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https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#1
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28101932/amino-acid-profiling-of-zinc-resistant-prostate-cancer-cell-lines-associations-with-cancer-progression
#2
Monika Kratochvilova, Martina Raudenska, Zbynek Heger, Lukas Richtera, Natalia Cernei, Vojtech Adam, Petr Babula, Marie Novakova, Michal Masarik, Jaromir Gumulec
BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28101802/cold-pcr-technologies-in-the-area-of-personalized-medicine-methodology-and-applications
#3
REVIEW
Florence Mauger, Alexandre How-Kit, Jörg Tost
Somatic mutations bear great promise for use as biomarkers for personalized medicine, but are often present only in low abundance in biological material and are therefore difficult to detect. Many assays for mutation analysis in cancer-related genes (hotspots) have been developed to improve diagnosis, prognosis, prediction of drug resistance, and monitoring of the response to treatment. Two major approaches have been developed: mutation-specific amplification methods and methods that enrich and detect mutations without prior knowledge on the exact location and identity of the mutation...
January 18, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28101198/elevated-expression-of-nrf2-mediates-multidrug-resistance-in-cd133-head-and-neck-squamous-cell-carcinoma-stem-cells
#4
Bao-Cai Lu, Jing Li, Wen-Fa Yu, Guo-Zheng Zhang, Hui-Min Wang, Hui-Min Ma
Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101173/particularly-interesting-cys-his-rich-protein-is-highly-expressed-in-human-intracranial-aneurysms-and-resists-aneurysmal-rupture
#5
Yu-Tao Peng, Xiang-En Shi, Zhi-Qiang Li, Xin He, Yu-Ming Sun
Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101169/role-of-wnt-%C3%AE-catenin-wnt-c-jun-n-terminal-kinase-and-wnt-ca-2-pathways-in-cisplatin-induced-chemoresistance-in-ovarian-cancer
#6
Lu Huang, Ye Jin, Shujun Feng, Yuqing Zou, Sainan Xu, Shuang Qiu, Ling Li, Jianhua Zheng
The aim of the present study was to explore the expression of Wnt signaling proteins β-catenin, c-Jun N-terminal kinase (JNK) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin-induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR-99021, glycogen synthase kinase 3β inhibitor) or inhibitor (XAV-939, tankyrase inhibitor)...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100854/the-role-of-cancer-stem-cells-in-pathogenesis-of-colorectal-cancer
#7
Magdalena Szaryńska, Agata Olejniczak, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most commonly diagnosed cancer, accounting for about 10% of total adult malignancies worldwide. The majority of CRC cases are diagnosed at the late stage; thus the investigation of the pathogenesis of early-stage disease and its detection could prevent formation of metastasis, a leading cause of death. This review highlights the recent progress in the understanding of the development of cancer stem cells (CSCs) in the colon epithelium and mechanisms of their proliferation...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100566/loss-of-axin1-drives-acquired-resistance-to-wnt-pathway-blockade-in-colorectal-cancer-cells-carrying-rspo3-fusions
#8
Gabriele Picco, Consalvo Petti, Alessia Centonze, Erica Torchiaro, Giovanni Crisafulli, Luca Novara, Andrea Acquaviva, Alberto Bardelli, Enzo Medico
In colorectal cancer (CRC), WNT pathway activation by genetic rearrangements of RSPO3 is emerging as a promising target. However, its low prevalence severely limits availability of preclinical models for in-depth characterization. Using a pipeline designed to suppress stroma-derived signal, we find that RSPO3 "outlier" expression in CRC samples highlights translocation and fusion transcript expression. Outlier search in 151 CRC cell lines identified VACO6 and SNU1411 cells as carriers of, respectively, a canonical PTPRK(e1)-RSPO3(e2) fusion and a novel PTPRK(e13)-RSPO3(e2) fusion...
January 18, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28100259/antitumor-activity-of-mir-34a-in-peritoneal-mesothelioma-relies-on-c-met-and-axl-inhibition-persistent-activation-of-erk-and-akt-signaling-as-a-possible-cytoprotective-mechanism
#9
Rihan El Bezawy, Michelandrea De Cesare, Marzia Pennati, Marcello Deraco, Paolo Gandellini, Valentina Zuco, Nadia Zaffaroni
BACKGROUND: The value of microRNAs (miRNAs) as novel targets for cancer therapy is now widely recognized. However, no information is currently available on the expression/functional role of miRNAs in diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional treatments, for which the development of new therapeutic strategies is urgently needed. Here, we evaluated the expression and biological effects of miR-34a-one of the most widely deregulated miRNAs in cancer and for which a lipid-formulated mimic is already clinically available-in a large cohort of DMPM clinical samples and a unique collection of in house-developed preclinical models, with the aim to assess the potential of a miR-34a-based approach for disease treatment...
January 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#10
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28100096/targeting-therapy-resistant-cancer-stem-cells-by-hyperthermia
#11
A L Oei, L E M Vriend, P M Krawczyk, M R Horsman, N A P Franken, J Crezee
Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumor that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumor initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited...
January 19, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#12
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099902/anthelmintic-mebendazole-enhances-cisplatin-s-effect-on-suppressing-cell-proliferation-and-promotes-differentiation-of-head-and-neck-squamous-cell-carcinoma-hnscc
#13
Fugui Zhang, Yong Li, Hongmei Zhang, Enyi Huang, Lina Gao, Wenping Luo, Qiang Wei, Jiaming Fan, Dongzhe Song, Junyi Liao, Yulong Zou, Feng Liu, Jianxiang Liu, Jiayi Huang, Dan Guo, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Tingting Wu, Hue H Luu, Rex C Haydon, Jinlin Song, Tong-Chuan He, Ping Ji
Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#14
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28099785/a-dual-topoisomerase-inhibitor-of-intense-pro-apoptotic-and-antileukemic-nature-for-cancer-treatment
#15
Christopher Meier, Tamara N Steinhauer, Fabian Koczian, Birte Plitzko, Katharina Jarolim, Ulrich Girreser, Simone Braig, Doris Marko, Angelika M Vollmar, Bernd Clement
Classic cytotoxic drugs constantly remain an indispensable instrument in antitumor therapy due to their effectiveness and a more prevalent insensibility against tumor resistance mechanisms. We describe the favorable properties of P8-D6, a powerful inductor of apoptosis caused by an equipotent inhibition of human topoisomerase I and II activities. A broad spectrum effect against human tumor cell lines in nanomolar concentrations as well as strong anti-leukemic effects were shown and proven to be superior to marketed topo-targeting drugs and dual topoisomerase inhibitors in clinical trials...
January 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28099443/inhibition-of-human-drug-transporter-activities-by-the-pyrethroid-pesticides-allethrin-and-tetramethrin
#16
Lisa Chedik, Arnaud Bruyere, Marc Le Vee, Bruno Stieger, Claire Denizot, Yannick Parmentier, Sophie Potin, Olivier Fardel
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells...
2017: PloS One
https://www.readbyqxmd.com/read/28099441/puma-and-nf-kb-are-cell-signaling-predictors-of-reovirus-oncolysis-of-breast-cancer
#17
Chandini Thirukkumaran, Zhong-Qiao Shi, Ponnampalam Thirukkumaran, Joanne Luider, Karen Kopciuk, Jason Spurrell, Kate Elzinga, Don Morris
BACKGROUND AND PURPOSE: Reovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour...
2017: PloS One
https://www.readbyqxmd.com/read/28099142/the-pentapeptide-gly-thr-gly-lys-thr-confers-sensitivity-to-anti-cancer-drugs-by-inhibition-of-cage-binding-to-gsk3%C3%AE-and-decreasing-the-expression-of-cyclind1
#18
Youngmi Kim, Hyuna Kim, Deokbum Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Doyong Jeon, Dooil Jeoung
We previously reported the role of cancer/testis antigen CAGE in the response to anti-cancer drugs. CAGE increased the expression of cyclinD1, and pGSK3βSer9, an inactive GSK3β, while decreasing the expression of phospho-cyclinD1Thr286. CAGE showed binding to GSK3β and the domain of CAGE (amino acids 231-300) necessary for binding to GSK3β and for the expression regulation of cyclinD1 was determined. 269GTGKT273 peptide, corresponding to the DEAD box helicase domain of CAGE, decreased the expression of cyclinD1 and pGSK3βSer9 while increasing the expression of phospho-cyclinD1Thr286...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098863/effect-and-mechanism-of-resveratrol-on-drug-resistance-in-human-bladder-cancer-cells
#19
Shanshan Wang, Qian Meng, Qing Xie, Man Zhang
Multidrug resistance (MDR) is a significant barrier to the effective treatment of bladder cancer. In order to improve the management of bladder cancer, it is crucial to identify strategies that may reverse MDR. The effects of three herbal medicines, ginsenoside Rh2, (‑)‑epigallocatechin gallate (EGCG) and resveratrol (RES) on bladder cancer were determined. The effect of these three herbal medicines against the drug resistance in adriamycin (ADM)‑resistant pumc‑91 cells (pumc‑91/ADM) was assessed using the Cell Counting Kit‑8 cell proliferation assay system...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098816/estrogen-enhances-the-expression-of-the-multidrug-transporter-gene-abcg2-increasing-drug-resistance-of-breast-cancer-cells-through-estrogen-receptors
#20
Fung-Wei Chang, Hueng-Chuen Fan, Jui-Ming Liu, Tai-Ping Fan, Jin Jing, Chia-Ling Yang, Ren-Jun Hsu
BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line...
January 14, 2017: International Journal of Molecular Sciences
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