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https://www.readbyqxmd.com/read/28714590/adaptive-testing-for-association-between-two-random-vectors-in-moderate-to-high-dimensions
#1
Zhiyuan Xu, Gongjun Xu, Wei Pan
Testing for association between two random vectors is a common and important task in many fields, however, existing tests, such as Escoufier's RV test, are suitable only for low-dimensional data, not for high-dimensional data. In moderate to high dimensions, it is necessary to consider sparse signals, which are often expected with only a few, but not many, variables associated with each other. We generalize the RV test to moderate-to-high dimensions. The key idea is to data adaptively weight each variable pair based on its empirical association...
July 17, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28666734/a-novel-inhibitor-of-farnesyltransferase-with-a-zinc-site-recognition-moiety-and-a-farnesyl-group
#2
Ayumi Tanaka, Mohamed O Radwan, Akiyuki Hamasaki, Asumi Ejima, Emiko Obata, Ryoko Koga, Hiroshi Tateishi, Yoshinari Okamoto, Mikako Fujita, Mitsuyoshi Nakao, Kazuo Umezawa, Fuyuhiko Tamanoi, Masami Otsuka
Protein prenylation such as farnesylation and geranylgeranylation is associated with various diseases. Thus, many inhibitors of prenyltransferase have been developed. We report novel inhibitors of farnesyltransferase with a zinc-site recognition moiety and a farnesyl/dodecyl group. Molecular docking analysis showed that both parts of the inhibitor fit well into the catalytic domain of farnesyltransferase. The synthesized inhibitors showed activity against farnesyltransferase in vitro and inhibited proliferation of the pancreatic cell line AsPC-1...
June 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28652266/long-non-coding-rna-jhdm1d-as1-promotes-tumor-growth-by-regulating-angiogenesis-in-response-to-nutrient-starvation
#3
Ayano Kondo, Aya Nonaka, Teppei Shimamura, Shogo Yamamoto, Tetsuo Yoshida, Tatsuhiko Kodama, Hiroyuki Aburatani, Tsuyoshi Osawa
Long non-coding RNAs play a pivotal role in tumor progression, but their role in cancer cells in the nutrient-starved tumor microenvironment remains unknown. Here, we show that a nutrient starvation-responsive long non-coding RNA, JHDM1D antisense 1 (JHDM1D-AS1), promotes tumorigenesis by regulating angiogenesis in response to nutrient starvation. Expression of JHDM1D-AS1 was increased in cancer cells. In addition, expression of JHDM1D-AS1 was increased in clinical tumor samples compared to that in normal tissue...
June 26, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28645477/the-overexpression-of-cpr-and-p450-3a4-in-pancreatic-cancer-cells-changes-the-metabolic-profile-and-increases-the-cytotoxicity-and-pro-apoptotic-activity-of-acridine-antitumor-agent-c-1748
#4
Barbara Borowa-Mazgaj, Anna Mróz, Ewa Augustin, Ewa Paluszkiewicz, Zofia Mazerska
Drug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and AsPC-1, differing in expression levels of commonly mutated genes for this cancer type, to C-1748 treatment and (ii) the role of P450 3A4 isoenzyme and cytochrome P450 reductase (CPR) in the modulation of this response...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28618969/penfluridol-induces-endoplasmic-reticulum-stress-leading-to-autophagy-in-pancreatic-cancer
#5
Alok Ranjan, Nadezhda German, Constantinos Mikelis, Kalkunte Srivenugopal, Sanjay K Srivastava
Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28609101/design-synthesis-and-evaluation-of-thiazolidine-2-4-dione-derivatives-as-a-novel-class-of-glutaminase-inhibitors
#6
Teng-Kuang Yeh, Ching-Chuan Kuo, Yue-Zhi Lee, Yi-Yu Ke, Kuang-Feng Chu, Hsing-Yu Hsu, Hsin-Yu Chang, Yu-Wei Liu, Jen-Shin Song, Cheng-Wei Yang, Li-Mei Lin, Manwu Sun, Szu-Huei Wu, Po-Chu Kuo, Chuan Shih, Chiung-Tong Chen, Lun Kelvin Tsou, Shiow-Ju Lee
Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4-dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized...
June 29, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28607950/chemovirotherapy-of-pancreatic-adenocarcinoma-by-combining-oncolytic-vaccinia-virus-glv-1h68-with-nab-paclitaxel-plus-gemcitabine
#7
Eike Binz, Susanne Berchtold, Julia Beil, Martina Schell, Christine Geisler, Irina Smirnow, Ulrich M Lauer
Oncolytic viruses have proven their therapeutic potential against a variety of different tumor entities both in vitro and in vivo. Their ability to selectively infect and lyse tumor cells, while sparing healthy tissues, makes them favorable agents for tumor-specific treatment approaches. Particularly, the addition of virotherapeutics to already established chemotherapy protocols (so-called chemovirotherapy) is of major interest. Here we investigated the in vitro cytotoxic effect of the oncolytic vaccinia virus GLV-1h68 combined with dual chemotherapy with nab-paclitaxel plus gemcitabine in four human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, MIA-PaCa-2, and Panc-1)...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28599281/hif-2%C3%AE-promotes-the-formation-of-vasculogenic-mimicry-in-pancreatic-cancer-by-regulating-the-binding-of-twist1-to-the-ve-cadherin-promoter
#8
Jian Yang, Dong-Ming Zhu, Xiao-Gang Zhou, Ni Yin, Yi Zhang, Zi-Xiang Zhang, De-Chun Li, Jian Zhou
Vasculogenic mimicry (VM) is a blood supply modality that occurs independently of endothelial cell angiogenesis. Hypoxia and the epithelial-mesenchymal transition (EMT) induce VM formation by remodeling the extracellular matrix. Our previous study demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) promotes the progress of EMT in pancreatic cancer; however, whether HIF-2α promotes VM formation in pancreatic cancer remains unknown. In this study, we investigated HIF-2α expression and VM by immunohistochemistry in 70 pancreatic cancer patients as well as the role of Twist1and Twist2 in HIF-2α-induced VM in vitro and in vivo...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592083/-correlation-between-mir-1178-expression-and-clinicopathological-significance-in-human-pancreatic-cancer
#9
Z Cao, S L Zheng, G Yang, M Y Feng, L F Zheng, T P Zhang, Y P Zhao
Objective: To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism. Methods: The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion...
June 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28576633/design-synthesis-and-biological-evaluation-of-sulfonamide-substituted-diphenylpyrimidine-derivatives-sul-dppys-as-potent-focal-adhesion-kinase-fak-inhibitors-with-antitumor-activity
#10
Menghua Qu, Zhihao Liu, Dan Zhao, Changyuan Wang, Jianbin Zhang, Zeyao Tang, Kexin Liu, Xiaohong Shu, Hong Yuan, Xiaodong Ma
A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10µM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells)...
May 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28549346/functional-heterogeneity-in-tumor-derived-human-pancreatic-stellate-cells-differential-expression-of-hgf-and-implications-for-mitogenic-signaling-and-migration-in-pancreatic-cancer-cells
#11
Vegard Tjomsland, Monica Aasrum, Thoralf Christoffersen, Ivar P Gladhaug
The pancreatic stellate cell (PSC) is the principal cell type of the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC). PSCs interact with cancer cells and influence the progression of the disease through a complex network of signaling molecules including hepatocyte growth factor (HGF). Functional heterogeneity of PSCs within a tumor might conceivably influence tumor progression. We investigated PSC populations isolated from different human PDACs and examined the effects of PSC-conditioned medium on BxPC-3 and AsPC-1 pancreatic cancer cells...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476028/hif-2%C3%AE-dictates-the-susceptibility-of-pancreatic-cancer-cells-to-trail-by-regulating-survivin-expression
#12
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...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430580/expression-status-of-folate-receptor-alpha-is-a-predictor-of-survival-in-pancreatic-ductal-adenocarcinoma
#13
Lei Cai, Theodoros Michelakos, Cristina R Ferrone, Liyuan Zhang, Vikram Deshpande, Qi Shen, Albert DeLeo, 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...
June 6, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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