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https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#1
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#2
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636919/monitoring-quantitative-ultrasound-parameter-changes-in-a-cell-pellet-model-of-cell-starvation
#3
Lauren A Wirtzfeld, Elizabeth S L Berndl, Gregory J Czarnota, Michael C Kolios
Although it has previously been shown that the spectral analysis of ultrasound backscatter data is sensitive to the cellular changes caused by apoptosis, the sensitivity of spectral analysis to oncosis or ischemic cell death had not previously been studied. Whereas many anticancer treatments induce apoptosis, others induce cell starvation, or oncosis. HT-29 colon adenocarcinoma cells were formed into pellets and covered in phosphate-buffered saline at room temperature for 56 h. The pellets were imaged every 8 h with high-frequency (55 MHz) ultrasound and the raw radio-frequency data processed...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636781/discovery-of-two-bombinin-peptides-with-antimicrobial-and-anticancer-activities-from-the-skin-secretion-of-oriental-fire-bellied-toad-bombina-orientalis
#4
Chang Zhou, Zhengming Wang, Xin Peng, Yao Liu, Yangjun Lin, Zhe Zhang, Yuling Qiu, Meihua Jin, Ran Wang, Dexin Kong
Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Bombinins are a group of amphibian derived peptides with broad spectrum antimicrobial activities that have been only identified from the ancient toad species, Bombina. In this study, we described the identification and characterization of a novel bombinin precursor which encoded a bombinin like peptide (BLP-7) and a novel bombinin H type peptide (named as Bombinin H-BO) from the skin secretion of Oriental fire-bellied toad, Bombina orientalis...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636454/anticancer-potential-of-sanguinarine-for-various-human-malignancies
#5
Iman W Achkar, Fatima Mraiche, Ramzi M Mohammad, Shahab Uddin
Sanguinarine (Sang) - a benzophenanthridine alkaloid extracted from Sanguinaria canadensis - exhibits antioxidant, anti-inflammatory, proapoptotic and growth inhibitory activities on tumor cells of various cancer types as established by in vivo and in vitro studies. Although the underlying mechanism of Sang antitumor activity is yet to be fully elucidated, Sang has displayed multiple biological effects, which remain to suggest its possible use in plant-derived treatments of human malignancies. This review covers the anticancer abilities of Sang including inhibition of aberrantly activated signal transduction pathways, induction of cell death and inhibition of cancer cell proliferation...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28636400/click-biotinylation-of-plga-template-for-biotin-receptor-oriented-delivery-of-doxorubicin-hydrochloride-in-4t1-cell-induced-breast-cancer
#6
Yuvraj Singh, K K Durga Rao Viswanadham, Arun Kumar Jajoriya, Jayagopal Meher, Kavit Raval, Swati Jaiswal, Jayant Dewangan, H K Bora, Srikanta Kumar Rath, Jawahar Lal, Durga Prasad Mishra, Manish Kumar Chourasia
PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (Biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing ammonium chloride in the external phase to constrain DOX in dissolved polymer phase by supressing its inherent aqueous solubility as per common ion effect...
June 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28636149/photocatalytic-interaction-of-aminophylline-riboflavin-leads-to-ros-mediated-dna-damage-and-cell-death-a-novel-phototherapeutic-mechanism-for-cancer
#7
Saniyya Khan, Imrana Naseem
The accompanied tissue devastation and systemic toxicity of chemotherapy has shifted the quest for having an effective and palliative cancer therapy towards photodynamic therapy (PDT). Riboflavin (Rf), an essential micronutrient is emerging as a potent tool of PDT, due to its excellent photosensitizing properties. It can be used as an efficient adjuvant for various anticancer drugs. The hemolytic and proteolytic effect of photoilluminated aminophylline (Am), a xanthine derivative, and Rf is well documented in literature...
June 21, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#8
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28634655/effect-of-adherence-on-pharmacokinetic-pharmacodynamic-relationships-of-oral-targeted-anticancer-drugs
#9
Evelina Cardoso, Chantal Csajka, Marie P Schneider, Nicolas Widmer
The emergence of oral targeted anticancer agents transformed several cancers into chronic conditions with a need for long-term oral treatment. Although cancer is a life-threatening condition, oncology medication adherence-the extent to which a patient follows the drug regimen that is intended by the prescriber-can be suboptimal in the long term, as in any other chronic disease. Poor adherence can impact negatively on clinical outcomes, notably because most of these drugs are given as a standard non-individualized dosage despite marked inter-individual variabilities that can lead to toxic or inefficacious drug concentrations...
June 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28634498/evaluation-of-in-vitro-cytotoxicity-biocompatibility-and-changes-in-the-expression-of-apoptosis-regulatory-proteins-induced-by-cerium-oxide-nanocrystals
#10
Shahanavaj Khan, Anees A Ansari, Christian Rolfo, Andreia Coelho, Maha Abdulla, Khayal Al-Khayal, Rehan Ahmad
Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed...
2017: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/28634389/novel-indolyl-chalcone-derivatives-inhibit-a549-lung-cancer-cell-growth-through-activating-nrf-2-ho-1-and-inducing-apoptosis-in-vitro-and-in-vivo
#11
Xuan Zhao, WenLiang Dong, YuanDi Gao, Dong-Shoo Shin, Qing Ye, Le Su, Fan Jiang, BaoXiang Zhao, JunYing Miao
Increasing evidence indicates that Nrf-2, named the nuclear factor-erythroid 2-related factor, may perform anticancer function. In this study, a series of novel substituted phenyl- (3-methyl-1H-indol-2-yl)-prop-2-en-1-one (indolyl-chalcone) derivatives were synthesized and their effects on Nrf-2 activity were observed. We found that compounds 3a-3d and 6c elevated Nrf-2 activity. Then we evaluated their anticancer activities in vitro and in vivo by utilizing human lung cancer cell line A549. The in vitro results showed that among the compounds, 3d performed effectively anti-growth activity by inducing A549 lung cancer cell apoptosis and activating Nrf-2/HO-1 (heme oxygenase-1) pathway...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633895/synthesis-of-meon-neoglycosides-of-digoxigenin-with-6-deoxy-and-2-6-dideoxy-d-glucose-derivatives-and-their-anticancer-activity
#12
Dong-Dong Wang, Xiao-San Li, Yu-Zhou Bao, Jie Liu, Xiao-Kun Zhang, Xin-Sheng Yao, Xue-Long Sun, Jin-Shan Tang
Cardiac glycosides show anticancer activities and their deoxy-sugar chains are vital for their anticancer effects. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and get more potent anticancer agents, a series of MeON-neoglycosides of digoxigenin was synthesized and evaluated. First, ten 6-deoxy- and 2,6-dideoxy-d-glucopyranosyl donors were synthesized starting from methyl α-d-glucopyranoside and 2-deoxy-d-glucose. Meanwhile, the digoxigenin was obtained by acidic hydrolysis of commercially available digoxin as glycosyl acceptor...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28631808/fabrication-of-%C3%AE-cyclodextrin-mediated-single-bimolecular-inclusion-complex-characterization-molecular-docking-in-vitro-release-and-bioavailability-studies-for-gefitinib-and-simvastatin-conjugate
#13
Souvik Basak, Sandip Mondal, Suddhasattya Dey, Plaban Bhattacharya, Achintya Saha, Vinay Deep Punetha, Ali Abbas, Nanda Gopal Sahoo
OBJECTIVES: Introduction of multiple molecules in a single inclusion complex, albeit cheaper, lacks conclusive attempts in earlier drug delivery reports. This manuscript emphasizes simultaneous incorporation of two anticancer drugs, gefitinib (G) and simvastatin (S), in a single molecule of β-cyclodextrin for the first time to achieve effective drug delivery. METHODS: The inclusion complex (GSBCD) was prepared by cosolvent evaporation technique using β-cyclodextrin (BCD) as carrier...
June 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28631564/indole-3-carbinol-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-through-suppression-of-stat5-and-akt-signaling-pathways
#14
Majid Safa, Leila Jafari, Fatemeh Alikarami, Rima Manafi Shabestari, Ahmad Kazemi
Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, idenication of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631560/mithramycin-inhibits-epithelial-to-mesenchymal-transition-and-invasion-by-downregulating-sp1-and-snai1-in-salivary-adenoid-cystic-carcinoma
#15
Jiasu Li, Hongmei Gao, Lingxu Meng, Lin Yin
Mithramycin exhibits certain anticancer effects in glioma, metastatic cerebral carcinoma, malignant lymphoma, chorionic carcinoma and breast cancer. However, its effects on salivary adenoid cystic carcinoma remain unclear. Here, we report that mithramycin significantly inhibited epithelial-to-mesenchymal transition and invasion in human salivary adenoid cystic carcinoma cell lines. The underlying mechanism for this activity was further demonstrated to involve decreasing the expression of the transcription factors specificity protein 1 and SNAI1...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631252/synthesis-and-characterization-of-novel-carboxymethyl-assam-bora-rice-starch-for-the-controlled-release-of-cationic-anticancer-drug-based-on-electrostatic-interactions
#16
Sharmistha Mohapatra, Anees Ahmad Siddiqui, Mohammed Anwar, Neha Bhardwaj, Sohail Akhter, Farhan Jalees Ahmad
Carboxymethyl Assam Bora rice starch (CM-ABRS) was chemically synthesized in non-aqueous medium with the optimum degree of substitution (DS) of 1.23, and physicochemically characterized by FT-IR, DSC, XRD, and SEM analysis. Comparative evaluation of CM-ABRS with native starch (ABRS) for powder flow characteristics, swelling index, apparent solubility, rheological properties, textural properties, and mucoadhesive studies were carried out. The aim of the current work was to investigate the potential of CM-ABRS as a novel carrier for the water-soluble chemotherapeutic, doxorubicin hydrochloride (DOX)...
June 19, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28631153/lung-cancer-in-the-oldest-old-a-nation-wide-study-in-the-netherlands
#17
Karlijn J G Schulkes, Carin A M Pouw, Elisabeth J M Driessen, Leontine J R van Elden, Frederiek van den Bos, Maryska L G Janssen-Heijnen, Jan-Willem J Lammers, Marije E Hamaker
INTRODUCTION: An important step in improving research and care for the oldest patients with lung cancer is analyzing current data regarding diagnostic work-up, treatment choices, and survival. METHODS: We analyzed data on lung cancer from the Netherlands Cancer Registry (NCR-IKNL) regarding diagnostic work-up, treatment, and survival in different age categories; the oldest old (≥85 years of age) versus those aged 71-84 (elderly) and those aged ≤70 years (younger patients)...
June 19, 2017: Lung
https://www.readbyqxmd.com/read/28631098/urolithins-impair-cell-proliferation-arrest-the-cell-cycle-and-induce-apoptosis-in-umuc3-bladder-cancer-cells
#18
Joana Liberal, Anália Carmo, Célia Gomes, Maria Teresa Cruz, Maria Teresa Batista
Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28631095/decorin-gene-upregulation-mediated-by-an-adeno-associated-virus-vector-increases-intratumoral-uptake-of-nab-paclitaxel-in-neuroblastoma-via-inhibition-of-stabilin-1
#19
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu
The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28630044/single-molecule-fret-analysis-discloses-the-dynamics-of-the-dna-topoisomerase-ii-top2-interaction-in-the-presence-of-top2-targeting-agents
#20
Wan-Chen Huang, Chun-Ying Lee, Tao-Shih Hsieh
Topoisomerases play crucial roles in DNA replication, transcription, and recombination. For instance, topoisomerase II (Top2) is critically important for resolving DNA tangles during cell division, and as such, it is a broad anticancer drug target. Top2 regulates DNA topology by transiently breaking one double stranded DNA molecule (cleavage), allowing a second double strand to pass through the opened DNA gate (opening), and then closing the gate by rejoining the broken ends. Drugs that modulate Top2 catalysis may therefore affect enzymatic activity at several different steps...
June 19, 2017: Journal of Biological Chemistry
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