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https://www.readbyqxmd.com/read/28427237/oxidative-dna-double-strand-breaks-and-autophagy-in-the-antitumor-effect-of-sterically-hindered-platinum-ii-complexes-in-nsclcs
#1
Feihong Chen, Xinyi Wang, Xiufeng Jin, Jian Zhao, Shaohua Gou
A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427229/nadph-accumulation-is-responsible-for-apoptosis-in-breast-cancer-cells-induced-by-fatty-acid-synthase-inhibition
#2
Yanfen Cui, Pan Xing, Yuanyuan Wang, Miao Liu, Li Qiu, Guoguang Ying, Binghui Li
Fatty acid synthase (FAS), as a key enzyme involved in de novo lipogenesis, is highly expressed in many cancers. FAS inhibition induces cell death in vivo and in vitro, rendering FAS as an attractive target for cancer therapy, but the defined mechanism is still not well understood. Herein, we confirmed that FAS was highly expressed in breast cancers and FAS inhibition by its inhibitors or knockdown induced apoptosis in breast cancer cells. Our results showed that a significantly high level of reactive oxygen species was induced but not responsible for apoptosis in breast cancer cells by FAS inhibition...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427210/dependence-of-p53-deficient-cells-on-the-dhx9-dexh-box-helicase
#3
Teresa Lee, Jerry Pelletier
DHX9 is a DExH-box helicase family member with key regulatory roles in a broad range of cellular processes. It participates at multiple levels of gene regulation, including DNA replication, transcription, translation, RNA transport, and microRNA processing. It has been implicated in tumorigenesis and recent evidence suggests that it may be a promising chemotherapeutic target. Previous studies have determined that DHX9 suppression elicits an apoptotic or senescence response by activating p53 signaling. Here, we show that DHX9 inhibition can also have deleterious effects in cells lacking functional p53...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#4
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427156/the-effects-of-dleu1-gene-expression-in-burkitt-lymphoma-bl-potential-mechanism-of-chemoimmunotherapy-resistance-in-bl
#5
Sanghoon Lee, Wen Luo, Tishi Shah, Changhong Yin, Timmy O'Connell, Tae-Hoon Chung, Sherrie L Perkins, Rodney R Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella van de Ven, Mitchell S Cairo
Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427148/in-depth-proteomic-profiling-of-left-ventricular-tissues-in-human-end-stage-dilated-cardiomyopathy
#6
Shanshan Liu, Yan Xia, Xiaohui Liu, Yi Wang, Zhangwei Chen, Juanjuan Xie, Juying Qian, Huali Shen, Pengyuan Yang
Dilated cardiomyopathy (DCM) is caused by reduced left ventricular (LV) myocardial function, which is one of the most common causes of heart failure (HF). We performed iTRAQ-coupled 2D-LC-MS/MS to profile the cardiac proteome of LV tissues from healthy controls and patients with end-stage DCM. We identified 4263 proteins, of which 125 were differentially expressed in DCM tissues compared to LV controls. The majority of these were membrane proteins related to cellular junctions and neuronal metabolism. In addition, these proteins were involved in membrane organization, mitochondrial organization, translation, protein transport, and cell death process...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427089/editor-s-highlight-exposure-to-crvi-during-early-pregnancy-increases-oxidative-stress-and-disrupts-the-expression-of-antioxidant-proteins-in-placental-compartments
#7
Sakhila K Banu, Jone A Stanley, Kirthiram K Sivakumar, Robert J Taylor, Joe A Arosh, Robert C Burghardt
Epidemiologic studies document relationships between chromium VI (CrVI) exposure and increased risk of spontaneous abortion, stillbirth, preterm birth, and neonatal death in pregnant women. Environmental contamination with CrVI is a growing problem both in the United States and developing countries. CrVI is widely used in numerous industries. This study was designed to understand the mechanism of CrVI toxicity on placental oxidative stress and antioxidant (AOX) machinery. Pregnant mother rats were treated with or without CrVI (50 ppm K2Cr2O7) through drinking water from gestational day (GD) 9...
February 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28427061/emerging-insights-into-pathogenesis
#8
Edoardo Midena, Elisabetta Pilotto
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM). Persistent hyperglycemia leads to the activation of multiple cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction. DR has been considered a "chronic, low-grade inflammatory disease of the retina". However, an increasing body of evidence suggests that inflammation and neurodegeneration both occur in human diabetes even before the development of clinical signs of DR...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28426995/antibacterial-activity-of-n-methylbenzofuro-3-2-b-quinoline-and-n-methylbenzoindolo-3-2-b-quinoline-derivatives-and-study-of-their-mode-of-action
#9
Ning Sun, Ruo-Lan Du, Yuan-Yuan Zheng, Bao-Hua Huang, Qi Guo, Rui-Fang Zhang, Kwok-Yin Wong, Yu-Jing Lu
The emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Targeting at the inhibition of bacterial cell division via the control of FtsZ function is one of the effective and promising approaches. Some natural extracts from plants such as sanguinarine and berberine (analogs of pyridinium compounds) are known to alter FtsZ function. In this study, a series of novel quaternary pyridinium compounds was constructed based on the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and their antibacterial activity against nine significant pathogens was investigated using broth microdilution method...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28426875/bisphenol-a-activates-egfr-and-erk-promoting-proliferation-tumor-spheroid-formation-and-resistance-to-egfr-pathway-inhibition-in-estrogen-receptor-negative-inflammatory-breast-cancer-cells
#10
Scott J Sauer, Michael Tarpley, Imran Shah, Akshay V Save, H Kim Lyerly, Steven R Patierno, Kevin P Williams, Gayathri R Devi
Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28426838/a-second-wave-of-salmonella-t3ss1-activity-prolongs-the-lifespan-of-infected-epithelial-cells
#11
Ciaran E Finn, Audrey Chong, Kendal G Cooper, Tregei Starr, Olivia Steele-Mortimer
Type III secretion system 1 (T3SS1) is used by the enteropathogen Salmonella enterica serovar Typhimurium to establish infection in the gut. Effector proteins translocated by this system across the plasma membrane facilitate invasion of intestinal epithelial cells. One such effector, the inositol phosphatase SopB, contributes to invasion and mediates activation of the pro-survival kinase Akt. Following internalization, some bacteria escape from the Salmonella-containing vacuole into the cytosol and there is evidence suggesting that T3SS1 is expressed in this subpopulation...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426808/a-screen-for-protective-drugs-against-delayed-hypoxic-injury
#12
Chun-Ling Sun, Huiliang Zhang, Meng Liu, Wang Wang, C Michael Crowder
Despite longstanding efforts to develop cytoprotective drugs against ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to treat hypoxic injury. The failure of traditional strategies at solving this problem suggests the need for novel and unbiased approaches that can lead to previously unsuspected targets and lead compounds. Towards this end, we report here a unique small molecule screen in the nematode C. elegans for compounds that improve recovery when applied after the hypoxic insult, using a C...
2017: PloS One
https://www.readbyqxmd.com/read/28426338/causes-of-death-in-long-term-lung-cancer-survivors-a-seer-database-analysis
#13
Omar Abdel-Rahman
BACKGROUND: Long-term (>5 years) lung cancer survivors represent a small but distinct subgroup of lung cancer patients and information about the causes of death of this subgroup is scarce. METHODS: Surveillance, epidemiology and end results (SEER) database (1988-2008) has been utilized to determine the causes of death of long-term survivors of lung cancer. Survival analysis has been conducted through Kaplan Meier analysis and multivariate analysis has been conducted through a Cox proportional hazard model...
April 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28426244/piperine-triggers-apoptosis-of-human-oral-squamous-carcinoma-through-cell-cycle-arrest-and-mitochondrial-oxidative-stress
#14
Sahabjada Siddiqui, Md Sultan Ahamad, Asif Jafri, Mohd Afzal, Md Arshad
Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine...
April 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28426137/hydroxyurea-hydroxycarbamide-for-sickle-cell-disease
#15
REVIEW
Sarah J Nevitt, Ashley P Jones, Jo Howard
BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting...
April 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28425987/biological-activity-of-tumor-treating-fields-in-preclinical-glioma-models
#16
Manuela Silginer, Michael Weller, Roger Stupp, Patrick Roth
Glioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425986/p16ink4a-upregulation-mediated-by-tbk1-induces-retinal-ganglion-cell-senescence-in-ischemic-injury
#17
L U Li, Yin Zhao, Hong Zhang
Glaucoma is a leading cause of irreversible blindness worldwide that is characterized by progressive retinal ganglion cell (RGC) death. However, RGC senescence as a phase before RGC death, and the mechanism of RGC senescence remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model. Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16) expression and RGC senescence. Upregulation of TBK1 via plasmid transfection increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425936/genistein-ameliorates-ischemia-reperfusion-induced-renal-injury-in-a-sirt1-dependent-manner
#18
Wei-Fang Li, Kang Yang, Ping Zhu, Hong-Qian Zhao, Yin-Hong Song, Kuan-Can Liu, Wei-Feng Huang
Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation in clinical practice. Genistein, the main isoflavone found in soy products, is known to possess a wide spectrum of biochemical and pharmacological activities. However, the protective effect of genistein on renal I/R injury has not been well investigated. In the current study, we explore whether genistein exhibits its renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We found the treatment of genistein significantly reduced renal I/R-induced cell death, simultaneously stimulating renal cell proliferation...
April 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28425934/evaluation-of-the-effects-of-airborne-particulate-matter-on-bone-marrow-mesenchymal-stem-cells-bm-mscs-cellular-molecular-and-systems-biological-approaches
#19
Muhammad Abu-Elmagd, Mansour A Alghamdi, Magdy Shamy, Mamdouh I Khoder, Max Costa, Mourad Assidi, Roaa Kadam, Haneen Alsehli, Mamdooh Gari, Peter Natesan Pushparaj, Gauthaman Kalamegam, Mohammed H Al-Qahtani
Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2...
April 20, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28425586/introduction-to-nobel-conference-the-cell-cycle-and-cell-death-in-disease
#20
K G Wiman, B Zhivotovsky
No abstract text is available yet for this article.
May 2017: Journal of Internal Medicine
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