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https://www.readbyqxmd.com/read/29786944/design-synthesis-and-evaluation-of-a-novel-series-of-inhibitors-reversing-p-glycoprotein-mediated-multidrug-resistance
#1
Hesham Ghaleb, Huilan Li, Mutta Kairuki, Qianqian Qiu, Xinzhou Bi, Chunxia Liu, Chen Liao, Jieming Li, Kamal Hezam, Wenlong Huang, Hai Qian
Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR-reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells...
May 22, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29786894/the-prognostic-role-of-phase-angle-in-advanced-cancer-patients-a-systematic-review
#2
REVIEW
Mayane Marinho Esteves Pereira, Mariana Dos Santos Campello Queiroz, Nathália Masiero Cavalcanti de Albuquerque, Juliana Rodrigues, Emanuelly Varea Maria Wiegert, Larissa Calixto-Lima, Livia Costa de Oliveira
Phase angle (PA) is a ratio between the reactance and resistance obtained by bioelectric impedance analysis and has been interpreted as a cell membrane integrity indicator and a predictor of total body cell mass. A low PA may suggest deterioration of the cell membrane, which in advanced cancer patients may result in a reduced overall survival (OS). This systematic review sought to investigate the current evidence regarding whether there is an association between PA and OS in patients with advanced cancer (ie, metastatic disease)...
May 22, 2018: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/29786792/protocols-for-the-study-of-taxanes-chemosensitivity-in-prostate-cancer
#3
M Luz Flores, Carmen Sáez
Prostate cancer is major cause of cancer-related death among men in Western countries. Locally advanced prostate cancers are treated with castration therapy, which is initially effective, but after months the disease progresses to a hormone-refractory state whose treatment is chemotherapy based on taxanes. Although taxanes improve the survival of patients with castration-resistant prostate cancers, these patients often develop chemotherapy resistance, and new therapeutic strategies are necessary. Taxanes exert their action through interaction with β-tubulin which triggers cell cycle arrest in mitosis and the subsequent induction of the intrinsic apoptotic pathway...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786787/protocols-for-migration-and-invasion-studies-in-prostate-cancer
#4
Arjanneke F van de Merbel, Geertje van der Horst, Jeroen T Buijs, Gabri van der Pluijm
Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786782/preclinical-impact-of-high-dose-intermittent-antiangiogenic-tyrosine-kinase-inhibitor-pazopanib-in-intrinsically-resistant-tumor-models
#5
Elaine Reguera-Nuñez, Shan Man, Ping Xu, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29786670/deubiquitinylase-usp47-promotes-rela-phosphorylation-and-survival-in-gastric-cancer-cells
#6
Lara Naghavi, Martin Schwalbe, Ahmed Ghanem, Michael Naumann
Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required...
May 22, 2018: Biomedicines
https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#7
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29786108/mir%C3%A2-494-inhibits-cancer%C3%A2-initiating-cell-phenotypes-and-reverses-resistance-to-lapatinib-by-downregulating-fgfr2-in-her2%C3%A2-positive-gastric-cancer
#8
Yanxia Yu, Xuejuan Yu, Hong Liu, Qingxun Song, Yongmei Yang
In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP‑competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2‑positive gastric cancer. The aim of the present study was to explore the effects of miR‑494 and FGFR2 in regulation of cancer‑initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2‑positive gastric cancer...
May 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786077/tumor-derived-exosomes-promote-tumor-self-seeding-in-hepatocellular-carcinoma-by-transferring-mirna-25-5p-to-enhance-cell-motility
#9
Hao Liu, Wei Chen, Xiao Zhi, En-Jiang Chen, Tao Wei, Jian Zhang, Jian Shen, Li-Qiang Hu, Bin Zhao, Xin-Hua Feng, Xue-Li Bai, Ting-Bo Liang
Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#10
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786070/selective-elimination-of-senescent-cells-by-mitochondrial-targeting-is-regulated-by-ant2
#11
Sona Hubackova, Eliska Davidova, Katerina Rohlenova, Jan Stursa, Lukas Werner, Ladislav Andera, LanFeng Dong, Mikkel G Terp, Zdenek Hodny, Henrik J Ditzel, Jakub Rohlena, Jiri Neuzil
Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785875/egfr-tkis-in-non-small-cell-lung-cancer-focus-on-clinical-pharmacology-and-mechanisms-of-resistance
#12
Stefano Fogli, Beatrice Polini, Marzia Del Re, Iacopo Petrini, Antonio Passaro, Stefania Crucitta, Eleonora Rofi, Romano Danesi
The clinical introduction of EGFR-TKIs within the oncologic armamentarium has changed the therapeutic landscape of non-small-cell lung cancer (NSCLC) creating widespread expectations both in patients and clinicians. However, several gaps in current understanding leave open important questions regarding the use of these drugs in clinical practice. For instance, there is uncertainty in regard to which EGFR-TKI should be given first in naive patients with EGFR-driven malignancies since different generations of drugs are available with different pharmacological profiles...
May 22, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29785434/integration-of-phospholipid-hyaluronic-acid-methotrexate-nanocarrier-assembly-and-amphiphilic-drug-drug-conjugate-for-synergistic-targeted-delivery-and-combinational-tumor-therapy
#13
Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29785122/aloperine-executes-antitumor-effects-through-the-induction-of-apoptosis-and-cell-cycle-arrest-in-prostate-cancer-in-vitro-and-in-vivo
#14
Zhixin Ling, Han Guan, Zonghao You, Can Wang, Ling Hu, Lei Zhang, Yiduo Wang, Shuqiu Chen, Bin Xu, Ming Chen
Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785088/insight-into-resistance-mechanism-of-anaplastic-lymphoma-kinase-to-alectinib-and-jh-viii-157-02-caused-by-g1202r-solvent-front-mutation
#15
Han Wang, Yao Wang, Wentao Guo, Bin Du, Xiaobing Huang, Riping Wu, Baoyu Yang, Xiaoyan Lin, Yilan Wu
Background: Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29784926/clinical-utility-of-circulating-non-coding-rnas-an-update
#16
REVIEW
Simone Anfossi, Anna Babayan, Klaus Pantel, George A Calin
Over the past decade, the amount of research and the number of publications on associations between circulating small and long non-coding RNAs (ncRNAs) and cancer have grown exponentially. Particular focus has been placed on the development of diagnostic and prognostic biomarkers to enable efficient patient management - from early detection of cancer to monitoring for disease recurrence or progression after treatment. Owing to their high abundance and stability, circulating ncRNAs have potential utility as non-invasive, blood-based biomarkers that can provide information on tumour biology and the effects of treatments, such as targeted therapies and immunotherapies...
May 21, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#17
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784669/autophagy-cell-viability-and-chemo-resistance-are-regulated-by-mir-489-in-breast-cancer
#18
Hexin Chen, Mithil Soni, Yogin Patel, Eleni Markoutsa, Chunfa Jie, Shou Liu, Peisheng Xu
It is postulated that the complexity and heterogeneity in cancer may hinder most efforts that target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as microRNAs (miRs), holds promise for future cancer therapy. One such miR, miR-489, is downregulated in majority of breast cancer cells and several drug-resistant breast cancer cell lines, but its role and underlying mechanism for tumor suppression and drug resistance needs further investigation. The current study identifies autophagy as a novel pathway targeted by miR-489 and reports Unc-51 like autophagy activating kinase 1 (ULK1) and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489...
May 21, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29784636/adaptive-nk-cells-resist-regulatory-t-cell-suppression-driven-by-il-37
#19
Dhifaf Sarhan, Keli L Hippen, Amanda Lemire, Skyler Hying, Xianghua Luo, Todd Lenvik, Julie Curtsinger, Zachary Davis, Bin Zhang, Sarah Cooley, Frank Cichocki, Bruce R Blazar, Jeffrey S Miller
Natural Killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Tregs), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FcεRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus (CMV)-exposed individuals...
May 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29784380/fluorescence-activation-imaging-of-localization-distribution-and-level-of-mirna-in-various-organelles-inside-cells
#20
Chuanli Wu, Xiaoyan Liu, Yiyi Zheng, Wenjing He, Guancao Yang, Ping Wu, Chenxin Cai
This work reports an approach for imaging the localization, distribution, and level of miRNA in different organelles based on an activated fluorescence signal triggered by an alteration of the specific binding-induced conformation of the designed activatable probe. We selected miR-150 as an miRNA example to image its localization, distribution, and level in human cervical cancer cells (HeLa cells). The results indicate that miR-150 is localized and distributed in different subcellular organelles (mainly in mitochondria and lysosomes) and that its levels (actually its concentrations) in lysosomes are higher than those in mitochondria in both HeLa and MCF-7 cells...
August 15, 2018: Talanta
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