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating activities, as well as its pro-apoptotic potential...
December 19, 2017: Oncotarget
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