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gemcitabine resistance

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https://www.readbyqxmd.com/read/28648516/-mycosis-fungoides-in-a-heart-transplant-recipient
#1
Q Bodard, N Litrowski, D Carre, M Midhat, P Chenal, P Bravard
BACKGROUND: Skin cancer occurs frequently in organ transplant patients as a result of induced immunosuppression. Most cases involve carcinomas or B-cell lymphomas induced by the Epstein Barr virus (EBV). Cutaneous T-cell lymphomas remain rare. We report a case of cutaneous T-cell lymphoma of the mycosis fungoides type in a heart transplant recipient. PATIENTS AND METHODS: A 68-year-old man who had received a heart transplant 21years earlier and was being treated with tacrolimus, mycophenolate mofetil and prednisolone had been presenting a psoriasiform rash on his trunk, limbs and head for 4years...
June 22, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#2
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28638102/mir-509-5p-and-mir-1243-increase-the-sensitivity-to-gemcitabine-by-inhibiting-epithelial-mesenchymal-transition-in-pancreatic-cancer
#3
Hidekazu Hiramoto, Tomoki Muramatsu, Daisuke Ichikawa, Kousuke Tanimoto, Satoru Yasukawa, Eigo Otsuji, Johji Inazawa
The epithelial-mesenchymal transition (EMT) contributes to various processes in cancer progression, such as metastasis and drug resistance. Since we have already established a cell-based reporter system for identifying EMT-suppressive microRNAs (miRNAs) in the pancreatic cancer cell line Panc1, we performed a function-based screening assay by combining this reporter system and a miRNA library composed of 1,090 miRNAs. As a result, we identified miR-509-5p and miR-1243 as EMT-suppressive miRNAs, although the mechanisms for EMT-suppression induced by these miRNAs have yet to be clarified...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607207/lncrna-uca1-in-anti-cancer-drug-resistance
#4
REVIEW
Haohao Wang, Zhonghai Guan, Kuifeng He, Jiong Qian, Jiang Cao, Lisong Teng
The pivotal role of the long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in anti-cancer drug resistance has been confirmed in many cancers. Overexpression of lncRNA UCA1 correlates with resistance to chemotherapeutics such as cisplatin, gemcitabine, 5-FU, tamoxifen, imatinib and EGFR-TKIs, whereas lncRNA UCA1 knockdown restores drug sensitivity. These studies highlight the potential of lncRNA UCA1 as a diagnostic and prognostic biomarker, and a therapeutic target in malignant tumors. In this review, we address the role of lncRNA UCA1 in anti-cancer drug resistance and discuss its potential in future clinical applications...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28599496/use-of-gemcitabine-as-a-second-line-treatment-following-chemotherapy-with-folfirinox-for-metastatic-pancreatic-adenocarcinoma
#5
Matthieu Sarabi, Laetitia Mais, Nadia Oussaid, Françoise Desseigne, Pierre Guibert, Christelle De La Fouchardiere
There is a lack of prospective data about second-line treatments for metastatic pancreatic ductal adenocarcinoma patients. This is partially due to recent changes in first-line chemotherapy treatments. Despite this dearth of information, 50.0% of the patients who experience failure with first-line folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (folfirinox) treatment are eligible for additional chemotherapy. In this setting, gemcitabine is widely used without any standard recommendations available...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599410/resistance-to-nanoparticle-albumin-bound-paclitaxel-is-mediated-by-abcb1-in-urothelial-cancer-cells
#6
Stefan Vallo, Raoul Köpp, Martin Michaelis, Florian Rothweiler, Georg Bartsch, Maximilian P Brandt, Kilian M Gust, Felix Wezel, Roman A Blaheta, Axel Haferkamp, Jindrich Cinatl
Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599178/study-of-small-cell-lung-cancer-cell-based-sensor-and-its-applications-in-chemotherapy-effects-rapid-evaluation-for-anticancer-drugs
#7
Hui Guohua, Lu Hongyang, Jiang Zhiming, Zhu Danhua, Wan Haifang
Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1...
May 31, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28581516/pancreatic-cancer-heterogeneity-and-response-to-mek-inhibition
#8
K Pedersen, F Bilal, C Bernadó Morales, M T Salcedo, T Macarulla, D Massó-Vallés, V Mohan, A Vivancos, M-J Carreras, X Serres, M Abu-Suboh, J Balsells, E Allende, I Sagi, L Soucek, J Tabernero, J Arribas
Our increasing knowledge of the mechanisms behind the progression of pancreatic cancer (PC) has not yet translated into effective treatments. Many promising drugs have failed in the clinic, highlighting the need for better preclinical models to assess drug efficacy and characterize mechanisms of resistance. Using different experimental models, including patient-derived xenografts (PDXs), we gauged the efficacy of therapies aimed at two hallmark lesions of PCs: activation of signaling pathways by oncogenic KRAS and inactivation of tumor-suppressor genes...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28560603/micro-rna-130a-3p-regulates-gemcitabine%C3%A2-resistance-via-pparg-in-cholangiocarcinoma
#9
Kei Asukai, Koichi Kawamoto, Hidetoshi Eguchi, Masamitsu Konno, Ayumu Asai, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Naohiro Nishida, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
BACKGROUND: The prognosis of cholangiocarcinoma (CCA) is so poor that its chemoresistance needs to be reduced. In this study, we focused on the microRNAs (miRNAs) associated with gemcitabine resistance of CCA and assessed the clinical significance of miRNAs and their target genes. METHODS: We performed miRNA microarray analysis for two CCA cell lines (CCLP-1 and MzChA-1) and their gemcitabine-resistant (GR) cells. An miR-130a-3p mimic was induced into CCA cells using lipofection, and we used pioglitazone as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist in vitro...
May 30, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28556483/drug-sensitivity-and-resistance-testing-identifies-plk1-inhibitors-and-gemcitabine-as-potent-drugs-for-malignant-peripheral-nerve-sheath-tumors-mpnst
#10
Matthias Kolberg, Jarle Bruun, Astrid Murumägi, John P Mpindi, Christian H Bergsland, Maren Høland, Ina A Eilertsen, Stine A Danielsen, Olli Kallioniemi, Ragnhild A Lothe
Patients with malignant peripheral nerve sheath tumor (MPNST), a rare soft tissue cancer associated with loss of the tumor suppressor neurofibromin (NF1), have poor prognosis and typically respond poorly to adjuvant therapy. We evaluated the effect of 299 clinical and investigational compounds on seven MPNST cell lines, two primary cultures of human Schwann cells, and five normal bone marrow aspirates, to identify potent drugs for MPNST treatment with few side effects. Top hits included Polo-like kinase 1 (PLK1) inhibitors (volasertib and BI2536) and the fluoronucleoside gemcitabine, which were validated in orthogonal assays measuring viability, cytotoxicity and apoptosis...
May 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28548955/exploring-brusatol-as-a-new-anti-pancreatic-cancer-adjuvant-biological-evaluation-and-mechanistic-studies
#11
Zheng Lu, Zheng-Quan Lai, Albert W N Leung, Po Sing Leung, Zhao-Shen Li, Zhi-Xiu Lin
Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#12
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536008/chemosensitization-and-inhibition-of-pancreatic-cancer-stem-cell%C3%A2-proliferation-by-overexpression-of-microrna-205
#13
Amit Kumar Chaudhary, Goutam Mondal, Virender Kumar, Krishna Kattel, Ram I Mahato
Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R cells. Lentivirus-mediated overexpression of miR-205 inhibits MIA PaCa-2R cell proliferation after GEM-treatment...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28500236/identification-of-the-serine-biosynthesis-pathway-as-a-critical-component-of-braf-inhibitor-resistance-of-melanoma-pancreatic-and-non-small-cell-lung-cancer-cells
#14
Kayleigh C Ross, Andrew J Andrews, Christopher D Marion, Timothy J Yen, Vikram Bhattacharjee
Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFis). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28496342/sialylation-facilitates-self-assembly-of-3d-multicellular-prostaspheres-by-using-cyclo-rgdfk-tpp-peptide
#15
Sabah Haq, Vanessa Samuel, Fiona Haxho, Roman Akasov, Maria Leko, Sergey V Burov, Elena Markvicheva, Myron R Szewczuk
BACKGROUND: Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell-cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking in vivo tumors, the limitations involve no control of assembly and structure with only limited spatial or glandular organization. Here, matrix-free prostaspheres from human metastatic prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP))...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495087/gemcitabine-anti-proliferative-activity-significantly-enhanced-upon-conjugation-with-cell-penetrating-peptides
#16
Nuno Vale, Abigail Ferreira, Iva Fernandes, Cláudia Alves, Maria João Araújo, Nuno Mateus, Paula Gomes
Gemcitabine proven efficiency against a wide range of solid tumors and undergoes deamination to its inactive uridine metabolite, which underlies its low bioavailability, and tumour resistance was also associated with nucleoside transporter alterations. Hence, we have conjugated gemcitabine to cell-penetrating peptides (CPP), in an effort to both mask its aniline moiety and facilitate its delivery into cancer cells. Two CPP-drug conjugates have been synthesized and studied regarding both the time-dependent kinetics of gemcitabine release and their anti-proliferative activity on three different human cancer cell lines...
April 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28492560/mir-218-5p-restores-sensitivity-to-gemcitabine-through-prkce-mdr1-axis-in-gallbladder-cancer
#17
Hui Wang, Ming Zhan, Sun-Wang Xu, Wei Chen, Man-Mei Long, Yong-Heng Shi, Qiang Liu, Man Mohan, Jian Wang
Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28487979/trail-mutant-membrane-penetrating-peptide-alike-mur6-tr-enhances-the-antitumor-effects-of-trail-in-pancreatic-carcinoma-both-in-vitro-and-in-vivo
#18
Lei Sun, Chen Chen, Aijing Zhu, Ying Huang, Hong Zhu, Cheng Yi
To remedy the drug resistance of natural tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and enhance its antitumor effects, we prepared a type of TRAIL mutant membrane penetrating peptide alike (TMPPA)‑TRAIL mutant R6 (MuR6-TR) by mutating the N‑terminal of the soluble TRAIL gene sequence. The expressed MuR6‑TR protein was purified to treat pancreatic carcinoma cell lines BxPC‑3 and PANC‑1. The inhibitory effects on the proliferation of BxPC‑3 and PANC‑1 cells was assessed with CCK‑8 assay and compared with natural TRAIL...
June 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28477403/micro-rna-21-regulates-cancer-associated-fibroblast-mediated-frug-resistance-in-pancreatic-cancer
#19
Lulin Zhang, Jun Yao, Wenyao Li, Ce Zhang
Pancreatic adenocarcinoma (PDAC) is one of the leading cause of cancer death due to its highly aggressive biological nature and resistance to chemotherapies. Former study also indicated that miR-21 in cancer-associated fibroblasts (CAFs) is an important regulator of their activation. However, whether miR-21 in CAFs would regulate PDAC's tumor microenvironment and leading to drug resistance remain unknown. In this study, we evaluated the relationship among CAFs activation, miR-21 expression level and drug resistance using PDAC patient tumor samples...
May 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28469793/downregulation-of-mir-301a-3p-sensitizes-pancreatic-cancer-cells-to-gemcitabine-treatment-via-pten
#20
Xiang Xia, Kundong Zhang, Guangtao Luo, Gang Cen, Jun Cao, Kejian Huang, Zhengjun Qiu
BACKGROUND: We previously showed that miR-301a-3p affects the invasion and migration abilities of pancreatic cancer cells. Here, we explore the role of miR-301a-3p in chemoresistance, which represents a major obstacle in cancer treatment. METHODS: We tested the effects of miR-301a-3p ongemcitabine resistance in cytotoxicity assays in vitro and in vivo. We used quantitative real-time PCR (qRT-PCR) to measure miR-301a-3p expression in wild-type and gemcitabine-resistant pancreatic cancer cells...
2017: American Journal of Translational Research
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