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https://www.readbyqxmd.com/read/29053396/embryonic-stem-cell-secreted-factors-decrease-invasiveness-of-triple-negative-breast-cancer-cells-through-regulome-modulation
#1
Elizabeth Tarasewicz, Robert S Oakes, Misael O Aviles, Joelle Straehla, Kathryn M Chilton, Joseph T Decker, Jia Wu, Lonnie D Shea, Jacqueline S Jeruss
Stem cell microenvironments decrease the invasiveness of cancer cells, and elucidating the mechanisms associated with disease regression could further the development of targeted therapies for aggressive cancer subtypes. To this end, we applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to investigate the reprogramming of triple-negative breast cancer (TNBC) cells in conditions that promoted a less aggressive phenotype. The repressive environment was established through exposure to mouse embryonic stem cell conditioned media (mESC CM)...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29053266/structure-activity-relationships-of-new-natural-product-based-diaryloxazoles-with-selective-activity-against-androgen-receptor-positive-breast-cancer-cells
#2
Andrew J Robles, Shelby McCowen, Shengxin Cai, Michaels Glassman, Francisco Ruiz, Robert H Cichewicz, Stanton F McHardy, Susan L Mooberry
Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC...
October 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29052961/amphiphilic-small-peptides-for-delivery-of-plasmid-dnas-and-sirnas
#3
Eun-Kyoung Bang, Hanna Cho, Sean S-H Jeon, Na Ly Tran, Dong-Kwon Lim, Wooyoung Hur, Taebo Sim
Although various delivery systems for nucleic acids have been reported, development of an efficient and non-toxic delivery carrier is still a key subject for gene therapy. In order to find new efficient delivery carriers for nucleic acids, we synthesized amphiphilic peptides composed of a guanidino group, an oleyl group, and a cysteine. We prepared both linear and branched types of peptides, and found that the linear peptides were superior to the branched peptides as nucleic acid carriers. Our study also suggested that the intermolecular cysteine disulfides might allow the linear peptides to form the optimal particle sizes with nucleic acids for cellular uptake...
October 20, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29052614/narp-mediates-antidepressant-like-effects-of-electroconvulsive-seizures
#4
Andrew D Chang, Punit V Vaidya, Edward P Retzbach, Sunho J Chung, Urian Kim, Kathryn Baselice, Kristen Maynard, Alec Stepanian, Melissa Staley, Lan Xiao, Ashley Blouin, Sungho Han, JongAh Lee, Paul F Worley, Kellie L Tamashiro, Barbara L Hempstead, Keri Martinowich, Mary Ann Wilson, Jay M Baraban, Irving M Reti
Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy...
October 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29052349/relationship-between-ugt1a1-27-and-ugt1a1-7-polymorphisms-and-irinotecan-related-toxicities-in-patients-with-lung-cancer
#5
Minoru Fukuda, Manabu Okumura, Tomomi Iwakiri, Kazuhiko Arimori, Takuya Honda, Kazuma Kobayashi, Hiroaki Senju, Shinnosuke Takemoto, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Nobuko Matsuo, Hiroshi Mukae, Kazuto Ashizawa
BACKGROUND: The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. METHODS: The eligibility criteria were: lung cancer patients scheduled to undergo irinotecan therapy, aged ≥ 20 years, with a performance status of 0-2. Thirty-one patients were enrolled and their blood was collected and used to examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy...
October 20, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29051371/adrenergic-nerves-activate-an-angio-metabolic-switch-in-prostate-cancer
#6
Ali H Zahalka, Anna Arnal-Estapé, Maria Maryanovich, Fumio Nakahara, Cristian D Cruz, Lydia W S Finley, Paul S Frenette
Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial β-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cell metabolism...
October 20, 2017: Science
https://www.readbyqxmd.com/read/29051118/sequential-therapy-with-redox-responsive-glucolipid-nanocarrier-separately-delivering-sirna-and-doxorubicin-to-overcome-multidrug-resistance
#7
Tingting Meng, Binbin Lu, Shihong Shao, Ming Yuan, Xuan Liu, Hong Yuan, Xuan Huang, Fuqiang Hu
P-glycoprotein (P-gp) is a major efflux transporter overexpressed on multidrug resistant tumor cells and responsible for pumping drugs out. If anti-tumor drugs are given when P-gp level is low, satisfactory treatment efficiency may be achieved. Thus, a P-gp down-regulating siRNA (siMDR1) and doxorubicin (DOX) were applied to eliminate multidrug resistant breast cancer cells (MCF-7/ADR). A redox-responsive glucolipid conjugate (CSO-ss-SA) was used to condense siRNA (CSO-ss-SA/siRNA) and encapsulate DOX (CSO-ss-SA/DOX) separately...
October 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29050982/pharmacological-inhibition-of-dusp6-suppresses-gastric-cancer-growth-and-metastasis-and-overcomes-cisplatin-resistance
#8
Qi-Nian Wu, Yi-Fu Liao, Yun-Xin Lu, Yun Wang, Jia-Huan Lu, Zhao-Lei Zeng, Qi-Tao Huang, Hui Sheng, Jing-Ping Yun, Dan Xie, Huai-Qiang Ju, Rui-Hua Xu
Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival...
October 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29050770/genomic-plasticity-between-human-and-mycobacterial-dna-a-review
#9
REVIEW
Lawal Danjuma, Mok Pooi Ling, Rukman Awang Hamat, Akon Higuchi, Abdullah A Alarfaj, Marlina, Giovanni Benelli, Palanisamy Arulselvan, Mariappan Rajan, Suresh Kumar Subbiah
Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29050694/the-biology-of-philadelphia-chromosome-like-all
#10
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050380/inflammasomes-in-neurological-diseases-emerging-pathogenic-and-therapeutic-concepts
#11
Manmeet K Mamik, Christopher Power
Inflammasome activation in the central nervous system occurs in both health and disease. Inflammasomes are cytosolic protein complexes that sense specific infectious or host stimuli and initiate inflammatory responses through caspase activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic cleavage and release of the pro-inflammatory cytokines, interleukin-1β and interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell death. Recent developments in the inflammasome field have uncovered novel molecular mechanisms that contribute to a broad range of neurological disorders including those associated with specific mutations in inflammasome genes as well as diseases modulated by inflammasome activation...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050366/the-resistance-mechanisms-and-treatment-strategies-for-egfr-mutant-advanced-non-small-cell-lung-cancer
#12
REVIEW
Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been established as the standard therapy for EGFR-sensitizing mutant advanced non-small-cell lung cancer (NSCLC). However, patients ultimately develop resistance to these drugs. There are several mechanisms of both primary and secondary resistance to EGFR-TKIs. The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#13
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050223/mir-23a-promotes-tgf-%C3%AE-1-induced-emt-and-tumor-metastasis-in-breast-cancer-cells-by-directly-targeting-cdh1-and-activating-wnt-%C3%AE-catenin-signaling
#14
Fei Ma, Wenjie Li, Chunxiao Liu, Wei Li, Haining Yu, Bo Lei, Yanlv Ren, Zhigao Li, Da Pang, Cheng Qian
TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050198/mtorc1-autophagy-regulated-mertk-in-mutant-brafv600-melanoma-with-acquired-resistance-to-braf-inhibition
#15
Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050003/cantharidin-inhibits-the-growth-of-triple-negative-breast-cancer-cells-by-suppressing-autophagy-and-inducing-apoptosis-in-vitro-and-in-vivo
#16
Hong-Chang Li, Zhi-Hua Xia, Ya-Feng Chen, Fan Yang, Wen Feng, Han Cai, Yi Mei, Yi-Ming Jiang, Ke Xu, Dian-Xu Feng
BACKGROUND/AIMS: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas), has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC) cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms. METHODS: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29049797/astrocyte-elevated-gene-1-is-overexpressed-in-non-small-cell-lung-cancer-and-associated-with-increased-tumour-angiogenesis
#17
Qiuping Ding, Yingrong Chen, Shunli Dong, Xuting Xu, Jin Liu, Pengtao Song, Caihua Yu, Zhihong Ma
OBJECTIVES: Astrocyte elevated gene-1 (AEG-1) functions to mediate angiogenesis, and its upregulation is responsible for tumour angiogenesis during cancer development. This study analysed AEG-1 expression in non-small-cell lung cancer (NSCLC) for association with NSCLC clinicopathological features and tumour angiogenesis. METHODS: The expression of AEG-1, vascular endothelial growth factor and intratumoural microvessel density (assessed using the expression of CD105) was detected by immunohistochemistry in 88 paired tumour tissue and adjacent normal tissue specimens obtained from NSCLC patients...
October 13, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29049738/a-genome-wide-scan-for-microrna-related-genetic-variants-associated-with-primary-open-angle-glaucoma
#18
Mohsen Ghanbari, Adriana I Iglesias, Henriët Springelkamp, Cornelia M van Duijn, M Arfan Ikram, Abbas Dehghan, Stefan J Erkeland, Caroline C W Klaver, Magda A Meester-Smoor
Purpose: To identify microRNAs (miRNAs) involved in primary open-angle glaucoma (POAG), using genetic data. MiRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Genetic variants in miRNAs or miRNA-binding sites within gene 3'-untranslated regions (3'UTRs) are expected to affect miRNA function and contribute to disease risk. Methods: Data from the recent genome-wide association studies on intraocular pressure, vertical cup-to-disc ratio (VCDR), cupa area and disc area were used to investigate the association of miRNAs with POAG endophenotypes...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29049728/surgically-induced-focal-retinal-detachment-does-not-cause-detectable-sd-oct-retinal-changes-in-normal-human-retina
#19
Kaitlin Kogachi, Jeremy D Wolfe, Amir H Kashani
Purpose: Induction of focal retinal detachment (RD) for subretinal delivery of stem cells and gene therapy is increasingly common. In order to determine if this procedure has an adverse impact on the retina, we use spectral-domain optical coherence tomography (SD-OCT) to evaluate the pre- and postoperative retinal anatomy of the incidentally detached normal retina surrounding large submacular hemorrhages (SMH) during surgical displacement procedures. Methods: Retrospective, observational study of human subjects with monocular SMH evaluated before and after surgical displacement using clinical exam, fundus photography, and SD-OCT...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29049475/potential-of-aqueous-humor-as-a-surrogate-tumor-biopsy-for-retinoblastoma
#20
Jesse L Berry, Liya Xu, A Linn Murphree, Subramanian Krishnan, Kevin Stachelek, Emily Zolfaghari, Kathleen McGovern, Thomas C Lee, Anders Carlsson, Peter Kuhn, Jonathan W Kim, David Cobrinik, James Hicks
Importance: Retinoblastoma (Rb) is one of the first tumors to have a known genetic etiology. However, because biopsy of this tumor is contraindicated, it has not been possible to define the effects of secondary genetic changes on the disease course. Objective: To investigate whether the aqueous humor (AH) of Rb eyes has sufficient tumor-derived DNA to perform genetic analysis of the tumor, including DNA copy number alterations. Design, Setting, and Participants: This investigation was a case series study at a tertiary care hospital (Children's Hospital Los Angeles) with a large Rb treatment center...
October 12, 2017: JAMA Ophthalmology
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