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https://read.qxmd.com/read/30785963/introduction-of-the-yte-mutation-into-the-non-immunogenic-hiv-bnab-pgt121-induces-anti-drug-antibodies-in-macaques
#1
Yvonne J Rosenberg, George K Lewis, David C Montefiori, Celia C LaBranche, Mark G Lewis, Lori A Urban, Jonathan P Lees, Lingjun Mao, Xiaoming Jiang
Recombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by the introduction of defined mutations in the crystallizable fragment (Fc) domains eg YTE (M252Y/S254T/T256E) and LS (M428L/N434S), as a consequence of increased half-lives and prolonged duration of protection. However, the functional properties of any biologic may be compromised by unanticipated immunogenicity in humans, rendering them ineffective...
2019: PloS One
https://read.qxmd.com/read/30785365/ruxolitinib-treatment-reduces-monocytic-superoxide-radical-formation-without-affecting-hydrogen-peroxide-formation-or-systemic-oxidative-nucleoside-damage-in-myelofibrosis
#2
Mads Emil Bjørn, Marie Klinge Brimnes, Sif Gudbrandsdottir, Christen Lykkegaard Andersen, Henrik Enghusen Poulsen, Trine Henriksen, Hans Carl Hasselbalch, Claus Henrik Nielsen
The role of excess reactive oxygen species (ROS) with consequent DNA/RNA damage is now recognized as a hallmark of cancer. In JAK2V617F mutated myeloproliferative neoplasms, ROS have been suggested to be important factors in disease initiation and progression. Ruxolitinib is the most widely used drug for myelofibrosis, because it improves symptom-score. However, both the anti-clonal potential and improvement in overall survival are limited. We investigated the impact of ruxolitinib on formation of superoxide radical and hydrogen peroxide by monocytes in sequentially acquired blood samples from patients with myelofibrosis...
February 20, 2019: Leukemia & Lymphoma
https://read.qxmd.com/read/30785086/mir-125b-suppresses-oral-oncogenicity-by-targeting-the-anti-oxidative-gene-prxl2a
#3
Yi-Fen Chen, Yun-Yen Wei, Cheng-Chieh Yang, Chung-Ji Liu, Li-Yin Yeh, Chung-Hsien Chou, Kuo-Wei Chang, Shu-Chun Lin
Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties...
February 13, 2019: Redox Biology
https://read.qxmd.com/read/30785037/chondroitin-sulfate-functionalized-polymeric-nanoparticles-for-colon-cancer-targeted-chemotherapy
#4
Menghang Zu, Lijun Ma, Xueqing Zhang, Dengchao Xie, Yuejun Kang, Bo Xiao
Targeted delivery of chemotherapeutic drugs to tumors is a major challenge in colon cancer chemotherapy. To overcome this bottleneck, we loaded camptothecin (CPT) into polymeric nanoparticles (NPs), and further functionalized their surface with chondroitin sulfate (CS). The resulting CS-CPT-NPs had a desirable hydrodynamic diameter (289 nm), narrow particle size distribution (polydispersity index = 0.192) and neutral surface charge. Furthermore, in vitro experiments revealed that the surface functionalization of CS endowed NPs with the capacity of colon cancer-targeted drug delivery, and significantly improved the anti-colon cancer activities and pro-apoptosis effects against colon cancer cells...
February 16, 2019: Colloids and Surfaces. B, Biointerfaces
https://read.qxmd.com/read/30784890/analysis-of-44-pharmaceuticals-consumed-by-elderly-using-liquid-chromatography-coupled-to-tandem-mass-spectrometry
#5
Cristian Gómez-Canela, Teresa Sala-Comorera, Víctor Pueyo, Carlos Barata, Silvia Lacorte
Elderly people represent about the 15% of the total world population and often include a polymedicated age group with an average consumption of 5-10 pills per day. The main pharmaceuticals consumed are antianalgesics, antidiabetics, anti-parkinson compounds, anti-convulsants, drugs to treat constipation and drugs to treat cancer. In this study, we have developed a multiresidue method for the analysis of 44 selected pharmaceuticals prioritized according to the foremost consumption by the elderly in effluents from senior residences...
February 13, 2019: Journal of Pharmaceutical and Biomedical Analysis
https://read.qxmd.com/read/30784875/new-nsaid-pt-iv-prodrugs-to-suppress-metastasis-and-invasion-of-tumor-cells-and-enhance-anti-tumor-effect-in-vitro-and-in-vivo
#6
Xue-Qing Song, Zhong-Ying Ma, Yi-Gang Wu, Miao-Liang Dai, Dong-Bo Wang, Jing-Yuan Xu, Yangzhong Liu
The great interest in epithelial-to-mesenchymal transition (EMT) programme lies in its association with process of metastasis and invasion, which is a crucial cause of cancer-related death. Herein, we designed and reported three new NSAID-Pt(IV) prodrugs, taking Non-Steroid Anti-Inflammatory Drugs (NSAIDs) to disrupt EMT programme and assist genotoxic platinum-based drugs as a cytotoxicity booster, to offer a class of potential anticarcinogens with a multi-functional action mechanism. The NSAID-Pt(IV) prodrugs, especially Eto-Pt(IV), highly enhanced cellular uptake with amount up to 42-fold at 3 h compared with CDDP, and greatly increased DNA damage and cell apoptosis, showing much higher cytotoxicity than cisplatin in the tested cancer cells even in A549/cis cells...
February 13, 2019: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30784282/ambra1-inhibits-paclitaxel-induced-apoptosis-in-breast-cancer-cells-by-modulating-the-bim-mitochondrial-pathway
#7
Wei-Liang Sun, Li Wang, Jie Luo, Hua-Wei Zhu, Zheng-Wen Cai
Cancer cells often evade apoptosis induced by anti-cancer drugs, which reduces the efficacy of the drugs. Autophagy/Beclin 1 regulator 1 (Ambra1) is a crucial proautophagic protein. It also plays an important role in the execution of apoptosis. However, the mechanism by which Ambra1 regulates apoptosis has not been fully clarified. Moreover, whether Ambra1 participates in the regulation of paclitaxel-induced apoptosis in breast cancer cells is not clear. Here, we show that Ambra1 inhibits paclitaxel-induced apoptosis in breast cancer cells...
February 20, 2019: Neoplasma
https://read.qxmd.com/read/30784027/immune-checkpoint-inhibitors-and-beyond-an-overview-of-immune-based-therapies-in-merkel-cell-carcinoma
#8
REVIEW
Mahtab Samimi
Merkel cell carcinoma (MCC) is an aggressive skin cancer. Until 2017, patients with advanced disease were typically treated with conventional chemotherapies, with a median response duration of 3 months. Increased evidence of the role of the immune system in controlling this cancer has paved the way for immune-based therapies, with programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitors at the frontline. Avelumab, an anti-PD-L1 antibody, was the first-ever drug approved in advanced MCC after showing meaningful efficacy in a second-line setting...
February 19, 2019: American Journal of Clinical Dermatology
https://read.qxmd.com/read/30783518/targeted-human-cytolytic-fusion-proteins-at-the-cutting-edge-harnessing-the-apoptosis-inducing-properties-of-human-enzymes-for-the-selective-elimination-of-tumor-cells
#9
REVIEW
Neelakshi Mungra, Sandra Jordaan, Precious Hlongwane, Krupa Naran, Shivan Chetty, Stefan Barth
Patient-specific targeted therapy represents the holy grail of anti-cancer therapeutics, allowing potent tumor depletion without detrimental off-target toxicities. Disease-specific monoclonal antibodies have been employed to bind to oncogenic cell-surface receptors, representing the earliest form of immunotherapy. Targeted drug delivery was first achieved by means of antibody-drug conjugates, which exploit the differential expression of tumor-associated antigens as a guiding mechanism for the specific delivery of chemically-conjugated chemotherapeutic agents to diseased target cells...
January 25, 2019: Oncotarget
https://read.qxmd.com/read/30783515/enhanced-phosphatidylserine-selective-cancer-therapy-with-irradiation-and-sapc-dops-nanovesicles
#10
Harold W Davis, Subrahmanya D Vallabhapurapu, Zhengtao Chu, Swarajya L Vallabhapurapu, Robert S Franco, Michelle Mierzwa, William Kassing, William L Barrett, Xiaoyang Qi
Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner...
January 25, 2019: Oncotarget
https://read.qxmd.com/read/30783443/epigallocatechin-gallate-inhibits-cell-growth-and-regulates-mirna-expression-in-cervical-carcinoma-cell-lines-infected-with-different-high-risk-human-papillomavirus-subtypes
#11
Yu Zhu, Yongfang Huang, Mingmin Liu, Qi Yan, Wanhong Zhao, Ping Yang, Qin Gao, Juanjuan Wei, Wenxia Zhao, Lishan Ma
The aim of the present study was to investigate the inhibitory effects of the polyphenol epigallocatechin-3-gallate (EGCG) on the growth of cervical carcinoma cell lines infected with different high-risk human papillomavirus (HPV) subtypes, as well as the associated regulation of microRNA (miR) expression. Cell proliferation was measured using an MTT assay. The effects of 7 different concentrations of EGCG (100, 80, 60, 40, 20, 10 and 0 µg/ml) on HeLa cell proliferation were assessed. HeLa cell growth was significantly inhibited by EGCG in a dose- and time-dependent manner (P<0...
March 2019: Experimental and Therapeutic Medicine
https://read.qxmd.com/read/30783079/dihydroartemisinin-inhibits-prostate-cancer-via-jarid2-mir-7-mir-34a-dependent-downregulation-of-axl
#12
Juliano D Paccez, Kristal Duncan, Durairaj Sekar, Ricardo G Correa, Yihong Wang, Xuesong Gu, Manoj Bashin, Kelly Chibale, Towia A Libermann, Luiz F Zerbini
Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells. Dihydroartemisinin treatment synergizes with docetaxel, a standard of care in metastatic prostate cancer increasing overall survival of mice with human xenografts...
February 19, 2019: Oncogenesis
https://read.qxmd.com/read/30782852/organic-anion-transporting-polypeptides-emerging-roles-in-cancer-pharmacology
#13
Rachael R Schulte, Richard H Ho
The organic anion transporting polypeptides (OATPs) are a superfamily of drug transporters involved in the uptake and disposition of a wide array of structurally divergent endogenous and exogenous substrates, including steroid hormones, bile acids, and commonly used drugs, such as anti-infectives, anti-hypertensives, and cholesterol lowering agents. In the past decade, OATPs, primarily OATP1A2, OATP1B1, and OATP1B3, have emerged as potential mediators of chemotherapy disposition, including drugs such as methotrexate, doxorubicin, paclitaxel, docetaxel, irinotecan and its important metabolite SN-38, and certain tyrosine kinase inhibitors...
February 19, 2019: Molecular Pharmacology
https://read.qxmd.com/read/30782785/the-selective-hdac6-inhibitor-nexturastat-a-induces-apoptosis-overcomes-drug-resistance-and-inhibits-tumor-growth-in-multiple-myeloma
#14
Xiaoyang Sun, Yu Xie, Xiaoshen Sun, Yao Yao, Hujun Li, Zhenyu Li, Ruosi Yao, Kailin Xu
Multiple myeloma (MM) is a hematological malignancy of plasma cells that produce a monoclonal immunoglobulin protein. Despite significant advances in the treatment of MM, challenges such as resistance to therapy remain. Currently, inhibition of histone deacetylases (HDACs) is emerging as a potential method for treating cancers. Numerous HDAC inhibitors are being studied for use in monotherapy or in conjunction with other agents for MM. In this study, we investigated the anti-myeloma effect of Nexturastat A (NexA), a novel selective HDAC6 inhibitor...
February 19, 2019: Bioscience Reports
https://read.qxmd.com/read/30782296/exploration-of-pro-apoptotic-effect-of-thymoquinone-on-oral-squamous-cell-carcinoma-cells-through-pi3k-akt-signaling-pathway
#15
Xun Ren, Wei Luo
Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer type in the world, with a 5-year survival rate of only 40% to 50%. Finding effective anti-tumor drug candidates is quite necessary for the progression of OSCC therapy. In this study, the role of Thymoquinone (TQ) in OSCC cells was studied. It was confirmed that TQ can inhibit the proliferation, migration and invasion of KB cells, and can also achieve apoptosis by inhibiting the activation of PI3K/Akt pathway. Therefore, TQ is an effective candidate for the treatment of OSCC...
January 31, 2019: Cellular and Molecular Biology
https://read.qxmd.com/read/30782163/late-onset-isolated-adrenocorticotropic-hormone-deficiency-caused-by-nivolumab-a-case-report
#16
Ayumu Takeno, Masahiro Yamamoto, Miwa Morita, Sayuri Tanaka, Ippei Kanazawa, Mika Yamauchi, Sakae Kaneko, Toshitsugu Sugimoto
BACKGROUND: Immune checkpoint inhibitors including nivolumab, an anti-programmed cell death protein 1 antibody, are recently developed cancer immunotherapy agents. Immune checkpoint inhibitors are known to cause autoimmune-related side effects including endocrine dysfunctions. However, there are few reports on late-onset isolated adrenocorticotropic hormone (ACTH) deficiency caused by nivolumab. CASE PRESENTATION: The patient was a 72-year-old female. When she was 64 years old, she was diagnosed with malignant melanoma of the left thigh accompanied by left inguinal lymph node metastases, and she received several courses of chemotherapy for malignant melanoma followed by the resection of these lesions...
February 19, 2019: BMC Endocrine Disorders
https://read.qxmd.com/read/30781885/therapeutic-approaches-of-resveratrol-on-endometriosis-via-anti-inflammatory-and-anti-angiogenic-pathways
#17
REVIEW
Ana-Maria Dull, Marius Alexandru Moga, Oana Gabriela Dimienescu, Gabriela Sechel, Victoria Burtea, Costin Vlad Anastasiu
Endometriosis represents a severe gynecological pathology, defined by implantation of endometrial glands and stroma outside the uterine cavity. This pathology affects almost 15% of women during reproductive age and has a wide range of consequences. In affected women, infertility has a 30% rate of prevalence and endometriosis implants increase the risk of ovarian cancer. Despite long periods of studies and investigations, the etiology and pathogenesis of this disease still remain not fully understood. Initially, endometriosis was related to retrograde menstruation, but new theories have been launched, suggesting that chronic inflammation can influence the development of endometriosis because inflammatory mediators have been identified elevated in patients with endometriosis, specifically in the peritoneal fluid...
February 13, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/30781804/cytotoxic-activity-of-the-histone-deacetylase-3-selective-inhibitor-pojamide-on-mda-mb-231-triple-negative-breast-cancer-cells
#18
Claudio Luparello, Dalia Maria Lucia Asaro, Ilenia Cruciata, Storm Hassell-Hart, Supojjanee Sansook, John Spencer, Fabio Caradonna
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide ( N ¹-(2-aminophenyl)- N ⁸-ferrocenyloctanediamide) and its two derivatives N ¹-(2-aminophenyl)- N ⁶-ferrocenyladipamide and N ¹-(2-aminophenyl)- N ⁸-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 μM concentration caused an approximate halving of cell number after 24 h of exposure, whereas the tetrafluoroborate derivative exerted no effect on cell survival nor proliferation...
February 13, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30781783/garcinol-sensitizes-nsclc-cells-to-standard-therapies-by-regulating-emt-modulating-mirnas
#19
Mohd Farhan, Arshi Malik, Mohammad Fahad Ullah, Sarah Afaq, Mohd Faisal, Ammad Ahmad Farooqi, Bernhard Biersack, Rainer Schobert, Aamir Ahmad
Garcinol, a dietary factor obtained from Garcinia indica , modulates several key cellular signaling pathways as well as the expression of miRNAs. Acquired resistance to standard therapies, such as erlotinib and cisplatin, is a hallmark of non-small cell lung cancer (NSCLC) cells that often involves miRNA-regulated epithelial-to-mesenchymal transition (EMT). We used A549 cells that were exposed to transforming growth factor beta 1 (TGF-β1), resulting in A549M cells with mesenchymal and drug resistant phenotype, and report that garcinol sensitized resistant cells with mesenchymal phenotype to erlotinib as well as cisplatin with significant decrease in their IC50 values...
February 13, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30781512/shedding-light-on-the-interaction-of-human-anti-apoptotic-bcl-2-protein-with-ligands-through-biophysical-and-in-silico-studies
#20
Joao Ramos, Jayaraman Muthukumaran, Filipe Freire, João Paquete-Ferreira, Ana Rita Otrelo-Cardoso, Dmitri Svergun, Alejandro Panjkovich, Teresa Santos-Silva
Bcl-2 protein is involved in cell apoptosis and is considered an interesting target for anti-cancer therapy. The present study aims to understand the stability and conformational changes of Bcl-2 upon interaction with the inhibitor venetoclax, and to explore other drug-target regions. We combined biophysical and in silico approaches to understand the mechanism of ligand binding to Bcl-2. Thermal shift assay (TSA) and urea electrophoresis showed a significant increase in protein stability upon venetoclax incubation, which is corroborated by molecular docking and molecular dynamics simulations...
February 16, 2019: International Journal of Molecular Sciences
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