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https://www.readbyqxmd.com/read/29169184/her2-expression-patterns-in-paired-primary-and-metastatic-endometrial-cancer-lesions
#1
Mari Kyllesø Halle, Ingvild Løberg Tangen, Hege Fredriksen Berg, Erling Andre Hoivik, Karen K Mauland, Kanthida Kusonmano, Anna Berg, Antoni Hurtado, Karl Henning Kalland, Anne M Øyan, Ingunn Stefansson, Olav K Vintermyr, Henrica M Werner, Ingfrid S Haldorsen, Jone Trovik, Helga B Salvesen, Camilla Krakstad
BACKGROUND: Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers, the potential of HER2 as a therapeutic target in other cancers has been less studied, including endometrial cancer. We investigated expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions, also including complex atypical hyperplasia and metastatic lesions. METHODS: 67 precursor lesions, 790 primary endometrial cancers and 383 metastatic lesions were investigated for HER2 expression in relation to clinicopathologic features and outcome...
November 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29169183/myc-regulation-of-glutamine-proline-regulatory-axis-is-key-in-luminal-b-breast-cancer
#2
Madeleine L Craze, Hayley Cheung, Natasha Jewa, Nuno D M Coimbra, Daniele Soria, Rokaya El-Ansari, Mohammed A Aleskandarany, Kiu Wai Cheng, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Emad A Rakha, Andrew R Green
BACKGROUND: Altered cellular metabolism is a hallmark of cancer and some are reliant on glutamine for sustained proliferation and survival. We hypothesise that the glutamine-proline regulatory axis has a key role in breast cancer (BC) in the highly proliferative classes. METHODS: Glutaminase (GLS), pyrroline-5-carboxylate synthetase (ALDH18A1), and pyrroline-5-carboxylate reductase 1 (PYCR1) were assessed at DNA/mRNA/protein levels in large, well-characterised cohorts...
November 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29169174/melatonin-induced-changes-in-cytosolic-calcium-might-be-responsible-for-apoptosis-induction-in-tumour-cells
#3
Barbora Chovancova, Sona Hudecova, Lubomira Lencesova, Petr Babula, Ingeborg Rezuchova, Adela Penesova, Marian Grman, Roman Moravcik, Michal Zeman, Olga Krizanova
BACKGROUND/AIMS: Melatonin is a hormone transferring information about duration of darkness to the organism and is known to modulate several signaling pathways in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status of the cells, etc. Melatonin has been shown to exert antiproliferative and cytotoxic effects on various human cancers. We proposed that this hormone can differently affect tumour cells and healthy cells. METHODS: We compared the effect of 24 h melatonin treatment on calcium transport (by fluorescent probes FLUO-3AM and Rhod-5N), ER stress (determined as changes in the expression of CHOP, XBP1 and fluorescently, using Thioflavin T), ROS formation (by CellROX® Green/Orange Reagent) and apoptosis induction (by Annexin-V-FLUOS/propidiumiodide) in two tumour cell lines - ovarian cancer cell line A2780 and stable cell line DLD1 derived from colorectal carcinoma, with non-tumour endothelial cell line EA...
November 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29169168/anterior-borderzone-angle-for-hemodynamic-collateral-metric-in-patients-with-symptomatic-middle-cerebral-artery-stenosis
#4
Yongkun Li, Yunyun Xiong, Qiankun Cai, Dezhi Liu, Qiliang Dai, Wenhua Liu, Zhixin Huang, Wen Sun, David S Liebeskind, Yinzhou Wang, Xinfeng Liu
BACKGROUND AND AIMS: We aimed to introduce a parameter of anterior borderzone angle (ABZA) to quantitatively evaluate the ACA-MCA leptomeningeal collaterals for middle cerebral artery stenosis (MCAS). METHODS: Two hundred seventy-five patients with 50-100% MCAS and 100 controls were included. The 95% reference range of ABZA was obtained from the controls. ABZAtrans was defined as "ABZA/the 95% upper limit." Relationships between ABZA and MCAS, -ABZAtrans and the TICI grade, the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grade were analyzed...
November 23, 2017: European Neurology
https://www.readbyqxmd.com/read/29169155/rho-kinase-regulates-aortic-vascular-smooth-muscle-cell-stiffness-via-actin-srf-myocardin-in-hypertension
#5
Ning Zhou, Jia-Jye Lee, Shaunrick Stoll, Ben Ma, Kevin D Costa, Hongyu Qiu
BACKGROUND/AIMS: Our previous studies demonstrated that intrinsic aortic smooth muscle cell (VSMC) stiffening plays a pivotal role in aortic stiffening in aging and hypertension. However, the underlying molecular mechanisms remain largely unknown. We here hypothesized that Rho kinase (ROCK) acts as a novel mediator that regulates intrinsic VSMC mechanical properties through the serum response factor (SRF) /myocardin pathway and consequently regulates aortic stiffness and blood pressure in hypertension...
November 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29169153/optimal-trough-concentration-of-teicoplanin-in-febrile-neutropenic-patients-with-hematological-malignancy
#6
Yuhki Sato, Kazufumi Hiramatsu, Yosuke Suzuki, Ryota Tanaka, Tetsuya Kaneko, Ko Nonoshita, Masao Ogata, Jun-Ichi Kadota, Hiroki Itoh
BACKGROUND: Teicoplanin is a glycopeptide antibiotic currently used for the treatment of methicillin-resistant Staphylococcus aureus. The need for therapeutic drug monitoring of teicoplanin has been increasingly highlighted as important. It is generally accepted that whereas a plasma trough concentration (Cmin) of ≥10 mg/L is appropriate for the majority of infections, it should exceed 20 mg/L for severe infections. The target Cmin of teicoplanin in patients with febrile neutropenia (FN) has not been reported...
November 24, 2017: Chemotherapy
https://www.readbyqxmd.com/read/29169144/targeting-the-wnt-beta-catenin-pathway-in-cancer-update-on-effectors-and-inhibitors
#7
REVIEW
Nithya Krishnamurthy, Razelle Kurzrock
The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions like stem cell regeneration and organogenesis. Several intra-cellular signal transduction pathways are induced by Wnt, notably the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical or beta-catenin-independent pathway, the latter includes the Wnt/Ca2+ and Planar Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor, and is critical to optimal maintenance of stem cells...
November 13, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29169113/a-rapid-and-simple-hplc-ms-ms-method-for-the-simultaneous-quantification-of-valproic-acid-and-its-five-metabolites-in-human-plasma-and-application-to-study-pharmacokinetic-interaction-in-chinese-epilepsy-patients
#8
Dingsheng Wen, Ziyi Chen, Chao Yang, Huanbin Liu, Hongliang Li, Juan Chen, Qiling Dai, Guoping Zhong, Jiaming Qin, Guanzhong Ni, Min Huang, Liemin Zhou, Xueding Wang
Valproic acid(VPA) is a classic drug that used to treat epilepsy in monotherapy or combination with other anticonvulsant drugs such as lamotrigine (LTG). Although it was reported that VPA could increase lamotrigine trough concentration in clinical practice, there was no report about the effect of LTG on the trough concentration of VPA and its main metabolites, such as 4-ene-VPA, 3-OH-VPA, 4-OH-VPA, 3-keto-VPA, 2-PGA which are related to the therapeutic and toxic effects of VPA. In this study, a simple and rapid method for the simultaneous determination of VPA and its five metabolites in human plasma using HPLC-MS/MS was developed for the first time...
November 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29169088/systematically-investigating-the-impact-of-medication-on-the-gut-microbiome
#9
REVIEW
Lisa Maier, Athanasios Typas
In the recent years, there is accumulating evidence for a strong impact of medication on the gut microbiota composition. This evidence comes from metagenomics-based associations and extends beyond classical antibacterials to a handful of human-targeted drugs. To answer whether such effects are direct and explore their consequences in human health, we need to develop experimental platforms that will allow for systematic profiling of drug-microbiota interactions. Here, we discuss approaches, considerations, experimental setups and strategies that can be used to tackle this need, but can be also readily transmitted to related questions in the microbiome field...
November 20, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29169078/amino-acids-peptides-conjugated-heterocycles-a-tool-for-the-recent-development-of-novel-therapeutic-agents
#10
REVIEW
Meng Wang, K P Rakesh, Jing Leng, Wan-Yin Fang, L Ravindar, D Channe Gowda, Hua-Li Qin
Amino acids/peptide conjugated heterocycles represent an important class of therapeutical agents. Biologically active heterocycles are conjugated with amino acids or peptides to increase the drug resistance. Furthermore, the amino acid/peptide based drugs have low toxicity, ample bioavailability and permeability, modest potency and good metabolic and pharmacokinetic properties. Synthetic amino acid/peptides based heterocyclic conjugates constitute a promising choice for the development of new, less toxic and safer conventional pharmaceutical drugs in the near future...
November 16, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29169047/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy-linked-to-mutations-in-asah1
#11
Edibe Pembegül Yildiz, Gözde Yesil, Gonca Bektas, Mine Caliskan, Burak Tatlı, Nur Aydinli, Meral Ozmen
Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), a rare disorder caused by mutation in the ASAH1 gene, is characterized by progressive muscle weakness and intractable epilepsy. The literature about SMA-PME is very rare and most of the time limited to case reports. Mutation in the ASAH1 gene is also found in another rare syndrome which is Farber disease. We report a case of a 13.5-year-old girl with SMA-PME associated with ASAH1 gene mutation. She presented with progressive muscle weakness, tremor, seizure, and cognitive impairment...
November 20, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29169044/esculentoside-a-specifically-binds-to-ribosomal-protein-s3a-and-impairs-lps-induced-signaling-in-macrophages
#12
Ying-Hua Li, Jing Wang, Ying Liu, Lie Qiu, Jian-Zhong Li, Hong-Gang Hu, Zhen-Lin Hu, Wen Zhang, Bin Lu, Jun-Ping Zhang
Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, is reported as a potent suppressor of pro-inflammatory functions of macrophages. However, little is known about the target proteins of EsA for its anti-inflammatory activity. In the present study, to identify the intracellular target for EsA, affinity resins bearing immobilized EsA were used to capture binding proteins of EsA from RAW264.7 cell lysates. Mass spectrography and Western blot analysis of captured proteins indicated that ribosomal protein S3a preferentially bound to EsA affinity resin...
November 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29169038/theranostic-2d-ultrathin-mno2-nanosheets-with-fast-responsibility-to-endogenous-tumor-microenvironment-and-exogenous-nir-irradiation
#13
Zhuang Liu, Shengjian Zhang, Han Lin, Menglong Zhao, Heliang Yao, Linlin Zhang, Weijun Peng, Yu Chen
The fabrication of functional nanoparticles with unique ultra-sensitivity to endogenous tumor microenvironment (TME) is of great significance for their improved theranostic performance and easy excretion out of the body, which has not been realized among diverse nano-sized photothermal agents for photothermal therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin MnO2 nanosheets for highly efficient PTT against tumor with ultra-sensitivity to endogenous TME. These ultrathin 2D MnO2 nanosheets show the intriguing characteristic of disintegration and releasing of Mn(2+) in response to the mild acidic condition and elevated reducing microenvironment of TME, which has successfully realized the pH- and reducing-responsive T1-weighted magnetic resonance imaging of tumor...
November 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/29169028/relationships-of-depression-and-anxiety-symptoms-with-seizure-frequency-results-from-a-multicenter-follow-up-study
#14
Lorenz B Dehn, Margarete Pfäfflin, Sabine Brückner, Martin T Lutz, Bernhard J Steinhoff, Thomas Mayer, Christian G Bien, Fridtjof W Nussbeck, Theodor W May
PURPOSE: Depressive and anxiety disorders are frequent among people with epilepsies. There are, however, only few longitudinal studies, which examine the relationship between these comorbid psychiatric disorders and epilepsy-related variables. Thus, we investigated the interrelationships of depression and anxiety symptoms with seizure frequency across time. METHODS: Before admittance to an epilepsy center (T1) and six months after discharge (T2), patients (n=198) with mainly difficult-to-treat epilepsies completed the Hospital Anxiety and Depression Scale (HADS)...
November 13, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29168980/inability-to-reduce-morbidity-of-diarrhea-by-ors-can-we-design-a-better-therapy
#15
Jane E Harrell, Sam X Cheng
Diarrheal disease is a worldwide problem that still causes significant morbidity and mortality among children. Currently, oral rehydration solution (ORS) is the standard of care for acute diarrhea in pediatric patients. While effective in reducing mortality, ORS does not alleviate diarrheal symptoms, thus reducing caregiver compliance and therapeutic efficacy. This manuscript will briefly review the current problem of pediatric diarrhea and the shortcomings of current therapies; however, the focus of this review is to examine the intestinal calcium-sensing receptor (CaSR)...
November 23, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29168929/kinin-b1-receptors-as-a-therapeutic-target-for-inflammation
#16
Fatimunnisa Qadri, Michael Bader
Kinins are peptide mediators exerting their pro-inflammatory actions by the selective stimulation of two distinct G-protein coupled receptors, termed BKB1R and BKB2R. While BKB2R is constitutively expressed in a multitude of tissues, BKB1R is hardly expressed at baseline but highly inducible by inflammatory mediators. In particular, BKB1R was shown to be involved in the pathogenesis of numerous inflammatory diseases. Areas covered: This review intends to evaluate the therapeutic potential of substances interacting with the BKB1R...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168923/calpain-2-as-a-therapeutic-target-for-acute-neuronal-injury
#17
Yubin Wang, Xiaoning Bi, Michel Baudry
Introduction Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where calpain-1 and calpain-2 are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpain-2 in acute neuronal injury and discuss the possibility of developing selective calpain-2 inhibitors for therapeutic purposes...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168879/1p36-deletion-results-in-a-decrease-in-glycosaminoglycans-which-is-associated-with-aggressiveness-in-neuroblastic-tumors
#18
Irene Tadeo, Esther Gamero-Sandemetrio, Ana P Berbegall, Samuel Navarro, Adela Cañete, Rosa Noguera
Despite our deep understanding of neuroblastic tumors, some patients still suffer treatment failure, so pre-treatment risk stratification still requires improvement and the search for new therapeutic targets must continue. Here we correlated prognostic clinical and biological features of neuroblastic tumors with the density of extracellular matrix glycosaminoglycans (the main components of the extracellular matrix 'ground substance'), in nearly 400 primary samples. We also studied the relationship between the density of extracellular matrix glycosaminoglycans and the expression of B3GALT6, an enzyme required for their synthesis...
November 23, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/29168872/organoselenium-compounds-as-mimics-of-selenoproteins-and-thiol-modifier-agents
#19
REVIEW
Nilda V Barbosa, Cristina W Nogueira, Pablo A Nogara, Andreza F de Bem, Michael Aschner, João B T Rocha
Selenium is an essential trace element for animals and its role in the chemistry of life relies on a unique functional group: the selenol (-SeH) group. The selenol group participates in critical redox reactions. The antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) exemplify important selenoproteins. The selenol group shares several chemical properties with the thiol group (-SH), but it is much more reactive than the sulfur analogue. The substitution of S by Se has been exploited in organic synthesis for a long time, but in the last 4 decades the re-discovery of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) and the demonstration that it has antioxidant and therapeutic properties has renovated interest in the field...
November 23, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29168791/administration-of-protocatechuic-acid-reduces-traumatic-brain-injury-induced-neuronal-death
#20
Sang Hwon Lee, Bo Young Choi, Song Hee Lee, A Ra Kho, Jeong Hyun Jeong, Dae Ki Hong, Sang Won Suh
Protocatechuic acid (PCA) was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)-induced neuronal death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes neuronal death in the hippocampus and cerebral cortex...
November 23, 2017: International Journal of Molecular Sciences
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