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https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#1
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211669/3-aminomethyl-derivatives-of-2-phenylimidazo-1-2-a-pyridine-as-positive-allosteric-modulators-of-gabaa-receptor-with-potential-antipsychotic-activity
#2
Monika Marcinkowska, Marcin Kolaczkowski, Krzysztof Kamiński, Adam Bucki, Maciej Henryk Pawlowski, Agata Siwek, Tadeusz Karcz, Gabriela Starowicz, Karolina Sloczynska, Elżbieta Pękala, Anna Wesołowska, Jerzy Samochowiec, Paweł Mierzejewski, Przemyslaw Bienkowski
Schizophrenia is a mental illness characterized by behavioral changes as well as anatomical and neurochemical abnormalities. There has been a remarkable progress in the drug discovery for schizophrenia; however, antipsychotics that act through molecular targets, other than monoaminergic receptors, have not been developed. One of the hypotheses of schizophrenia states that GABAergic dysfunction might be implemented in the pathophysiology of this disease. Our recent findings and previous clinical observations have suggested that modulation of GABAergic system through α1-GABAA receptors would represent an original approach for the treatment of schizophrenia...
February 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28211642/biomechanical-strain-exacerbates-inflammation-on-a-progeria-on-a-chip-model
#3
João Ribas, Yu Shrike Zhang, Patrícia R Pitrez, Jeroen Leijten, Mario Miscuglio, Jeroen Rouwkema, Mehmet Remzi Dokmeci, Xavier Nissan, Lino Ferreira, Ali Khademhosseini
Organ-on-a-chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues...
February 17, 2017: Small
https://www.readbyqxmd.com/read/28210286/bilastine-in-allergic-rhinoconjunctivitis-and-urticaria-a-practical-approach-to-treatment-decisions-based-on-queries-received-by-the-medical-information-department
#4
REVIEW
Amalia Leceta, Ander Sologuren, Román Valiente, Cristina Campo, Luis Labeaga
BACKGROUND: Bilastine is a safe and effective commonly prescribed non-sedating H1-antihistamine approved for symptomatic treatment in patients with allergic disorders such as rhinoconjunctivitis and urticaria. It was evaluated in many patients throughout the clinical development required for its approval, but clinical trials generally exclude many patients who will benefit in everyday clinical practice (especially those with coexisting diseases and/or being treated with concomitant drugs)...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28208916/delirium-in-parkinson-s-disease-a-cocktail-diagnosis
#5
Robin George Manappallil
Mental disturbances have been described in patients with Parkinson's Disease (PD). Of these, the common conditions are delirium and psychosis. Delirium has been attributed to change of environment, especially hospital stay and infections; while psychosis is due to drugs like dopamine agonists. This is a case of a 75-year-old male, on levodopa therapy for PD, who presented with delirium and ended up with a cocktail diagnosis: Cryptococcal meningitis, Hashimoto's Encephalopathy (HE), Urinary tract infection with acute renal failure, Uremic encephalopathy and Levodopa induced psychosis...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208696/valproate-attenuates-endoplasmic-reticulum-stress-induced-apoptosis-in-sh-sy5y-cells-via-the-akt-gsk3%C3%AE-signaling-pathway
#6
Zhengmao Li, Fenzan Wu, Xie Zhang, Yi Chai, Daqing Chen, Yuetao Yang, Kebin Xu, Jiayu Yin, Rui Li, Hongxue Shi, Zhouguang Wang, Xiaokun Li, Jian Xiao, Hongyu Zhang
Endoplasmic reticulum (ER) stress-induced apoptosis plays an important role in a range of neurological disorders, such as neurodegenerative diseases, spinal cord injury, and diabetic neuropathy. Valproate (VPA), a typical antiepileptic drug, is commonly used in the treatment of bipolar disorder and epilepsy. Recently, VPA has been reported to exert neurotrophic effects and promote neurite outgrowth, but its molecular mechanism is still unclear. In the present study, we investigated whether VPA inhibited ER stress and promoted neuroprotection and neuronal restoration in SH-SY5Y cells and in primary rat cortical neurons, respectively, upon exposure to thapsigargin (TG)...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207427/progression-and-characterization-of-the-accelerated-atherosclerosis-in-iliac-artery-of-new-zealand-white-rabbits-effect-of-simvastatin
#7
Jitendra S Kanshana, Vivek Khanna, Vishal Singh, Manish Jain, Ankita Misra, Sachin Kumar, Mariya Farooqui, Manoj K Barthwal, Madhu Dikshit
OBJECTIVE: Although atherosclerosis is described in New Zealand White rabbit's iliac artery, yet details of time-dependent atherosclerosis progression are not well known. Further, a well characterized accelerated model of atherosclerosis is also required for the screening of candidate drugs to target specific steps of atherosclerosis development. The present study extensively characterizes the time-dependent plaque composition and functional responses of the atherosclerosis in rabbit iliac artery and its modification by simvastatin...
February 14, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#8
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205568/luman-contributes-to-brefeldin-a-induced-prion-protein-gene-expression-by-interacting-with-the-erse26-element
#9
Marc-André Déry, Andréa C LeBlanc
The cellular prion protein (PrP) is essential for transmissible prion diseases, but its exact physiological function remains unclear. Better understanding the regulation of the human prion protein gene (PRNP) expression can provide insight into this elusive function. Spliced XBP1 (sXBP1) was recently shown to mediate endoplasmic reticulum (ER) stress-induced PRNP expression. In this manuscript, we identify Luman, a ubiquitous, non-canonical unfolded protein response (UPR), as a novel regulator of ER stress-induced PRNP expression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205547/microrna-17-family-promotes-polycystic-kidney-disease-progression-through-modulation-of-mitochondrial-metabolism
#10
Sachin Hajarnis, Ronak Lakhia, Matanel Yheskel, Darren Williams, Mehran Sorourian, Xueqing Liu, Karam Aboudehen, Shanrong Zhang, Kara Kersjes, Ryan Galasso, Jian Li, Vivek Kaimal, Steven Lockton, Scott Davis, Andrea Flaten, Joshua A Johnson, William L Holland, Christine M Kusminski, Philipp E Scherer, Peter C Harris, Marie Trudel, Darren P Wallace, Peter Igarashi, Edmund C Lee, John R Androsavich, Vishal Patel
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of renal failure. Here we identify miR-17 as a target for the treatment of ADPKD. We report that miR-17 is induced in kidney cysts of mouse and human ADPKD. Genetic deletion of the miR-17∼92 cluster inhibits cyst proliferation and PKD progression in four orthologous, including two long-lived, mouse models of ADPKD. Anti-miR-17 treatment attenuates cyst growth in short-term and long-term PKD mouse models. miR-17 inhibition also suppresses proliferation and cyst growth of primary ADPKD cysts cultures derived from multiple human donors...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205262/modern-multiple-myeloma-therapy-deep-sustained-treatment-response-and-good-clinical-outcomes
#11
REVIEW
O Landgren, K Iskander
In the USA at the beginning of this century, the average overall survival in patients with multiple myeloma was about 3 years. Around that time, three drugs (bortezomib, lenalidomide and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approval by the US Food and Drug Administration (FDA). Driven by access to better drugs, median overall survival in younger patients (aged <50 years) was >10 years by 2014. The FDA approved 14 new drugs for the treatment of cancer in 2015; four of these were approved for the treatment of myeloma (panobinostat, daratumumab, elotuzumab and ixazomib)...
February 16, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28205224/muc13-overexpression-in-renal-cell-carcinoma-plays-a-central-role-in-tumour-progression-and-drug-resistance
#12
Yonghua Sheng, Choa Ping Ng, Rohan Lourie, Esha T Shah, Yaowu He, Kuan Yau Wong, Inge Seim, Iulia Oancea, Christudas Morais, Penny L Jeffery, John Hooper, Glenda C Gobe, Michael A McGuckin
Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28204893/gastrointestinal-system-manifestations-in-juvenile-systemic-lupus-erythematosus
#13
Hafize Emine Sönmez, Asuman Nur Karhan, Ezgi Deniz Batu, Yelda Bilginer, Ersin Gümüş, Hülya Demir, Aysel Yüce, Seza Özen
Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68...
February 16, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28204845/mirnas-target-databases-developmental-methods-and-target-identification-techniques-with-functional-annotations
#14
REVIEW
Nagendra Kumar Singh
PURPOSE: microRNA (miRNA) regulates diverse biological mechanisms and metabolisms in plants and animals. Thus, the discoveries of miRNA has revolutionized the life sciences and medical research.The miRNA represses and cleaves the targeted mRNA by binding perfect or near perfect or imperfect complementary base pairs by RNA-induced silencing complex (RISC) formation during biogenesis process. One miRNA interacts with one or more mRNA genes and vice versa, hence takes part in causing various diseases...
February 15, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28203577/ertapenem-induced-encephalopathy-in-a-patient-with-normal-renal-function
#15
S Scott Sutton, Mark Jumper, Sean Cook, Babatunde Edun, Michael D Wyatt
Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient's symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28203563/unsuccessful-treatment-with-abatacept-in-recurrent-focal-segmental-glomerulosclerosis-after-kidney-transplantation
#16
Tilde Kristensen, Per Ivarsen, Johan Vestergaard Povlsen
Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation occurs in up to 20-50% of FSGS patients and is associated with inferior allograft survival. Treatment of both primary FSGS as well as recurrent FSGS after transplantation with plasma exchange and immunosuppression is often unsuccessful and remains a major challenge as the disease still leads to end-stage renal disease and decreased graft survival. Previous case reports have described patients with recurrent FSGS who were successfully treated with a B7-1 inhibitor (abatacept) inducing partial or complete remission...
January 2017: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/28203489/effects-of-anti-repulsive-guidance-molecule-c-rgmc-hemojuvelin-antibody-on-hepcidin-and-iron-in-mouse-liver-and-tumor-xenografts
#17
S V Torti, E Lemler, B K Mueller, A Popp, F M Torti
OBJECTIVE: Hepcidin is a peptide hormone produced by the liver that regulates systemic iron homeostasis. Hepcidin is also synthesized by tumors, where it contributes to tumor growth by increasing the tumoral retention of iron. Targeted reduction of hepcidin may therefore be useful in reducing tumor growth. H5F9-AM8 is an antibody in preclinical development for the anemia of chronic disease that reduces hepcidin synthesis by binding to RGMc, a co-receptor involved in the transcriptional induction of hepcidin by BMP6...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28202509/sodium-channel-subunit-scnn1b-suppresses-gastric-cancer-growth-and-metastasis-via-grp78-degradation
#18
Jun Yu, Qian Yun, Chi Chun Wong, Jiaying Xu, Huarong Chen, Yanquan Zhang, Wei Kang, Hua Wang, Li Zhang, Weilin Li, Eagle Sh Chu, Minnie Yy Go, Philip Wy Chiu, Enders Kw Ng, Francis Kl Chan, Joseph Jy Sung, Jianmin Si
There remains a paucity of functional biomarkers in gastric cancer. Here we report the identification of the sodium channel subunit SCNN1B as a candidate biomarker in gastric cancer (GC). SCNN1B mRNA expression was silenced commonly by promoter hypermethylation in GC cell lines and primary tumor tissues. Tissue microarray analysis revealed that high expression of SCNN1B was an independent prognostic factor for longer survival in GC patients, especially those with late-stage disease. Functional studies demonstrated that SCNN1B overexpression was sufficient to suppress multiple features of cancer cell pathophysiology in vitro and in vivo...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202387/varenicline-enhances-oxidized-ldl-uptake-by-increasing-expression-of-lox-1-and-cd36-scavenger-receptors-through-%C3%AE-7-nachr-in-macrophages
#19
Yuki Kanaoka, Mitsuhisa Koga, Keita Sugiyama, Kaoru Ohishi, Yasufumi Kataoka, Atsushi Yamauchi
Varenicline is a widely used and effective drug for smoking cessation. It is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and full agonist of α7 nAChR. We have reported that varenicline aggravates formation of atherosclerotic plaques through α7 nAChR in apolipoprotein E knockout mice. However, little is known about its effects on macrophages in atherosclerotic plaques. Here, we ascertained whether varenicline promotes oxidized low-density lipoprotein (oxLDL) uptake in mouse peritoneal macrophages in vitro and clarified its mechanism...
February 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#20
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
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