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https://www.readbyqxmd.com/read/29161243/the-combined-activation-of-kca3-1-and-inhibition-of-kv11-1-herg1-currents-contribute-to-overcome-cisplatin-resistance-in-colorectal-cancer-cells
#1
Serena Pillozzi, Massimo D'Amico, Gianluca Bartoli, Luca Gasparoli, Giulia Petroni, Olivia Crociani, Tiziano Marzo, Angela Guerriero, Luigi Messori, Mirko Severi, Roberto Udisti, Heike Wulff, K George Chandy, Andrea Becchetti, Annarosa Arcangeli
BACKGROUND: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K(+) channel modulators on colorectal cancer (CRC) cells. METHODS: The functional expression of Ca(2+)-activated (KCa3.1, also known as KCNN4) and voltage-dependent (Kv11...
November 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29161238/downregulation-of-inhibition-of-apoptosis-stimulating-protein-of-p53-iaspp-suppresses-cisplatin-resistant-gastric-carcinoma-in-vitro
#2
Jianyong Yu, Li Li, Chengsuo Huang
BACKGROUND Gastric cancer (GC) with cisplatin resistance is one of the leading causes of limitations to therapy. Inhibition of apoptosis-stimulating protein of p53 (iASPP) plays a key role in GC. However, the role of iASPP in GC with cisplatin resistance remains unclear. The aim of this study was to investigate iASPP expression in GC, and the functions of iASPP in cisplatin-resistant cell lines. MATERIAL AND METHODS In this study, the expression of iASPP was investigated in normal GC patients and patients with cisplatin resistance, along with GC cell lines and cell lines with cisplatin resistance...
November 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29160846/a-triphenylphosphonium-functionalized-mitochondriotropic-nanocarrier-for-efficient-co-delivery-of-doxorubicin-and-chloroquine-and-enhanced-antineoplastic-activity
#3
Katerina N Panagiotaki, Zili Sideratou, Spiros A Vlahopoulos, Maria Paravatou-Petsotas, Michael Zachariadis, Nikolas Khoury, Vassilis Zoumpourlis, Dimitris Tsiourvas
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication...
November 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29160717/reprogramming-tumor-associated-macrophages-to-reverse-egfr-t790m-resistance-by-dual-targeting-codelivery-of-gefitinib-vorinostat
#4
Huige Peng, Binfan Chen, Wei Huang, Yubo Tang, Yifan Jiang, Wenyuan Zhang, Yongzhuo Huang
Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR(T790M) mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR(T790M)-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR(T790M)-associated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells...
November 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/29160412/exosomes-promote-cetuximab-resistance-via-the-pten-akt-pathway-in-colon-cancer-cells
#5
S Zhang, Y Zhang, J Qu, X Che, Y Fan, K Hou, T Guo, G Deng, N Song, C Li, X Wan, X Qu, Y Liu
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29159872/the-dark-side-of-glucose-transporters-in-prostate-cancer-are-they-a-new-feature-to-characterize-carcinomas
#6
REVIEW
Pedro Gonzalez-Menendez, David Hevia, Juan C Mayo, Rosa M Sainz
One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29159771/cldn6-enhances-chemoresistance-to-adm-via-af-6-erks-pathway-in-tnbc-cell-line-mdamb231
#7
Minlan Yang, Yanru Li, Yang Ruan, Yan Lu, Dongjing Lin, Yinping Xie, Bing Dong, Qihua Dang, Chengshi Quan
Claudin-6 (CLDN6), a critical tight junction protein acting as a tumor suppressor in breast cancer, is also considered to be a stem cell marker. Triple-negative breast cancer (TNBC) is a subtype of claudin-low and stem cell-like breast cancer which is chemoresistant to multiple anti-cancer drugs. The aim of our study was to determine whether CLDN6 plays a role in chemoresistance of TNBC. We found that overexpression of CLDN6 in TNBC cell line MDAMB231 significantly inhibited cell growth, migration, and invasion...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29159512/cell-sheet-based-multilayered-liver-tumor-models-for-anti-cancer-drug-screening
#8
Jianing Yang, Shengjun Zhao, Yunfei Ji, Lili Zhao, Qingzhu Kong, Qing Zhang
OBJECTIVE: To fabricate in vitro cell-dense, three-dimensional (3D) tumor models by employing a cell sheet technology for testing anti-cancer drug efficacy. RESULTS: The stratified liver tumor models were fabricated by stacking contiguous HepG2 cell sheets. Triple-layer (3L), double-layer (2L), single-layer (1L) cell sheet-based liver tumor models (CSLTMs) demonstrated 106, 96, 85% cell viability, respectively, after 3 days treatment of 10 µM doxorubicin hydrochloride (DOX), while cell viability in two-dimensional (2D) conventional culture (control) was 27%...
November 20, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/29159318/young-donor-white-blood-cell-immunotherapy-induces-extensive-tumor-necrosis-in-advanced-stage-solid-tumors
#9
Dipnarine Maharaj, Pedro G Vianna, Wendy Ward, Anthony J Messina, Trevor Rayborn, Jacqueline V Gouvea, Richard D Hammer, Zheng Cui
Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68-91% granulocytes) collected by leukapheresis from young, healthy donors (age 18-35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone...
October 2017: Heliyon
https://www.readbyqxmd.com/read/29159146/lactobacillus-plantarum-induces-apoptosis-in-oral-cancer-kb-cells-through-upregulation-of-pten-and-downregulation-of-mapk-signalling-pathways
#10
Abbas Asoudeh-Fard, Abolfazl Barzegari, Alireza Dehnad, Sepideh Bastani, Asal Golchin, Yadollah Omidi
Introduction: The oral tumor is the sixth most prevalent type of cancer worldwide and the second leading cause of cancer-related mortality. Although chemotherapy and immunotherapy are the main strategies for the treatment of oral cancer, an emergence of inevitable resistance to these treatment modalities is the major drawback that causes recurrence of the disease. Nowadays, probiotics have been suggested as adjunctive and complementary treatment modalities for improving the impacts of chemotherapy and immunotherapy agents...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/29158964/ginsenoside-rk1-bioactivity-a-systematic-review
#11
Abdelrahman Elshafay, Ngo Xuan Tinh, Samar Salman, Yara Saber Shaheen, Eman Bashir Othman, Mohamed Tamer Elhady, Aswin Ratna Kansakar, Linh Tran, Le Van, Kenji Hirayama, Nguyen Tien Huy
Ginsenoside Rk1 (G-Rk1) is a unique component created by processing the ginseng plant (mainly Sung Ginseng (SG)) at high temperatures. The aim of our study was to systematically review the pharmacological effects of G-Rk1. We utilized and manually searched eight databases to select in vivo and in vitro original studies that provided information about biological, pharmaceutical effects of G-Rk1 and were published up to July 2017 with no restriction on language or study design. Out of the 156 papers identified, we retrieved 28 eligible papers in the first skimming phase of research...
2017: PeerJ
https://www.readbyqxmd.com/read/29158842/locoregional-confinement-and-major-clinical-benefit-of-188-re-loaded-cxcr4-targeted-nanocarriers-in-an-orthotopic-human-to-mouse-model-of-glioblastoma
#12
Delphine Séhédic, Igor Chourpa, Clément Tétaud, Audrey Griveau, Claire Loussouarn, Sylvie Avril, Claire Legendre, Nicolas Lepareur, Didier Wion, François Hindré, François Davodeau, Emmanuel Garcion
PURPOSE: Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated...
2017: Theranostics
https://www.readbyqxmd.com/read/29158832/clinical-translation-and-first-in-human-use-of-44-sc-sc-psma-617-for-pet-imaging-of-metastasized-castrate-resistant-prostate-cancer
#13
Elisabeth Eppard, Ana de la Fuente, Martina Benešová, Ambreen Khawar, Ralph A Bundschuh, Florian C Gärtner, Barbara Kreppel, Klaus Kopka, Markus Essler, Frank Rösch
BACKGROUND: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications...
2017: Theranostics
https://www.readbyqxmd.com/read/29158829/past-present-and-future-development-of-theranostic-agents-targeting-carbonic-anhydrase-ix
#14
REVIEW
Joseph Lau, Kuo-Shyan Lin, François Bénard
Theranostics is the integration of diagnostic information with pharmaceuticals to increase effectiveness and safety of cancer treatments. Nuclear medicine provides a non-invasive means to visualize drug target expression across primary and metastatic sites, and assess pharmacokinetics and efficacy of companion therapeutic agents. This is significant given the increasing recognition of the importance of clonal heterogeneity in treatment response and resistance. Carbonic anhydrase IX (CA-IX) has been advocated as an attractive diagnostic and therapeutic biomarker for targeting hypoxia in solid malignancies...
2017: Theranostics
https://www.readbyqxmd.com/read/29158820/ph-sensitive-nano-complexes-overcome-drug-resistance-and-inhibit-metastasis-of-breast-cancer-by-silencing-akt-expression
#15
Jieying Yin, Tianqun Lang, Dongmei Cun, Zhong Zheng, Yan Huang, Qi Yin, Haijun Yu, Yaping Li
The therapy of breast cancer is encumbered by drug resistance and metastasis, which can be due to a defective PI3K/AKT/mTOR signaling pathway. This study was aimed at improving the anti-cancer effect of the chemotherapeutic agent paclitaxel (PTX) on the drug resistant and metastatic breast cancer by co-delivering PTX and a siRNA, siAkt, directed at silencing the Akt expression. Methods: The pH-sensitive amphiphilic polymer, poly [(1,4-butanediol)-diacrylate-β-N, N-diisopropylethylenediamine]-polyethyleneimine (BDP) was synthesized...
2017: Theranostics
https://www.readbyqxmd.com/read/29158814/dna-methylation-of-mir-7-is-a-mechanism-involved-in-platinum-response-through-mafg-overexpression-in-cancer-cells
#16
Olga Vera, Julia Jimenez, Olga Pernia, Carlos Rodriguez-Antolin, Carmen Rodriguez, Fatima Sanchez Cabo, Javier Soto, Rocio Rosas, Sara Lopez-Magallon, Isabel Esteban Rodriguez, Ana Dopazo, Federico Rojo, Cristobal Belda, Rafael Alvarez, Jaime Valentin, Javier Benitez, Rosario Perona, Javier De Castro, Inmaculada Ibanez de Caceres
One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines...
2017: Theranostics
https://www.readbyqxmd.com/read/29158813/vascularized-tissue-engineered-model-for-studying-drug-resistance-in-neuroblastoma
#17
A Villasante, K Sakaguchi, J Kim, N K Cheung, M Nakayama, H Parsa, T Okano, T Shimizu, G Vunjak-Novakovic
Neuroblastoma is a vascularized pediatric tumor derived from neural crest stem cells that displays vasculogenic mimicry and can express a number of stemness markers, such as SOX2 and NANOG. Tumor relapse is the major cause of succumbing to this disease, and properties attributed to cancer stem-like cells (CSLC), such as drug-resistance and cell plasticity, seem to be the key mechanisms. However, the lack of controllable models that recapitulate the features of human neuroblastoma limits our understanding of the process and impedes the development of new therapies...
2017: Theranostics
https://www.readbyqxmd.com/read/29158811/transforming-doxorubicin-into-a-cancer-stem-cell-killer-via-epcam-aptamer-mediated-delivery
#18
Dongxi Xiang, Sarah Shigdar, Andrew G Bean, Matthew Bruce, Wenrong Yang, Motilal Mathesh, Tao Wang, Wang Yin, Phuong Ha-Lien Tran, Hadi Al Shamaileh, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Aina He, Wei Duan
Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX...
2017: Theranostics
https://www.readbyqxmd.com/read/29158806/correlation-of-aldh1-and-notch3-expression-clinical-implication-in-ovarian-carcinomas
#19
Mi Joung Kim, A-Ram Kim, Ju-Yeon Jeong, Kwang-Il Kim, Tae-Heon Kim, Chan Lee, Kwanghoe Chung, Young-Hyeh Ko, Hee-Jung An
Purpose : ALDH1 is a putative cancer stem cell marker, while the Notch signaling pathway is involved in regulation of cancer stem cell (CSC)s. This study aims to determine the expression of Notch signaling genes in ovarian CSCs, and to assess the clinical impact of expression of ALDH1 and Notch signaling genes in ovarian cancers. Methods : We examined expression of Notch signaling genes in FACS-sorted ALDH1(+) putative ovarian CSCs and expression of ALDH1 and Notch signaling genes in 86 ovarian epithelial tumors and various ovarian cancer cell lines by real-time RT-PCR, including Notch receptors (Notch1-4), Notch ligands (Jagged1 and Jagged2), and the downstream molecule, Hes1...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158802/cytokine-induced-killer-cells-modulates-resistance-to-cisplatin-in-the-a549-ddp-cell-line
#20
Lili Yang, Chunjuan Du, Lei Wu, Jinpu Yu, Xiumei An, Wenwen Yu, Shui Cao, Hui Li, Xiubao Ren
Background Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. Objective This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. Methods The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed in vitro. Results After A549/DDP co-culture with CIK cells, the DDP resistance of A549/DDP significantly decreased in a time-dependent manner...
2017: Journal of Cancer
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