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https://www.readbyqxmd.com/read/28328015/pcsk9-inhibitor-access-barriers-issues-and-recommendations-improving-the-access-process-for-patients-clinicians-and-payers
#1
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...
March 22, 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
#2
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
#3
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)...
February 8, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27917791/investigation-of-the-expression-of-rif1-gene-on-head-and-neck-pancreatic-and-brain-cancer-and-cancer-stem-cells
#13
Hacer E GursesCila, Muradiye Acar, Furkan B Barut, Mehmet Gunduz, Reidar Grenman, Esra Gunduz
PURPOSE: Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. METHODS: UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#14
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27889645/suppression-of-tumor-growth-and-muscle-wasting-in-a-transgenic-mouse-model-of-pancreatic-cancer-by-the-novel-histone-deacetylase-inhibitor-ar-42
#15
Sally E Henderson, Li-Yun Ding, Xiaokui Mo, Tanios Bekaii-Saab, Samuel K Kulp, Ching-Shih Chen, Po-Hsien Huang
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. This study was aimed at evaluating the efficacy of AR-42 (formerly OSU-HDAC42), a novel histone deacetylase (HDAC) inhibitor currently in clinical trials, in suppressing tumor growth and/or cancer-induced muscle wasting in murine models of PDAC. EXPERIMENTAL DESIGN: The in vitro antiproliferative activity of AR-42 was evaluated in six human pancreatic cancer cell lines (AsPC-1, COLO-357, PANC-1, MiaPaCa-2, BxPC-3, SW1990)...
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27888805/effects-of-abies-sibirica-terpenes-on-cancer-and-aging-associated-pathways-in-human-cells
#16
Anna Kudryavtseva, George Krasnov, Anastasiya Lipatova, Boris Alekseev, Faniya Maganova, Mikhail Shaposhnikov, Maria Fedorova, Anastasiya Snezhkina, Alexey Moskalev
A large number of terpenoids exhibit potential geroprotector and anti-cancer properties. Here, we studied whole transcriptomic effects of Abisil, the extract of fir (Abies sibirica) terpenes, on normal and cancer cell lines. We used early passaged and senescent none-immortalized fibroblasts as cellular aging models. It was revealed that in normal fibroblasts, terpenes induced genes of stress response, apoptosis regulation and tissue regeneration. The restoration of the expression level of some prolongevity genes after fir extract treatment was shown in old cells...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884119/anti-lrp-lr-specific-antibody-igg1-is18-impedes-adhesion-and-invasion-of-pancreatic-cancer-and-neuroblastoma-cells
#17
Thalia M Rebelo, Carryn J Chetty, Eloise Ferreira, Stefan F T Weiss
BACKGROUND: Cancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps...
November 24, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27876069/mgdg-extracted-from-spinach-enhances-the-cytotoxicity-of-radiation-in-pancreatic-cancer-cells
#18
Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki
BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. METHODS: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs)...
November 22, 2016: Radiation Oncology
https://www.readbyqxmd.com/read/27813236/peg-grafted-nanodiamonds-for-the-delivery-of-gemcitabine
#19
Mingxia Lu, Yu-Kai Wang, Jiacheng Zhao, Hongxu Lu, Martina H Stenzel, Pu Xiao
Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem)...
December 2016: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/27793935/antitumor-effects-of-eribulin-mesylate-in-gemcitabine-resistant-pancreatic-cancer-cell-lines
#20
Yuka Takezaki, Tsutomu Namikawa, Tsuyoshi Koyama, Eri Munekage, Masaya Munekage, Hiromichi Maeda, Hiroyuki Kitagawa, Kazuhiro Hanazaki
BACKGROUND/AIM: One reason of poor survival rate of patients with pancreatic cancer is the development of chemoresistance. The aim of the present study was to investigate the effects of eribulin mesylate in gemcitabine-refractory advanced pancreatic cancer cell lines. MATERIALS AND METHODS: Three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate...
2016: Anticancer Research
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