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https://www.readbyqxmd.com/read/29667444/akt2-sirna-delivery-with-amphiphilic-based-polymeric-micelles-show-efficacy-against-cancer-stem-cells
#1
Diana Rafael, Petra Gener, Fernanda Andrade, Joaquin Seras-Franzoso, Sara Montero, Yolanda Fernández, Manuel Hidalgo, Diego Arango, Joan Sayós, Helena F Florindo, Ibane Abasolo, Simó Schwartz, Mafalda Videira
Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM)...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29667134/two-phase-i-pharmacokinetic-and-pharmacodynamic-studies-of-dfp-10917-a-novel-nucleoside-analog-with-14-day-and-7-day-continuous-infusion-schedules
#2
Kamalesh Sankhala, Chris H Takimoto, Alain C Mita, Henry Xiong, Jordi Rodón, Amir Mehrvarz Sarshekeh, K Burns, Kenzo Iizuka, Scott Kopetz
Purpose DFP-10917 is a novel deoxycytidine analog with a unique mechanism of action. Brief exposure to high concentrations of DFP-10917 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to DFP-10917 at low concentration causes DNA fragmentation, G2/M-phase arrest, and apoptosis. DFP-10917 demonstrated activity in tumor xenografts resistant to other deoxycytidine analogs. Experimental design Two phase I studies assessed the safety, pharmacokinetic, pharmacodynamic and preliminary efficacy of DFP-10917...
April 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29666783/development-of-neuroendocrine-prostate-cancers-by-the-ser-arg-repetitive-matrix-4-mediated-rna-splicing-network
#3
Ahn R Lee, Nicole Che, Jessica M Lovnicki, Xuesen Dong
While the use of next-generation androgen receptor pathway inhibition (ARPI) therapy has significantly increased the survival of patients with metastatic prostate adenocarcinoma (AdPC), several groups have reported a treatment-resistant mechanism, whereby cancer cells can become androgen receptor (AR) indifferent and gain a neuroendocrine (NE)-like phenotype. This subtype of castration-resistant prostate cancer has been termed "treatment-induced castration-resistant neuroendocrine prostate cancer" (CRPC-NE)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29666669/-egfr-amplification-induces-sensitivity-to-anti-egfr-therapy-in-pancreatic-acinar-cell-carcinoma
#4
Corentin Richard, Julie Niogret, Romain Boidot, Francois Ghiringhelli
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses...
April 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29666469/a-p53-mir-30a-zeb2-axis-controls-triple-negative-breast-cancer-aggressiveness
#5
Alessandra di Gennaro, Valentina Damiano, Giulia Brisotto, Michela Armellin, Tiziana Perin, Antonella Zucchetto, Michela Guardascione, Herman P Spaink, Claudio Doglioni, B Ewa Snaar-Jagalska, Manuela Santarosa, Roberta Maestro
Inactivation of p53 contributes significantly to the dismal prognosis of breast tumors, most notably triple-negative breast cancers (TNBCs). How the relief from p53 tumor suppressive functions results in tumor cell aggressive behavior is only partially elucidated. In an attempt to shed light on the implication of microRNAs in this context, we discovered a new signaling axis involving p53, miR-30a and ZEB2. By an in silico approach we identified miR-30a as a putative p53 target and observed that in breast tumors reduced miR-30a expression correlated with p53 inactivation, lymph node positivity and poor prognosis...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29666302/targeting-galectin-1-impairs-castration-resistant-prostate-cancer-progression-and-invasion
#6
Tsung-Chieh Shih, Ruiwu Liu, Chun-Te Wu, Xiaocen Li, Wenwu Xiao, Xiaojun Deng, Zsofia Kiss, Ting Wang, Xiaojia Chen, Randy P Carney, Hsing-Jien Kung, Yong Duan, Paramita M Ghosh, Kit S Lam
PURPOSE: The majority of prostate cancer (PCa) patients who are treated with androgen deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of Galectin-1 (Gal-1) is associated with PCa progression and poor clinical outcome. The role of Gal-1 in tumor progression are largely unknown. Here we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1inhibitor, LLS30, in mCRPC...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#7
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666142/tumor-xenograft-modeling-identifies-tcf4-itf2-loss-associated-with-breast-cancer-chemoresistance
#8
Gorka Ruiz de Garibay, Francesca Mateo, Agostina Stradella, Rafael Valdés-Mas, Luis Palomero, Jordi Serra-Musach, Diana A Puente, Ander Díaz-Navarro, Gardenia Vargas-Parra, Eva Tornero, Idoia Morilla, Lourdes Farré, María Martinez-Iniesta, Carmen Herranz, Emmet McCormack, August Vidal, Anna Petit, Teresa Soler, Conxi Lázaro, Xose S Puente, Alberto Villanueva, Miguel Angel Pujana
Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify loss of transcription factor 4 (TCF4) associated with this process. A triple-negative BRCA1 -mutated PDX was used to study the genetics of chemoresistance...
April 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29666038/correlation-of-serum-ccl3-mip-1%C3%AE-levels-with-disease-severity-in-postmenopausal-osteoporotic-females
#9
Hui Wan, Tie-Yong Qian, Xiao-Jing Hu, Ci-You Huang, Wei-Feng Yao
BACKGROUND: The pro-inflammatory protein chemokine cytokine ligand 3 is well-established as a vital regulator of bone resorption and osteoclasts stimulation. AIMS: We sought to investigate if serum chemokine cytokine ligand 3 levels correlated with disease severity in postmenopausal osteoporosis females. STUDY DESIGN: Cross-sectional Study. METHODS: 82 postmenopausal osteoporotic females, 76 postmenopausal non-osteoporotic women and 80 healthy female at childbearing age were recruited...
April 15, 2018: Balkan Medical Journal
https://www.readbyqxmd.com/read/29665939/-research-progress-of-%C3%AE-catenin-in-chronic-myelogenous-leukemia-review
#10
Wei Ding, Yu-Feng Li
β-catenin is an important member of Wnt signaling pathway. With more and more research on the relationship between β-catenin and cancers, it is noted that the concentration of β-catenin in cells is not only the landmark of activating the Wnt signaling pathway, but also a common phenomenon in various tumor cells. Moreover, abnormal expression of β-catenin is reported in blastic phase of CML and IM-resistant CML. Besides, β-catenin inhibitor is proved to be effective for the improvement of the IM susceptibility and the postponment of blastic phase...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665670/-the-relationship-between-the-radioresistance-of-pancreatic-cancer-cell-sw1990-and-the-induction-of-the-epithelial-mesenchymal-transition-an-in-vitro-study
#11
Y H Jiang, K Y You, Z F Bi, L T Li, H Q Mo, Y M Liu
Objective: To investigate the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of the Epithelial-Mesenchymal Transition (EMT). Methods: The radio-resistant pancreatic cancer cell SW1990-R were established by using the method of radiating pancreatic cancer cell SW1990 step by step and repeatedly. Then the changes of the morphology of the cell was observed by inverted phase contrast microscope, the radioresistance of SW1990-R was detected by colony-forming assay, and the apoptosis rate of the two cell lines after radiation were measured by flow cytometry...
March 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29665654/hypericin-affects-cancer-side-populations-via-competitive-inhibition-of-bcrp
#12
Jana Vargová, Jaromír Mikeš, Rastislav Jendželovský, Lucia Mikešová, Barbora Kuchárová, Ľubomír Čulka, Radek Fedr, Ján Remšík, Karel Souček, Alois Kozubík, Peter Fedoročko
OBJECTIVE: Cancer stem-like cells (CSLCs) are considered a root of tumorigenicity and resistance. However, their identification remains challenging. The use of the side population (SP) assay as a credible marker of CSLCs remains controversial. The SP assay relies on the elevated activity of ABC transporters that, in turn, can be modulated by hypericin (HYP), a photosensitizer and bioactive compound of St. John's Wort (Hypericum perforatum), a popular over-the-counter antidepressant. Here we aimed to comprehensively characterize the SP phenotype of cancer cells and to determine the impact of HYP on these cells...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29665649/subcellular-localization-of-klf4-in-non-small-cell-lung-cancer-and-its-clinical-significance
#13
Mingyue Liu, Xiqing Li, Ke-Zheng Peng, Tianhui Gao, Yao Cui, Ning Ma, Yun Zhou, Guiqin Hou
Kruppel-like factor 4 (Klf4) was reported to have both tumor suppressive and oncogenic roles on tumorigenesis, which is depend on its subcellular localization. In this study, the expression and subcellular localization of Klf4 in non-small cell lung cancer (NSCLC) patients as well as its clinical significance were analyzed, and the expression and subcellular localization of Klf4 in A549 cells and A549/DDP cells were detected. The results showed that the expression of Klf4 in nucleus was related to the histological grade and clinical stage of NSCLC patients...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29665526/novel-hydrazide-hydrazone-and-amide-substituted-coumarin-derivatives-synthesis-cytotoxicity-screening-microarray-radiolabeling-and-in-vivo-pharmacokinetic-studies
#14
Tamer Nasr, Samir Bondock, Hassan M Rashed, Walid Fayad, Mahmoud Youns, Tamer M Sakr
The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7...
April 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29665439/hyaluronic-acid-conjugated-nanoparticle-delivery-of-sirna-against-twist-reduces-tumor-burden-and-enhances-sensitivity-to-cisplatin-in-ovarian-cancer
#15
Sophia A Shahin, Ruining Wang, Shirleen I Simargi, Altagracia Contreras, Liliana Parra, Louise Qu, Wei Wen, Thanh Dellinger, Juli Unternaehrer, Fuyuhiko Tamanoi, Jeffrey I Zink, Carlotta A Glackin
TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses...
April 14, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29664658/downregulation-of-glut3-promotes-apoptosis-and-chemosensitivity-of-acute-myeloid-leukemia-cells-via-egfr-signaling
#16
Yan Zhuang, Jing Zhao, Xi Xu, Laixi Bi
BACKGROUND: Glucose transporter 3 (GLUT3) plays an important role in tumor progression and drug resistance in numerous malignancies, including acute myeloid leukemia (AML). However, the effect of GLUT3 silencing on treatment of AML remains poorly understood. The purpose of this study was to investigate role of GLUT3 in proliferation and chemosensitivity of AML and its underlying mechanisms. METHODS: The siRNA transfection was conducted using LipofectamineTM 2000...
February 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/29664570/what-if-protective-immunity-is-antigen-driven-and-not-due-to-so-called-memory-b-and-t-cells
#17
REVIEW
Rolf M Zinkernagel
Vaccines or early childhood exposure to infection mediate immunity, that is, improved resistance against disease and death caused by a second infection with the same agent. This has been explained by and equaled to immunological memory, that is, an "altered immune system behavior" that is maintained in a presumably antigen-independent fashion. This review summarizes epidemiological and experimental data, that largely falsify this idea and that show that periodic re-exposure to antigen either, artificially as vaccines or naturally as low-level persisting antigens or infections, or immune complexes on follicular dendritic cells or endemic re-exposure is necessary for protection...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664206/pedf-vegf-ratio-plays-a-crucial-role-in-the-spontaneous-regression-of-infant-hemangioma-and-the-therapeutic-effect-of-propranolol
#18
Liuqing Zhu, Jinye Xie, Zhenyin Liu, Zhijian Huang, Mao Huang, Haofan Yin, Weiwei Qi, Zhonghan Yang, Ti Zhou, Guoquan Gao, Jing Zhang, Xia Yang
Infantile hemangioma (IH) is a benign tumor that is formed by aberrant angiogenesis and that undergoes spontaneous regression over time. Propranolol, the first-line therapy for IH, inhibits angiogenesis by downregulating the activation of the VEGF pathway, which is hyperactivated in IH. However, this treatment is reportedly ineffective for 10% of tumors, and 19% of patients relapse after propranolol treatment. Both pro-angiogenic and anti-angiogenic factors regulate angiogenesis, and PEDF is the most effective endogenous anti-angiogenic factor...
April 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29664018/increased-vessel-perfusion-predicts-the-efficacy-of-immune-checkpoint-blockade
#19
Xichen Zheng, Zhaoxu Fang, Xiaomei Liu, Shengming Deng, Pei Zhou, Xuexiang Wang, Chenglin Zhang, Rongping Yin, Haitian Hu, Xiaolan Chen, Yijie Han, Yun Zhao, Steven H Lin, Songbing Qin, Xiaohua Wang, Betty Ys Kim, Penghui Zhou, Wen Jiang, Qingyu Wu, Yuhui Huang
Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#20
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
April 16, 2018: Journal of Clinical Investigation
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