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https://www.readbyqxmd.com/read/28550801/the-nk-1-receptor-antagonist-l-732-138-induces-apoptosis-in-human-gastrointestinal-cancer-cell-lines
#1
Miguel Muñoz, Marisa Rosso, Rafael Coveñas
BACKGROUND: Gastric and colon cancer cells express the neurokinin-1 receptor (NK-1R) and the peptide substance P (SP), after binding to this receptor, elicits the proliferation of gastrointestinal cancer cells and an antiapoptotic effect. In these cells, NK-1R antagonists (L-733,060: a piperidine derivative; aprepitant: a morpholine derivative) block, after binding to the NK-1R, the action of SP and exert an antiproliferative action, both antagonists promote apoptosis and the death of cancer cells...
February 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550283/high-resolution-bioelectrical-imaging-of-a%C3%AE-induced-network-dysfunction-on-cmos-meas-for-neurotoxicity-and-rescue-studies
#2
Hayder Amin, Thierry Nieus, Davide Lonardoni, Alessandro Maccione, Luca Berdondini
Neurotoxicity and the accumulation of extracellular amyloid-beta1-42 (Aβ) peptides are associated with the development of Alzheimer's disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28549792/endocannabinoids-modulate-apoptosis-in-endometriosis-and-adenomyosis
#3
Elif Bilgic, Elif Guzel Meydanli, Sevil Kose, Makbule Cisel Aydin, Eda Karaismailoglu, Irem Akar, Alp Usubutun, Petek Korkusuz
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues...
May 23, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#4
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28547977/the-association-of-tumor-lymphocyte-infiltration-with-clinicopathological-factors-and-survival-in-breast-cancer
#5
Joanna Huszno, Ewa Zembala Nożyńska, Dariusz Lange, Zofia Kołosza, Elżbieta Nowara
Recent studies have confirmed the role of tumor-infiltrating lymphocytes (TILs) in carcinogenesis and cancer progression. The aim of this study was to evaluate the correlation between the level of tumor lymphocyte infiltration and well-known clinicopathological factors in breast cancer patients. We also evaluated the influence of TILs on overall survival. Paraffin sections were retrospectively evaluated in 76 cases in early stage breast cancer patients who underwent surgery followed by systemic treatment. Tumor-infiltrating lymphocytes were classified as absent (grade 0), mild (grade 1), moderate (grade 2), or severe (grade 3)...
2017: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
https://www.readbyqxmd.com/read/28547656/influence-of-clinical-societal-and-treatment-variables-on-racial-differences-in-er-pr-breast-cancer-survival
#6
M E Roseland, K Schwartz, J J Ruterbusch, L Lamerato, R Krajenta, J Booza, Michael S Simon
BACKGROUND: African American (AA) women with breast cancer have persistently higher mortality compared to whites. We evaluated racial disparities in mortality among women with estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancer. METHODS: The study population included 542 women (45% AA) diagnosed with ER/PR-negative Stage I through III breast cancer treated at the Henry Ford Health System (HFHS) between 1996 and 2005. Linked datasets from HFHS, Metropolitan Detroit Cancer Surveillance System, and the U...
May 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28547157/shikonin-induces-necroptosis-by-reactive-oxygen-species-activation-in-nasopharyngeal-carcinoma-cell-line-cne-2z
#7
Zixuan Zhang, Zhirui Zhang, Qixiang Li, Hao Jiao, Dianlong Chong, Xiaojin Sun, Pei Zhang, Qiang Huo, Hao Liu
Shikonin, a natural small agent, has shown inhibitory effect in many kinds of cells, which increases intracellular reactive oxygen species (ROS) level and causes mitochondrial injury. In this study, shikonin showed good inhibitory effect on nasopharyngeal carcinoma CNE-2Z cells in vivo and vitro. The results presented here revealed that ROS levels increased markly after shikonin treated. The electron microscopy displays the change in ultrastructure of CNE-2Z cells after treatment for shikonin, which indicated that shikonin induced necroptosis...
May 25, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28546314/chronic-stress-induced-behavioral-changes-associated-with-subregion-selective-serotonin-cell-death-in-the-dorsal-raphe
#8
Reka Natarajan, Laura Forrester, Nicolas Chiaia, Bryan K Yamamoto
The current study examined the neurochemical mechanisms and neuroanatomical changes underlying co-existing behavioral effects associated with chronic stress-induced alterations in serotonin (5HT) neurons. Chronic unpredictable stress (CUS) to adult male rats produced depression-like changes with cognitive dysfunction and selective cell death in the interfascicular nucleus of the dorsal raphe (DRif) resulting in decreased 5HTergic innervation of medial prefrontal cortex (mPFC). Twenty-one days of CUS decreased basal plasma levels of corticosterone and produced a shorter latency to immobility and longer durations of immobility in the force-swim test that persisted for one month after CUS...
May 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#9
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#10
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545639/novel-diabetes-drugs-and-the-cardiovascular-specialist
#11
REVIEW
Naveed Sattar, Mark C Petrie, Bernard Zinman, James L Januzzi
Recently, treatment with 2 newer classes of type 2 diabetes drugs were found to reduce events in patients with diabetes and cardiovascular (CV) disease, a group common in cardiology clinics. The sodium-glucose cotransporter 2 inhibitor, empagliflozin, markedly and rapidly reduced CV death and heart failure hospitalization, likely with hemodynamic/metabolic-driven mechanisms of action. More recently, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide also reduced CV death and/or major adverse CV events, but did so more slowly and did not influence heart failure risks, suggesting alternative mechanisms of benefit...
May 30, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28545581/increased-serum-level-of-soluble-interleukin-2-receptor-is-associated-with-a-worse-response-of-metastatic-clear-cell-renal-cell-carcinoma-to-interferon-alpha-and-sequential-vegf-targeting-therapy
#12
Akinori Nukui, Akinori Masuda, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#13
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28545490/glutamate-signaling-through-the-nmda-receptor-reduces-the-expression-of-scleraxis-in-plantaris-tendon-derived-cells
#14
Christoph Spang, Ludvig J Backman, Sandrine Le Roux, Jialin Chen, Patrik Danielson
BACKGROUND: A body of evidence demonstrating changes to the glutaminergic system in tendinopathy has recently emerged. This hypothesis was further tested by studying the effects of glutamate on the tenocyte phenotype, and the impact of loading and exposure to glucocorticoids on the glutamate signaling machinery. METHODS: Plantaris tendon tissue and cultured plantaris tendon derived cells were immunohisto-/cytochemically stained for glutamate, N-Methyl-D-Aspartate receptor 1 (NMDAR1) and vesicular glutamate transporter 2 (VGluT2)...
May 25, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28544905/high-serum-levels-of-soluble-interleukin-2-receptor-sil2-r-interleukin-6-il-6-and-tumor-necrosis-factor-alpha-tnf-are-associated-with-adverse-clinical-features-and-predict-poor-outcome-in-diffuse-large-b-cell-lymphoma
#15
Ivan Dlouhy, Xavier Filella, Jordina Rovira, Laura Magnano, Alfredo Rivas-Delgado, Tycho Baumann, Alejandra Martínez-Trillos, Olga Balagué, Antonio Martínez, Blanca González-Farre, Kennosuke Karube, Eva Gine, Julio Delgado, Elías Campo, Armando López-Guillermo
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with heterogeneous outcomes. To improve accuracy of the international prognostic index score, new biological variables are being investigated. The aim of this study was to determine the prognostic significance of serum levels of different cytokines, namely soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF). We analyzed 197 de novo DLBCL patients (91 M/106 F; median age 66 years) treated with immunochemotherapy in a single institution...
May 17, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28544624/pyrimidine-containing-epidermal-growth-factor-receptor-kinase-inhibitors-synthesis-and-biological-evaluation
#16
Gaurav Joshi, Himanshu Nayyar, Sourav Kalra, Praveen Sharma, Anjana Munshi, Sandeep Singh, Raj Kumar
Structure based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nM to 3 μM. mRNA expression of EGFR downstream target genes i.e. twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μM) in lung, colon and breast cancer cell lines...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544524/increase-of-cells-expressing-pd-1-and-pd-l1-and-enhancement-of-ifn-%C3%AE-production-via-pd-1-pd-l1-blockade-in-bovine-mycoplasmosis
#17
Shinya Goto, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis...
May 24, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28544360/impairment-of-insulin-signalling-in-peripheral-tissue-fails-to-extend-murine-lifespan
#18
Troy L Merry, Doreen Kuhlow, Beate Laube, Doris Pöhlmann, Andreas F H Pfeiffer, C Ronald Kahn, Michael Ristow, Kim Zarse
Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals. Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non-neuronal tissues of adult mice on the lifespan. We induced hemizygous (PerIRKO(+/-) ) or homozygous (PerIRKO(-/-) ) disruption of the IR in peripheral tissue of 15-weeks-old mice using a tamoxifen-inducible Cre transgenic mouse with only peripheral tissue expression, and subsequently monitored glucose metabolism, insulin signalling and spontaneous death rates over 4 years...
May 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/28543858/survival-improvement-in-human-retinal-pigment-epithelial-cells-via-fas-receptor-targeting-by-mir-374a
#19
Nooshin Tasharrofi, Fatemeh Kouhkan, Masoud Soleimani, Zahra-Sheila Soheili, Mahboubeh Kabiri, Mohaddeseh Mahmoudi Saber, Farid Abedin Dorkoosh
Oxidative conditions of the eye could contribute to retinal cells loss through activating the Fas-L/Fas pathway. This phenomenon is one of the leading causes of some ocular diseases like age-related macular degeneration (AMD). By targeting proteins at their mRNA level, microRNAs (miRNAs) can regulate gene expression and cell function. The aim of the present study is to investigate Fas targeting by miR-374a and find whether it can inhibit Fas-mediated apoptosis in primary human retinal pigment epithelial (RPE) cells under oxidative stress...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543279/role-of-ampa-receptors-in-homocysteine-nmdar-induced-crosstalk-between-erk-and-p38-map-kinase
#20
Ranjana Poddar, Alexandria Chen, Lucas Winter, Sathyanarayanan Rajagopal, Surojit Paul
Homocysteine, a metabolite of the methionine cycle has been reported to play a role in neurotoxicity through activation of NMDAR-mediated signaling pathway. The proposed mechanisms associated with homocysteine-NMDAR induced neurotoxicity involve a unique signaling pathway that triggers a crosstalk between ERK and p38 MAPKs, where activation of p38 MAPK is downstream of and dependent on ERK MAPK. However, the molecular basis of the ERK MAPK mediated p38 MAPK activation is not understood. The current study investigates whether AMPARs play a role in facilitating the ERK MAPK mediated p38 MAPK activation...
May 24, 2017: Journal of Neurochemistry
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