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https://www.readbyqxmd.com/read/28738540/regulatory-players-of-dna-damage-repair-mechanisms-role-in-cancer-chemoresistance
#1
REVIEW
Kunnathur Murugesan Sakthivel, Sreedharan Hariharan
DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738532/genipin-attenuates-cisplatin-induced-nephrotoxicity-by-counteracting-oxidative-stress-inflammation-and-apoptosis
#2
Eglal Mahgoub, Shanmugam Muthu Kumaraswamy, Kamal Hassan Kader, Balaji Venkataraman, Shreesh Ojha, Ernest Adeghate, Mohanraj Rajesh
Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28737825/combination-of-rapamycin-and-garlic-derived-s-allylmercaptocysteine-induces-colon-cancer-cell-apoptosis-and-suppresses-tumor-growth-in-xenograft-nude-mice-through-autophagy-p62-nrf2-pathway
#3
Siying Li, Guang Yang, Xiaosong Zhu, Lin Cheng, Yueyue Sun, Zhongxi Zhao
The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice...
July 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28736641/bone-marrow-tolerance-during-postoperative-chemotherapy-in-colorectal-carcinomas
#4
Neil B Newman, Rebecca A Moss, Nell Maloney-Patel, Kristen Donohue, Teresa V Brown, Michael J Nissenblatt, Shou-En Lu, Salma K Jabbour
BACKGROUND: This study seeks to quantify and compare bone marrow tolerance during postoperative chemotherapy therapy between rectal cancer vs. colon cancer patients. During rectal cancer treatment, patients receive neoadjuvant chemoradiation (CRT) irradiation which can exacerbate the hematologic toxicity (HT) via incidental irradiation of the pelvic bone marrow (PBM) during myelosuppressive postoperative chemotherapy. In contrast, colon cancer patients receive the same postoperative myelosuppressive chemotherapy but do not routinely receive preoperative chemoradiation therapy...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28735162/tumor-infiltrating-lymphocytes-in-breast-cancer-according-to-tumor-subtype-current-state-of-the-art
#5
REVIEW
Cinzia Solinas, Luisa Carbognin, Pushpamali De Silva, Carmen Criscitiello, Matteo Lambertini
The recent success of the immune checkpoint blockade in cancer immunotherapy has modified the treatment algorithms in a variety of aggressive neoplastic diseases. Nevertheless, optimal selection of ideal candidates to these drugs remains a challenge. The presence, location and composition of a pre-existing tumor immune infiltrate seem to impact on the benefit from these treatments. The association between the presence of baseline tumor-infiltrating lymphocytes (TIL) and patients' outcomes has been widely investigated in breast cancer, although immunotherapeutic strategies have historically been less successful with respect to other neoplastic diseases such as melanoma and kidney cancer...
July 20, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28735070/suppression-of-the-atp-binding-cassette-transporter-abcc4-impairs-neuroblastoma-tumour-growth-and-sensitises-to-irinotecan-in%C3%A2-vivo
#6
Jayne Murray, Emanuele Valli, Denise M T Yu, Alan M Truong, Andrew J Gifford, Georgina L Eden, Laura D Gamble, Kimberley M Hanssen, Claudia L Flemming, Alvin Tan, Amanda Tivnan, Sophie Allan, Federica Saletta, Leanna Cheung, Michelle Ruhle, John D Schuetz, Michelle J Henderson, Jennifer A Byrne, Murray D Norris, Michelle Haber, Jamie I Fletcher
The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28735042/improved-selectivity-and-cytotoxic-effects-of-irinotecan-via-liposomal-delivery-a-comparative-study-on-hs68-and-hela-cells
#7
Ana Casadó, Margarita Mora, M Lluïsa Sagristá, Santi Rello-Varona, Pilar Acedo, Juan Carlos Stockert, Magdalena Cañete, Angeles Villanueva
Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion...
July 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28734960/pharmacokinetic-interactions-of-curcuminoids-with-conventional-drugs-a-review
#8
REVIEW
Roodabeh Bahramsoltani, Roja Rahimi, Mohammad Hosein Farzaei
ETHNOPHARMACOLOGICAL RELEVANCE: Herb-drug interactions are of great concern in health practices. Curcumin is a natural polyphenol extracted from turmeric, a spice widely used all over the world. Curcumin is clinically used due to its acceptable safety profile and therapeutic efficacy. AIM OF THE STUDY: Current paper aims to highlight the effect of curcumin on concomitantly used drugs. METHODS: Electronic databases including PubMed, Scopus and Science Direct were searched with the keywords "curcumin" in the title/abstract and "drug interaction," "drug metabolism," "cytochrome," "P-glycoprotein" and "P450" in the whole text...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28734166/naturally-occurring-immunomodulators-with-antitumor-activity-an-insight-on-their-mechanisms-of-action
#9
REVIEW
Shimaa Ibrahim Abdelmonym Mohamed, Ibrahim Jantan, Md Areeful Haque
Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities...
July 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28733879/anticancer-activity-of-salicin-and-fenofibrate
#10
Marwa Sabaa, Hassan M ELFayoumi, Shimaa Elshazly, Mahmoud Youns, Waleed Barakat
Cancer refers to a disorder of cell proliferation that leads to tumor production. Cancer is usually treated by surgery, chemotherapeutic drugs, and radiation. Despite the presence of many anticancer drugs, cancer is still an uncontrolled disease and is a major cause of death worldwide. In addition, most anticancer drugs have severe side effects that can limit their use in some patients. This study aims to investigate the possible anticancer activity of two clinically used drugs: a natural antioxidant agent (salicin) and an antihyperlipidemic agent (fenofibrate) against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (Panc-1)...
July 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28733703/induction-of-accelerated-senescence-by-the-microtubule-stabilizing-agent-peloruside-a
#11
Ariane Chan, Connie Gilfillan, Nikki Templeton, Ian Paterson, Peter T Northcote, John H Miller
Chemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7...
July 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733622/tumor-targeted-delivery-of-sirna-using-fatty-acyl-cgkrk-peptide-conjugates
#12
Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Kumar Tiwari, Hamidreza Montazeri Aliabadi
Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#13
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732326/therapeutic-applications-of-histone-deacetylase-inhibitors-in-sarcoma
#14
REVIEW
Fan Tang, Edwin Choy, Chongqi Tu, Francis Hornicek, Zhenfeng Duan
Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28731328/bisphosphonate-functionalized-hydroxyapatite-nanoparticles-for-the-delivery-of-the-bromodomain-inhibitor-jq1-in-the-treatment-of-osteosarcoma
#15
Victoria Wu, Jarrett Mickens, Vuk Uskokovic
Osteosarcoma (OS) is one of the most common neoplasia among children and its survival statistics have been stagnating since the combinatorial anticancer therapy triad was first introduced. Here we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Both additives decreased the crystallinity of HAp, but the effect was more intense for medronate because of its higher affinity for HAp...
July 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28731262/nephroprotective-effects-of-anthocyanin-from-the-fruits-of-panax-ginseng-gfa-on-cisplatin-induced-acute-kidney-injury-in-mice
#16
Zhen-Lan Qi, Zi Wang, Wei Li, Jin-Gang Hou, Ying Liu, Xin-Dian Li, Hui-Ping Li, Ying-Ping Wang
Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin...
July 21, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28730788/topoisomerase-i-deregulation-in-laryngeal-squamous-cell-carcinomas-based-on-tissue-microarray-analysis
#17
Theodoros A Papadas, Evangelos Tsiambas, Nicholas S Mastronikolis, Andreas Karameris, Stylianos N Mastronikolis, Athanasios T Papadas, Panagiotis P Fotiades, Vasileios Ragos
PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan)...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729866/cytokine-induced-killer-cells-as-pharmacological-tools-for-cancer-immunotherapy
#18
REVIEW
Xingchun Gao, Yajing Mi, Na Guo, Hao Xu, Lixian Xu, Xingchun Gou, Weilin Jin
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3(+)CD56(+) natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28729229/pharbitis-nil-pn-induces-apoptosis-and-autophagy-in-lung-cancer-cells-and-autophagy-inhibition-enhances-pn-induced-apoptosis
#19
Hyun Jin Jung, Ju-Hee Kang, Seungho Choi, Youn Kyoung Son, Kang Ro Lee, Je Kyung Seong, Sun Yeou Kim, Seung Hyun Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Pharbitis Nil (PN) is used as a main component of the existing drug, DA-9701, which was developed to treat functional dyspepsia (FD) in Korea. PN extracts isolated from its seeds have been reported to have anticancer effects. AIM OF THE STUDY: The purpose of this study was to investigate the underlying mechanism of the chemotherapeutic effects of PN in lung cancer cells. MATERIALS AND METHODS: We performed MTT assays, colony formation assays, flow cytometry assays, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence analysis, and cell counting assays to study the molecular mechanism of chemotherapeutic effects of PN in lung cancer cells...
July 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28728976/effect-of-alkylaminophenols-on-growth-inhibition-and-apoptosis-of-bone-cancer-cells
#20
Phuong Doan, Tien Nguyen, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu
In this work, we report the anticancer properties of a series of 11 chemically synthesized alkylaminophenols against human osteosarcoma U2OS tumor cell line. Several assays including cytotoxicity, inhibitor kinetic study, cell migration, Annexin-V/PI double staining, reactive oxygen species (ROS) and caspase 3/7 assays were conducted on this cell line. Cytotoxic 2-((3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol was determined to have an IC50 value of 36.6μM against U2OS cells and it also inhibits the cell growth in time-dependent manner...
July 17, 2017: European Journal of Pharmaceutical Sciences
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