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https://www.readbyqxmd.com/read/28476028/hif-2%C3%AE-dictates-the-susceptibility-of-pancreatic-cancer-cells-to-trail-by-regulating-survivin-expression
#1
Nanae Harashima, Keizo Takenaga, Miho Akimoto, Mamoru Harada
Cancer cells develop resistance to therapy by adapting to hypoxic microenvironments, and hypoxia-inducible factors (HIFs) play crucial roles in this process. We investigated the roles of HIF-1α and HIF-2α in cancer cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) using human pancreatic cancer cell lines. siRNA-mediated knockdown of HIF-2α, but not HIF-1α, increased susceptibility of two pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL in vitro under normoxic and hypoxic conditions...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430580/expression-status-of-folate-receptor-alpha-is-a-predictor-of-survival-in-pancreatic-ductal-adenocarcinoma
#2
Lei Cai, Theodoros Michelakos, Cristina R Ferrone, Liyuan Zhang, Vikram Deshpande, Qi Shen, Albert De Leo, Teppei Yamada, Gong Zhang, Soldano Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognosis among malignancies. Thus, the identification of markers useful in developing innovative diagnostic and therapeutic methods is an imperative need. Folate receptor alpha (FRα) has been associated with prognosis in several cancers and has served as a target of novel anti-tumor therapies. However, FRα expression in PDAC and its correlation with the clinical course of the disease has not been thoroughly investigated. In this study, we analyzed FRα expression in 140 PDAC specimens and 7 PDAC cell lines in order to define the significance of FRα expression in PDAC and its potential role as a target for immunotherapy...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416605/photodynamic-therapy-using-photosensitizer-encapsulated-polymeric-nanoparticle-to-overcome-atp-binding-cassette-transporter-subfamily-g2-function-in-pancreatic-cancer
#3
Yoon Jin Roh, Ju Hee Kim, In-Wook Kim, Kun Na, Jae Myung Park, Myung-Gyu Choi
Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT).  These drugs are effluxed by cell-membrane transporters, such as the ATP-binding cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT efficacy between Chlorin e6 (Ce6) and cationic photosensitizer-encapsulated polymeric nanoparticle (PS-pNP) which is comprised with Ce6, polyethylene glycol and polyethylenimine...
April 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28395150/4-indolyl-n-hydroxyphenylacrylamides-as-potent-hdac-class-i-and-iib-inhibitors-in%C3%A2-vitro-and-in%C3%A2-vivo
#4
Samir Mehndiratta, Ruei-Shian Wang, Han-Li Huang, Chih-Jou Su, Chia-Ming Hsu, Yi-Wen Wu, Shiow-Lin Pan, Jing-Ping Liou
A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28 nM and 1.34 nM) and HDAC 2 (IC50 0.90 and 0.53 nM). N-Hydroxy-3-{4-[2-(1H-indol-4-yl)-ethylsulfamoyl]-phenyl}-acrylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI50 of 0.14, 0.25, 0.32, and 0.24 μM, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62...
March 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28381166/downregulation-of-microrna-181d-had-suppressive-effect-on-pancreatic-cancer-development-through-inverse-regulation-of-knain2
#5
Guopeng Zhang, Dongbo Liu, Guoxian Long, Lei Shi, Hong Qiu, Guangyuan Hu, Guoqing Hu, Shunfang Liu
We explored the expression and function of miR-181d (microRNA-181d) in human pancreatic cancer. Quantitative real-time polymerase chain reaction was used to probe miR-181d expression in both pancreatic cancer cell lines and human pancreatic carcinoma. Pancreatic cancer cell lines, PANC-1 and AsPC-1 cells, were engineered to stably downregulate endogenous miR-181d through lentiviral transduction. The mechanistic effects of miR-181d downregulation on pancreatic cancer development were tested by proliferation, migration, fluorouracil chemosensitivity assays in vitro, and explant assay in vivo...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28374987/swollen-micelles-for-the-preparation-of-gated-squeezable-ph-responsive-drug-carriers
#6
Jian-Bo Qu, Robert Chapman, Fan Chen, Hongxu Lu, Martina H Stenzel
Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nanocarriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH...
April 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28368050/tm4sf1-promotes-metastasis-of-pancreatic-cancer-via-regulating-the-expression-of-ddr1
#7
Jia-Chun Yang, Yi Zhang, Si-Jia He, Ming-Ming Li, Xiao-Lei Cai, Hui Wang, Lei-Ming Xu, Jia Cao
Transmembrane-4-L-six-family-1(TM4SF1), a four-transmembrane L6 family member, is highly expressed in various pancreatic cancer cell lines and promotes cancer cells metastasis. However, the TM4SF1-associated signaling network in metastasis remains unknown. In the present study, we found that TM4SF1 affected the formation and function of invadopodia. Silencing of TM4SF1 reduced the expression of DDR1 significantly in PANC-1 and AsPC-1 cells. Through double fluorescence immuno-staining and Co-immunoprecipitation, we also found that TM4SF1 colocalized with DDR1 and had an interaction with DDR1...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28349057/interleukin-9-promotes-pancreatic-cancer-cells-proliferation-and-migration-via-the-mir-200a-beta-catenin-axis
#8
Bangli Hu, Huang Qiu-Lan, Rong-E Lei, Cheng Shi, Hai-Xing Jiang, Shan-Yu Qin
Background. Both IL-9 and miR-200a are involved in the pathogenesis of cancers; however, the role of IL-9 in pancreatic cancer and the possible underlying mechanisms remain unknown. The aim of this study was to investigate the effect of IL-9 on pancreatic cancer cells and its interaction with miR-200a. Methods. Pancreatic cancer cells (PANC-1 and AsPC-1) were treated with IL-9 and the expression of miR-200a and β-catenin in pancreatic cancer cells was measured. β-Catenin was examined as a target gene of miR-200a in pancreatic cancer cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28328015/pcsk9-inhibitor-access-barriers-issues-and-recommendations-improving-the-access-process-for-patients-clinicians-and-payers
#9
REVIEW
Seth J Baum, Peter P Toth, James A Underberg, Paul Jellinger, Joyce Ross, Katherine Wilemon
The proprotein convertase subtilisin/kexin type 9 inhibitors or monoclonal antibodies likely represent the greatest advance in lipid management in 30 years. In 2015 the US Food and Drug Administration approved both alirocumab and evolocumab for high-risk patients with familial hypercholesterolemia (FH) and clinical atherosclerotic cardiovascular disease requiring additional lowering of low-density lipoprotein cholesterol. Though many lipid specialists, cardiovascular disease prevention experts, endocrinologists, and others prescribed the drugs on label, they found their directives denied 80% to 90% of the time...
April 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28325302/aptamer-drug-conjugates-of-active-metabolites-of-nucleoside-analogs-and-cytotoxic-agents-inhibit-pancreatic-tumor-cell-growth
#10
Sorah Yoon, Kai-Wen Huang, Vikash Reebye, Duncan Spalding, Teresa M Przytycka, Yijie Wang, Piotr Swiderski, Lin Li, Brian Armstrong, Isabella Reccia, Dimitris Zacharoulis, Konstantinos Dimas, Tomokazu Kusano, John Shively, Nagy Habib, John J Rossi
Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic cancer RNA aptamer P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated to monomethyl auristatin E (MMAE) and derivative of maytansine 1 (DM1)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#11
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28135095/analogues-of-the-potent-antitumor-compound-leiodermatolide-from-a-deep-water-sponge-of-the-genus-leiodermatium
#12
Amy E Wright, Jill C Roberts, Esther A Guzmán, Tara P Pitts, Shirley A Pomponi, John K Reed
Two new analogues of the potent antitumor compound leiodermatolide, which we call leiodermatolides B and C, have been isolated from specimens of a deep-water sponge of the genus Leiodermatium collected off Florida. The compounds were purified using standard chromatographic methods, and the structures defined through interpretation of the HRMS and 1D and 2D NMR data. Leiodermatolide B (2) lacks the C-21 hydroxy group found in leiodermatolide and has equal potency as the parent compound, providing a simpler analogue for possible clinical development...
January 30, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28112370/the-jak-stat-pathway-is-involved-in-the-upregulation-of-pd-l1-expression-in-pancreatic-cancer-cell-lines
#13
Toshifumi Doi, Takeshi Ishikawa, Tetsuya Okayama, Kaname Oka, Katsura Mizushima, Tomoyo Yasuda, Naoyuki Sakamoto, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Yuji Naito, Yoshito Itoh
Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28095588/potent-effects-of-dioscin-against-pancreatic-cancer-via-mir-149-3p-mediated-inhibition-of-the-akt1-signalling-pathway
#14
Lingling Si, Lina Xu, Lianhong Yin, Yan Qi, Xu Han, Youwei Xu, Yanyan Zhao, Kexin Liu, Jinyong Peng
BACKGROUND AND PURPOSE: The aim of the present study was to investigate the effects and possible underlying mechanisms of dioscin against pancreatic cancer in vitro and in vivo. EXPERIMENTAL APPROACH: In vitro actions of dioscin on viability of ASPC-1 and PANC-1 cells, and in vivo effects to suppress the tumour growth of cell xenografts in nude mice were assessed. In addition, microRNA microarray analysis determined which microRNAs were affected by dioscin. The mechanisms underlying the actions of dioscin against pancreatic cancer were elucidated in terms of Akt1 and other proteins related to aopoptosis...
April 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#15
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28060183/gemcitabine-enhances-kras-mek-induced-matrix-metalloproteinase-10-expression-via-histone-acetylation-in-gemcitabine-resistant-pancreatic-tumor-initiating-cells
#16
Kazuya Shimizu, Takaaki Nishiyama, Yuichi Hori
OBJECTIVES: Advanced pancreatic ductal adenocarcinoma is resistant to systemic chemotherapy, resulting in a poor prognosis. We previously isolated a human pancreatic tumor-initiating cell line, KMC07, from a patient with acquired resistance to gemcitabine chemotherapy. To improve the anticancer effects of gemcitabine, we investigated the molecular mechanism of KMC07 cells' resistance to gemcitabine. METHODS: KMC07 cells were treated with gemcitabine, then gene expression and functional analyses performed using microarray, the quantitative polymerase chain reaction, immunoblotting, immunohistochemistry, chromatin immunoprecipitation, and cell transplantation into nude mice...
February 2017: Pancreas
https://www.readbyqxmd.com/read/27999190/leptin-notch-signaling-axis-is-involved-in-pancreatic-cancer-progression
#17
Adriana Harbuzariu, Antonio Rampoldi, Danielle S Daley-Brown, Pierre Candelaria, Tia L Harmon, Crystal C Lipsey, Derrick J Beech, Alexander Quarshie, Gabriela Oprea Ilies, Ruben R Gonzalez-Perez
Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2)...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27977086/report-summary-mood-and-anxiety-disorders-in-canada-2016
#18
L McRae, S O'Donnell, L Loukine, N Rancourt, C Pelletier
Mood and Anxiety Disorders in Canada, 2016 is the first publication to include administrative health data from the Canadian Chronic Disease Surveillance System (CCDSS) for the national surveillance of mood and anxiety disorders among Canadians aged one year and older. It features nationally complete CCDSS data up to fiscal year 2009/10, as well as trend data spanning over a decade (1996/97 to 2009/10). The data presented in this report, and subsequent updates, can be accessed via the Public Health Agency of Canada's Chronic Disease Infobase Data Cubes at www...
December 2016: Health Promotion and Chronic Disease Prevention in Canada
https://www.readbyqxmd.com/read/27936486/microrna-4656-is-a-prognostic-factor-and-tumor-suppressor-in-human-pancreatic-cancer-through-a-downstream-target-of-trka
#19
Xianglong Tan, Jinyong Lv, Guodong Zhao, Zhiming Zhao, Chenggang Li, Yong Xu, Minggen Hu
BACKGROUND: In the present study, we investigated the expression profile and functional mechanism of microRNA-4656 in human pancreatic cancer (PC). METHODS: MiR-4656 expression in PC tumors was examined using a quantitative reverse transcriptase-polymerase chain reaction in 134 patients. Associations between tumorous miR-4656 expression and clinicopathological parameters of patients, as well as overall survival, were analyzed. MiR-4656 expression was also examined in PC in vitro cell lines...
January 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/27936114/long-circulating-curcumin-loaded-liposome-formulations-with-high-incorporation-efficiency-stability-and-anticancer-activity-towards-pancreatic-adenocarcinoma-cell-lines-in-vitro
#20
Mohamed Mahmud, Adriana Piwoni, Nina Filipczak, Martyna Janicka, Jerzy Gubernator
The incorporation of hydrophobic drugs into liposomes improve their bioavailability and leads to increased stability and anticancer activity, along with decreased drug toxicity. Curcumin (Cur) is a natural polyphenol compound with a potent anticancer activity in pancreatic adenocarcinoma (PA). In the present study, different types of Cur-loaded liposomal formulations were prepared and characterized in terms of size, shape, zeta potential, optimal drug-to-lipid ratio and stability at 4°C, 37°C; and in human plasma in vitro...
2016: PloS One
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