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gemcitabine resistance

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https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#1
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28917152/pegylated-thermosensitive-lipid-coated-hollow-gold-nanoshells-for-effective-combinational-chemo-photothermal-therapy-of-pancreatic-cancer
#2
Bijay Kumar Poudel, Biki Gupta, Thiruganesh Ramasamy, Raj Kumar Thapa, Shiva Pathak, Kyung Taek Oh, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer...
September 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28912244/potential-role-of-intratumor-bacteria-in-mediating-tumor-resistance-to-the-chemotherapeutic-drug-gemcitabine
#3
Leore T Geller, Michal Barzily-Rokni, Tal Danino, Oliver H Jonas, Noam Shental, Deborah Nejman, Nancy Gavert, Yaara Zwang, Zachary A Cooper, Kevin Shee, Christoph A Thaiss, Alexandre Reuben, Jonathan Livny, Roi Avraham, Dennie T Frederick, Matteo Ligorio, Kelly Chatman, Stephen E Johnston, Carrie M Mosher, Alexander Brandis, Garold Fuks, Candice Gurbatri, Vancheswaran Gopalakrishnan, Michael Kim, Mark W Hurd, Matthew Katz, Jason Fleming, Anirban Maitra, David A Smith, Matt Skalak, Jeffrey Bu, Monia Michaud, Sunia A Trauger, Iris Barshack, Talia Golan, Judith Sandbank, Keith T Flaherty, Anna Mandinova, Wendy S Garrett, Sarah P Thayer, Cristina R Ferrone, Curtis Huttenhower, Sangeeta N Bhatia, Dirk Gevers, Jennifer A Wargo, Todd R Golub, Ravid Straussman
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28898700/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#4
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Serkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
No abstract text is available yet for this article.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28887583/mir-608-regulating-the-expression-of-ribonucleotide-reductase-m1-and-cytidine-deaminase-is-repressed-through-induced-gemcitabine-chemoresistance-in-pancreatic-cancer-cells
#5
Azam Rajabpour, Ali Afgar, Habibollah Mahmoodzadeh, Jalal-E-Din Radfar, Farzad Rajaei, Ladan Teimoori-Toolabi
PURPOSE: Gemcitabine resistance is the main problem in pancreatic adenocarcinoma patients. Hence, we aimed to identify the correlation between expression of RRM1 and CDA as the resistance genes and their predicted targeting miR-608 in the resistant pancreatic cancer cell lines to gemcitabine. METHODS: Dual luciferase assay was performed to determine whether both RRM1 and CDA are targeted by miR-608 in 293T and pancreatic cancer cell lines. AsPC-1 and MIA PaCa-2 cell lines became gradually resistant to gemcitabine by exposing to the increasing doses of gemcitabine...
September 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28885916/calcitriol-reverses-induced-expression-of-efflux-proteins-and-potentiates-cytotoxic-activity-of-gemcitabine-in-capan-2-pancreatic-cancer-cells
#6
Hamed Gilzad-Kohan, Shabnam Sani, Mehdi Boroujerdi
PURPOSE: Efflux and influx proteins play a major role in chemo-resistance by affecting the net cellular uptake of anti-cancer drugs. Hence, alteration of the efflux and influx protein expression may result in variations of chemotherapeutics uptake and consequently cell death rate. The present study investigated the effects of pre-treatment of capan-2 pancreatic cancer cells with calcitriol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) or silibinin on the induction of three major efflux proteins and the main gemcitabine influx protein...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28883618/cg200745-an-hdac-inhibitor-induces-anti-tumour-effects-in-cholangiocarcinoma-cell-lines-via-mirnas-targeting-the-hippo-pathway
#7
Dawoon E Jung, Soo Been Park, Kahee Kim, Chanyang Kim, Si Young Song
Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881737/galeterone-and-its-analogs-inhibit-mnk-eif4e-axis-synergize-with-gemcitabine-impede-pancreatic-cancer-cell-migration-invasion-and-proliferation-and-inhibit-tumor-growth-in-mice
#8
Andrew K Kwegyir-Afful, Francis N Murigi, Puranik Purushottamachar, Vidya P Ramamurthy, Marlena S Martin, Vincent C O Njar
Survival rate for pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is poor, with about 80% of patients presenting with the metastatic disease. Gemcitabine, the standard chemotherapeutic agent for locally advanced and metastatic PDAC has limited efficacy, attributed to innate/acquired resistance and activation of pro-survival pathways. The Mnk1/2-eIF4E and NF-κB signaling pathways are implicated in PDAC disease progression/metastasis and also associated with gemcitabine-induced resistance in PDAC...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28864680/dual-inhibition-of-hedgehog-and-c-met-pathways-for-pancreatic-cancer-treatment
#9
Agnieszka A Rucki, Qian Xiao, Stephen Muth, Jianlin Chen, Xu Che, Jennifer Kleponis, Rajni Sharma, Robert A Anders, Elizabeth M Jaffee, Lei Zheng
Pancreatic adenocarcinoma (PDA) is one of the most chemotherapy and radiotherapy resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has shown promising results in pre-clinical studies; however, the benefits were not readily translated into to clinical trials with PDA patients. In this study, utilizing mouse models of PDA, we showed that inhibition of either HGF/c-Met or Hh pathways sensitize the PDA tumors to gemcitabine resulting in decreased primary tumor volume as well as significant reduction of metastatic tumor burden...
September 1, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28860445/-efficacy-of-gc-therapy-for-the-patient-of-itnbc-with-resistance-to-tac-therapy
#10
Mai Yamada, Makoto Kubo, Masaya Kai, Hidetaka Yamamoto, Masafumi Nakamura
We report a case of TNBC treated effectively with a platinum-based regimen after developing resistance to anthracycline and taxane-based neoadjuvant chemotherapy(NAC). A 59-year-old woman with a right breast mass and high fever visited our clinic and was diagnosed as having inflammatory triple negative breast cancer(iTNBC). She was treated with NAC of docetaxel, doxorubicin, and cyclophosphamide(TAC)using pegfilgrastim. After 5 courses of TAC, the therapy failed and the disease progressed. Thus, a combination regimen of gemcitabine and carboplatin(GC)was administered...
August 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28855593/itga1-is-a-pre-malignant-biomarker-that-promotes-therapy-resistance-and-metastatic-potential-in-pancreatic-cancer
#11
Armen Gharibi, Sa La Kim, Justin Molnar, Daniel Brambilla, Yvess Adamian, Malachia Hoover, Julie Hong, Joy Lin, Laurelin Wolfenden, Jonathan A Kelber
Pancreatic ductal adenocarcinoma (PDAC) has single-digit 5-year survival rates at <7%. There is a dire need to improve pre-malignant detection methods and identify new therapeutic targets for abrogating PDAC progression. To this end, we mined our previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets to identify novel PDAC-specific biomarkers and/or therapeutic targets. We discovered that integrin alpha 1 (ITGA1) is frequently upregulated in pancreatic cancers and associated precursor lesions...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839463/tgf%C3%AE-1-promotes-gemcitabine-resistance-through-regulating-the-lncrna-let-nf90-mir-145-signaling-axis-in-bladder-cancer
#12
Junlong Zhuang, Lan Shen, Lin Yang, Xiaojing Huang, Qun Lu, Yangyan Cui, Xi Zheng, Xiaozhi Zhao, Dianzheng Zhang, Ruimin Huang, Hongqian Guo, Jun Yan
High tumor recurrence is frequently observed in patients with urinary bladder cancers (UBCs), with the need for biomarkers of prognosis and drug response. Chemoresistance and subsequent recurrence of cancers are driven by a subpopulation of tumor initiating cells, namely cancer stem-like cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment remains largely unclear. In this study, we found that during gemcitabine treatment lncRNA-Low Expression in Tumor (lncRNA-LET) was downregulated in chemoresistant UBC, accompanied with the enrichment of CSC population...
2017: Theranostics
https://www.readbyqxmd.com/read/28834399/opioid-tripeptides-hybridized-with-trans-1-cinnamylpiperazine-as-proliferation-inhibitors-of-pancreatic-cancer-cells-in-two-and-three-dimensional-in-vitro-models
#13
Anna K Laskowska, Anna K Puszko, Piotr Sosnowski, Krzysztof Różycki, Piotr Kosson, Joanna Matalińska, Marek Durlik, Aleksandra Misicka
According to the World Health Organization, mortality rate among patients with pancreatic cancer will increase in the upcoming years. Gemcitabine is the first choice for treatment of pancreatic malignancy, but rising resistance to this drug decreases the final outcome. Studies on new therapies targeting metabolic pathways, growth factors inhibitors and tumour stroma or tumour stem cells, are currently underway in many laboratories. Here, we report the bioactive properties (cytotoxicity and haemolytic activity) of synthetic peptidomimetics containing opioid tripeptide fragment (Tyr-X1-X2-; where X1 is D-Ala or D-Thr, and X2 is Phe or Trp) hybridized with trans-1-cinnamylpiperazine...
August 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28814832/combinatorial-and-sequential-delivery-of-gemcitabine-and-oseltamivir-phosphate-from-implantable-poly-d-l-lactic-co-glycolic-acid-cylinders-disables-human-pancreatic-cancer-cell-survival
#14
Stephanie Allison Logan, Amanda J Brissenden, Myron R Szewczuk, Ronald J Neufeld
Combination therapies against multiple targets are currently being developed to prevent resistance to a single chemotherapeutic agent and to extirpate pre-existing resistance in heterogeneous cancer cells in tumors due to selective pressure from the single agent. Gemcitabine (GEM), a chemotherapeutic agent, is the current standard of care for patients with pancreatic cancer. Patients with pancreatic cancer receiving GEM have a low progression-free survival. Given the poor response rate to GEM, cancer cells are known to develop rapid resistance to this drug...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#15
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#16
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28801576/disrupting-glutamine-metabolic-pathways-to-sensitize-gemcitabine-resistant-pancreatic-cancer
#17
Ru Chen, Lisa A Lai, Yumi Sullivan, Melissa Wong, Lei Wang, Jonah Riddell, Linda Jung, Venu G Pillarisetty, Teresa A Brentnall, Sheng Pan
Pancreatic cancer is a lethal disease with poor prognosis. Gemcitabine has been the first line systemic treatment for pancreatic cancer. However, the rapid development of drug resistance has been a major hurdle in gemcitabine therapy leading to unsatisfactory patient outcomes. With the recent renewed understanding of glutamine metabolism involvement in drug resistance and immuno-response, we investigated the anti-tumor effect of a glutamine analog (6-diazo-5-oxo-L-norleucine) as an adjuvant treatment to sensitize chemoresistant pancreatic cancer cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797284/gambogic-acid-sensitizes-gemcitabine-efficacy-in-pancreatic-cancer-by-reducing-the-expression-of-ribonucleotide-reductase-subunit-m2-rrm2
#18
Guanggai Xia, Hongcheng Wang, Ziliang Song, Qingcai Meng, Xiuyan Huang, Xinyu Huang
BACKGROUND: Pancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer...
August 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28796151/potential-development-of-tumor-targeted-oral-anti-cancer-prodrugs-amino-acid-and-dipeptide-monoester-prodrugs-of-gemcitabine
#19
Yasuhiro Tsume, Adam J Drelich, David E Smith, Gordon L Amidon
One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine...
August 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28795274/novel-gemcitabine-conjugated-albumin-nanoparticles-a-potential-strategy-to-enhance-drug-efficacy-in-pancreatic-cancer-treatment
#20
Varun Kushwah, Ashish Kumar Agrawal, Chander Parkash Dora, David Mallinson, Dimitrios A Lamprou, Ramesh C Gupta, Sanyog Jain
PURPOSE: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. METHODS: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis...
August 9, 2017: Pharmaceutical Research
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