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https://www.readbyqxmd.com/read/28646810/synergistic-anti-breast-cancer-effects-of-combined-treatment-with-oleuropein-and-doxorubicin-in-vivo
#1
Maha H Elamin, Abdelsalam B Elmahi, Maha H Daghestani, Ebtesam M Al-Olayan, Reem A Al-Ajmi, Afrah F Alkhuriji, Sherifa S Hamed, Manal F Elkhadragy
Context • Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies Objective • The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646744/systematic-biobanking-novel-imaging-techniques-and-advanced-molecular-analysis-for-precise-tumor-diagnosis-and-therapy-the-polish-mobit-project
#2
Jacek Niklinski, Adam Kretowski, Marcin Moniuszko, Joanna Reszec, Anna Michalska-Falkowska, Magdalena Niemira, Michal Ciborowski, Radoslaw Charkiewicz, Dorota Jurgilewicz, Miroslaw Kozlowski, Rodryg Ramlau, Cezary Piwkowski, Miroslaw Kwasniewski, Monika Kaczmarek, Andrzej Ciereszko, Tomasz Wasniewski, Robert Mroz, Wojciech Naumnik, Ewa Sierko, Magdalena Paczkowska, Joanna Kisluk, Anetta Sulewska, Adam Cybulski, Zenon Mariak, Boguslaw Kedra, Jacek Szamatowicz, Paweł Kurzawa, Lukasz Minarowski, Angelika Edyta Charkiewicz, Barbara Mroczko, Jolanta Malyszko, Christian Manegold, Lothar Pilz, Heike Allgayer, Mohammed L Abba, Hartmut Juhl, Frauke Koch
Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized...
June 21, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#3
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646542/reconstitution-of-low-density-lipoproteins-with-fatty-acids-for-the-targeted-delivery-of-drugs-into-cancer-cells
#4
Chunlei Zhu, Pallab Pradhan, Da Huo, Jiajia Xue, Song Shen, Krishnendu Roy, Younan Xia
Low-density lipoproteins (LDLs) represent a novel class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. Here we report a facile procedure for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts...
June 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#5
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#6
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646470/apobec3b-and-il-6-form-a-positive-feedback-loop-in-hepatocellular-carcinoma-cells
#7
Shuran Li, Xueyang Bao, Duowei Wang, Linjun You, Xianjing Li, Hongbao Yang, Jinsong Bian, Yun Wang, Yong Yang
APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3B and IL-6, and thereby promoted the prolonged non-resolving inflammation...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28646353/creb1-regulates-glucose-transport-of-glioma-cell-line-u87-by-targeting-glut1
#8
Jiaying Chen, Can Zhang, Yang Mi, Fuxue Chen, Dongshu Du
Glioma is stemmed from the glial cells in the brain, which is accounted for about 45% of all intracranial tumors. The characteristic of glioma is invasive growth, as well as there is no obvious boundary between normal brain tissue and glioma tissue, so it is difficult to resect completely with worst prognosis. The metabolism of glioma is following the Warburg effect. Previous researches have shown that GLUT1, as a glucose transporter carrier, affected the Warburg effect, but the molecular mechanism is not very clear...
June 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28646291/application-of-open-access-databases-to-determine-functional-connectivity-between-resveratrol-binding-protein-qr2-and-colorectal-carcinoma
#9
Barbara B Doonan, Evelien Schaafsma, John T Pinto, Joseph M Wu, Tze-Chen Hsieh
Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP)...
June 23, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28646235/over-expression-of-long-non-coding-rna-panda-promotes-hepatocellular-carcinoma-by-inhibiting-senescence-associated-inflammatory-factor-il8
#10
Chuanhui Peng, Wendi Hu, Xiaoyu Weng, Rongliang Tong, Shaobing Cheng, Chaofeng Ding, Heng Xiao, Zhen Lv, Haiyang Xie, Lin Zhou, Jian Wu, Shusen Zheng
It has been reported that long non-coding RNA PANDA was disregulated in varieties types of tumor, but its expression level and biological role in hepatocellular carcinoma (HCC) remains contradictory. We detected PANDA expression in two independent cohorts (48 HCC patients following liver transplantation and 84 HCC patients following liver resection), and found that PANDA was down-regulated in HCC. Thereafter we explored its function in cancer biology by inversing its low expression. Surprisingly, overexpression of PANDA promoted HCC proliferation and carcinogenesis in vitro and in vivo...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646232/inhibition-of-erk1-2-restores-gsk3%C3%AE-activity-and-protein-synthesis-levels-in-a-model-of-tuberous-sclerosis
#11
Rituraj Pal, Vitaliy V Bondar, Carolyn J Adamski, George G Rodney, Marco Sardiello
Tuberous sclerosis (TS) is a multi-organ autosomal dominant disorder that is best characterized by neurodevelopmental deficits and the presence of benign tumors. TS pathology is caused by mutations in tuberous sclerosis complex (TSC) genes and is associated with insulin resistance, decreased glycogen synthase kinase 3β (GSK3β) activity, activation of the mammalian target of rapamycin complex 1 (mTORC1), and subsequent increase in protein synthesis. Here, we show that extracellular signal-regulated kinases (ERK1/2) respond to insulin stimulation and integrate insulin signaling to phosphorylate and thus inactivate GSK3β, resulting in increased protein synthesis that is independent of Akt/mTORC1 activity...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646148/mir-15b-5p-resensitizes-colon-cancer-cells-to-5-fluorouracil-by-promoting-apoptosis-via-the-nf-%C3%AE%C2%BAb-xiap-axis
#12
Ci Zhao, Qi Zhao, Chunhui Zhang, Guangyu Wang, Yuanfei Yao, Xiaoyi Huang, Fei Zhan, Yuanyuan Zhu, Jiaqi Shi, Jianan Chen, Feihu Yan, Yanqiao Zhang
Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. As a key mediator of inflammation-induced cancer, miR-15b-5p enhances these therapeutic effects are mainly attributed to targeting of the NF-κB signaling pathway through negative regulation of NF-κB1 and one of its kinase complexes IKK-α...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#13
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646079/identification-of-flavin-containing-monooxygenase-5-fmo5-as-a-regulator-of-glucose-homeostasis-and-a-potential-sensor-of-gut-bacteria
#14
Flora Scott, Sandra G Gonzalez Malagon, Brett A O'Brien, Diede Fennema, Sunil Veeravalli, Clarissa R Coveney, Ian R Phillips, Elizabeth A Shephard
We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5(-/-) mice). In comparison with wild-type (WT) counterparts, Fmo5(-/-) mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#15
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#16
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#17
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#18
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645939/combined-btk-and-pi3k%C3%AE-inhibition-with-acalabrutinib-and-acp-319-improves-survival-and-tumor-control-in-cll-mouse-model
#19
Carsten U Niemann, Helena I Mora-Jensen, Eman L Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas- Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J Lannutti, Adrian Wiestner, Sarah E M Herman
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645738/human-germline-hedgehog-pathway-mutations-predispose-to-fatty-liver
#20
Maria J Guillen Sacoto, Ariel F Martinez, Yu Abe, Paul Kruszka, Karin Weiss, Joshua L Everson, Ramon Bataller, David E Kleiner, Jerrold M Ward, Kathleen K Sulik, Robert J Lipinski, Benjamin D Solomon, Maximilian Muenke
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations affecting this pathway. METHODS: Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD...
June 20, 2017: Journal of Hepatology
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