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https://www.readbyqxmd.com/read/28638453/the-clinical-impact-of-c-met-over-expression-in-advanced-biliary-tract-cancer-btc
#1
Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Kyoung-Mee Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park, Seung Tae Kim
Background: c-MET is a proto-oncogene that encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF). Activation of HGF-c-MET signaling involves cell invasiveness and evokes metastasis through direct involvement of tumor angiogenesis. However, the value of c-MET overexpression is still unknown in metastatic biliary tract cancer (BTC). Methods: We analyzed the incidence and clinicopathologic characteristics of c-MET overexpression in advanced BTC. Moreover, we investigated the value of c-MET overexpression in predicting response to gemicitabine plus cisplatin (GC), a first line standard regimen, and as a prognostic marker in metastatic BTC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28634817/identification-of-the-acclimation-genes-in-transcriptomic-responses-to-heat-stress-of-white-pekin-duck
#2
Jun-Mo Kim, Kyu-Sang Lim, Mijeong Byun, Kyung-Tai Lee, Young-Rok Yang, Mina Park, Dajeong Lim, Han-Ha Chai, Han-Tae Bang, Jong Hwangbo, Yang-Ho Choi, Yong-Min Cho, Jong-Eun Park
White Pekin duck is an important meat resource in the livestock industries. However, the temperature increase due to global warming has become a serious environmental factor in duck production, because of hyperthermia. Therefore, identifying the gene regulations and understanding the molecular mechanism for adaptation to the warmer environment will provide insightful information on the acclimation system of ducks. This study examined transcriptomic responses to heat stress treatments (3 and 6 h at 35 °C) and control (C, 25 °C) using RNA-sequencing analysis of genes from the breast muscle tissue...
June 20, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28634071/the-novel-yap-target-gene-sgk1-upregulates-taz-activity-by-blocking-gsk3%C3%AE-mediated-taz-destabilization
#3
Geon Yoo, Tackhoon Kim, Chaeuk Chung, Deog-Su Hwang, Dae-Sik Lim
YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28625535/glial-specific-functions-of-microcephaly-protein-wdr62-and-interaction-with-the-mitotic-kinase-aurka-are-essential-for-drosophila-brain-growth
#4
Nicholas R Lim, Belal Shohayeb, Olga Zaytseva, Naomi Mitchell, S Sean Millard, Dominic C H Ng, Leonie M Quinn
The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume...
June 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28622474/larch-arabinogalactan-attenuates-myocardial-injury-by-inhibiting-apoptotic-cascades-in-a-rat-model-of-ischemia-reperfusion
#5
Sun-Ha Lim
We reported previously that supplementation with apple pectin, a dietary fiber, reduced myocardial injury in a rat model of ischemia-reperfusion. In this study, we further investigated an arabinogalactan, one of the constituent polysaccharides of pectin, to determine which domains comprising pectin were responsible for the protection. In a rat model of 30-min ischemia followed by 3-h reperfusion, supplementation with larch arabinogalactan (LAG) over 50 mg/kg/day significantly reduced infarct size. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot analyses showed that intake of LAG blocked the steps involved in apoptotic cascades through downregulation of gelsolin gene expression at the protein (Gelsolin) level, inhibition of p38 phosphorylation in mitogen-activated protein kinase (MAPK) pathways, decreased bax/bcl-2 ratio at the protein (Bax/Bcl-2) level, which was correlated with the ratio at the mRNA level, inhibition of the conversion of Procaspase protein to Caspase-3 protein, and consequently a decrease in apoptotic cells...
June 16, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28607076/functional-proteogenomics-reveals-biomarkers-and-therapeutic-targets-in-lymphomas
#6
Delphine C M Rolland, Venkatesha Basrur, Yoon-Kyung Jeon, Carla McNeil-Schwalm, Damian Fermin, Kevin P Conlon, Yeqiao Zhou, Samuel Y Ng, Chih-Chiang Tsou, Noah A Brown, Dafydd G Thomas, Nathanael G Bailey, Gilbert S Omenn, Alexey I Nesvizhskii, David E Root, David M Weinstock, Robert B Faryabi, Megan S Lim, Kojo S J Elenitoba-Johnson
Identification of biomarkers and therapeutic targets is a critical goal of precision medicine. N-glycoproteins are a particularly attractive class of proteins that constitute potential cancer biomarkers and therapeutic targets for small molecules, antibodies, and cellular therapies. Using mass spectrometry (MS), we generated a compendium of 1,091 N-glycoproteins (from 40 human primary lymphomas and cell lines). Hierarchical clustering revealed distinct subtype signatures that included several subtype-specific biomarkers...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28598765/shigella-depends-on-sepa-to-destabilize-the-intestinal-epithelial-integrity-via-cofilin-activation
#7
Ana Maldonado-Contreras, James R Birtley, Erik Boll, Yun Zhao, Karen L Mumy, Juan Toscano, Seyoum Ayehunie, Hans-Christian Reinecker, Lawrence J Stern, Beth A McCormick
Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions...
June 9, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28588454/reelin-signaling-inactivates-cofilin-to-stabilize-the-cytoskeleton-of-migrating-cortical-neurons
#8
REVIEW
Michael Frotscher, Shanting Zhao, Shaobo Wang, Xuejun Chai
Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28584195/cdk-dependent-phosphorylation-of-sox2-at-serine-39-regulates-neurogenesis
#9
Shuhui Lim, Akshay Bhinge, Sara Bragado Alonso, Irene Aksoy, Julieta Aprea, Chit Fang Cheok, Federico Calegari, Lawrence W Stanton, Philipp Kaldis
Sox2 is known to be important for neuron formation but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal remain elusive. Here, we identify a highly conserved Cdk phosphorylation site on serine 39 (S39) in Sox2. In neural stem cells (NSCs), phosphorylation of S39 enhances the ability of Sox2 to negatively regulate neuronal differentiation, while loss of phosphorylation is necessary for chromatin retention of a truncated form of Sox2 generated during neurogenesis...
June 5, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28581515/gata3-targets-semaphorin-3b-in-mammary-epithelial-cells-to-suppress-breast-cancer-progression-and-metastasis
#10
P Shahi, C-Y Wang, J Chou, C Hagerling, H Gonzalez Veloso, A Ruderisch, Y Yu, M-D Lai, Z Werb
Semaphorin 3B (SEMA3B) is a secreted axonal guidance molecule that is expressed during development and throughout adulthood. Recently, SEMA3B has emerged as a tumor suppressor in non-neuronal cells. Here, we show that SEMA3B is a direct target of GATA3 transcriptional activity. GATA3 is a key transcription factor that regulates genes involved in mammary luminal cell differentiation and tumor suppression. We show that GATA3 relies on SEMA3B for suppression of tumor growth. Loss of SEMA3B renders GATA3 inactive and promotes aggressive breast cancer development...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28580603/enhancement-of-high-glucose-induced-pink1-expression-by-melatonin-stimulates-neuronal-cell-survival-involvement-of-mt2-akt-nf-%C3%AE%C2%BAb-pathway
#11
Xaykham Onphachanh, Hyun Jik Lee, Jae Ryong Lim, Young Hyun Jung, Jun Sung Kim, Chang Woo Chae, Sei-Jung Lee, Amr Ahmed Gabr, Ho Jae Han
Hyperglycemia is a representative hallmark and risk factor for diabetes mellitus (DM) and is closely linked to DM-associated neuronal cell death. Previous investigators reported on a genome-wide association study and showed relationships between DM and melatonin receptor (MT), highlighting the role of MT signaling by assessing melatonin in DM. However, the role of MT signaling in DM pathogenesis is unclear. Therefore, we investigated the role of mitophagy regulators in high glucose-induced neuronal cell death and the effect of melatonin against high glucose-induced mitophagy regulators in neuronal cells...
June 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28579481/scientific-advances-in-thoracic-oncology-2016
#12
REVIEW
Ross A Soo, Emily Ca Stone, K Michael Cummings, James R Jett, John K Field, Harry Jm Groen, James L Mulshine, Yasushi Yatabe, Lukas Bubendorf, Sanja Dacic, Ramon Rami-Porta, Frank C Detterbeck, Eric Lim, Hisao Asamura, Jessica Donington, Heather A Wakelee, Yi Long Wu, Kristin Higgins, Suresh Senan, Benjamin Solomon, Dong-Wan Kim, Melissa Johnson, James Ch Yang, Lecia V Sequist, Alice T Shaw, Myung-Ju Ahn, Daniel B Costa, Jyoti D Patel, Leora Horn, Scott Gettinger, Solange Peters, Murry W Wynes, Corinne Faivre-Finn, Charles M Rudin, Anne Tsao, Paul Baas, Ronan J Kelly, Natasha B Leighl, Giorgio V Scagliotti, David R Gandara, Fred R Hirsch, David R Spigel
Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The IASLC and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for non-small cell lung cancer, small cell lung cancer, and mesothelioma...
May 27, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28576487/mek-and-pi3k-catalytic-activity-as-predictor-of-the-response-to-molecularly-targeted-agents-in-triple-negative-breast-cancer
#13
Natsuki Sato, Masayuki Wakabayashi, Masatoshi Nakatsuji, Haruka Kashiwagura, Naohiro Shimoji, Shiho Sakamoto, Atsuko Ishida, Jangsoon Lee, Bora Lim, Naoto T Ueno, Hideki Ishihara, Takashi Inui
Hyper-activation of the MAPK and PI3K-AKT pathways is linked to tumour progression in triple-negative breast cancer (TNBC). However, clinically effective predictive markers for drugs targeted against protein kinases involved in these pathways have not been identified. We investigated the ability of MEK and PI3K catalytic activity to predict sensitivity to trametinib and wortmannin in TNBC. MEK and PI3K activities correlated strongly with each other only in cell lines showing wortmannin-specific sensitivity, as shown by a linear regression curve (R = 0...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28574509/mycn-amplified-neuroblastoma-requires-the-mrna-translation-regulator-eef2-kinase-to-adapt-to-nutrient-deprivation
#14
Alberto Delaidelli, Gian Luca Negri, Asad Jan, Brandon Jansonius, Amal El-Naggar, Jonathan K M Lim, Debjit Khan, Htoo Zarni Oo, Christopher J Carnie, Marc Remke, John M Maris, Gabriel Leprivier, Poul H Sorensen
MYC family proteins are implicated in many human cancers, but their therapeutic targeting has proven challenging. MYCN amplification in childhood neuroblastoma (NB) is associated with aggressive disease and high mortality. Novel and effective therapeutic strategies are therefore urgently needed for these tumors. MYC-driven oncogenic transformation impairs cell survival under nutrient deprivation (ND), a characteristic stress condition within the tumor microenvironment. We recently identified eukaryotic Elongation Factor 2 Kinase (eEF2K) as a pivotal mediator of the adaptive response of tumor cells to ND...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28573459/cytoskeleton-associated-risk-modifiers-involved-in-early-and-rapid-progression-of-sporadic-creutzfeldt-jakob-disease
#15
Saima Zafar, Neelam Younas, Nadeem Sheikh, Waqas Tahir, Mohsin Shafiq, Matthias Schmitz, Isidre Ferrer, Olivier Andréoletti, Inga Zerr
A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. In this study, we demonstrate the pre-symptomatic dysregulation of cytoskeleton assembly and its associated cofilin-1 pathway in strain and brain region-specific manners in MM1 and VV2 subtype-specific Creutzfeldt-Jakob disease at clinical and pre-clinical stage. At physiological level, PrP(C) interaction with cofilin-1 and phosphorylated form of cofilin (p-cofilin(Ser3)) was investigated in primary cultures of mouse cortex neurons (PCNs) of PrP(C) wild-type and knockout mice (PrP(-/-))...
June 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28566623/moutan-cortex-protects-hepatocytes-against-oxidative-injury-through-amp-activated-protein-kinase-pathway
#16
Mi Hee Jang, Kwang-Youn Kim, Phil Hyun Song, Su Youn Baek, Hye Lim Seo, Eun Hye Lee, Suel-Gi Lee, Kwang Il Park, Soon-Cheol Ahn, Sang Chan Kim, Young Woo Kim
Moutan Cortex, the root bark of Paeonia suffruticosa ANDREWS in Ranunculaceae, has widely demonstrated analgesic, anti-spasmodic, and anti-inflammatory effects in various cancer and immune cell lines. Oxidative stress is associated with development of several diseases, including liver disease. We prepared the water extract of Moutan Cortex (MCE) to investigate the cytoprotective activities and its mechanism. MCE protected hepatocytes from arachidonic acid (AA)+iron induced oxidative stress, as indicated by reactive oxygen species (ROS) production and cell viability analysis...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28562588/a-cryptosporidium-pi-4-k-inhibitor-is-a-drug-candidate-for-cryptosporidiosis
#17
Ujjini H Manjunatha, Sumiti Vinayak, Jennifer A Zambriski, Alexander T Chao, Tracy Sy, Christian G Noble, Ghislain M C Bonamy, Ravinder R Kondreddi, Bin Zou, Peter Gedeck, Carrie F Brooks, Gillian T Herbert, Adam Sateriale, Jayesh Tandel, Susan Noh, Suresh B Lakshminarayana, Siau H Lim, Laura B Goodman, Christophe Bodenreider, Gu Feng, Lijun Zhang, Francesca Blasco, Juergen Wagner, F Joel Leong, Boris Striepen, Thierry T Diagana
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28562031/europium-labeled-synthetic-c3a-protein-as-a-novel-fluorescent-probe-for-human-complement-c3a-receptor
#18
Aline Dantas de Araujo, Chongyang Wu, Kai-Chen Wu, Robert C Reid, Thomas Durek, Junxian Lim, David P Fairlie
Measuring ligand affinity for a G protein-coupled receptor is often a crucial step in drug discovery. It has been traditionally determined by binding putative new ligands in competition with native ligand labeled with a radioisotope of finite lifetime. Competing instead with a lanthanide-based fluorescent ligand is more attractive due to greater longevity, stability, and safety. Here, we have chemically synthesized the 77 residue human C3a protein and conjugated its N-terminus to europium diethylenetriaminepentaacetate to produce a novel fluorescent protein (Eu-DTPA-hC3a)...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28559978/mir-143-3p-targeting-lim-domain-kinase-1-suppresses-the-progression-of-triple-negative-breast-cancer-cells
#19
Dengfeng Li, Jiashu Hu, Hongming Song, Hui Xu, Chengyang Wu, Bingkun Zhao, Dan Xie, Tianqi Wu, Junyong Zhao, Lin Fang
Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer is one of the most aggressive types of breast cancer as it has the worst clinical outcome for patients. microRNAs are a type of small non-coding RNA and play an important role in breast cancer. The purpose of this study was to explore the potential function and mechanism of miR-143-3p in triple-negative breast cancer (TNBC). MTT and colony formation assays, the effect of miR-143-3p modulation on MDA-MB-231 cell proliferation, revealed that increased miR-143-3p expression inhibited the proliferation of MDA-MB-231 TNBC cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28554197/a-new-neolignan-derivative-balanophonin-isolated-from-firmiana-simplex-delays-the-progress-of-neuronal-cell-death-by-inhibiting-microglial-activation
#20
Soo Young Lim, Lalita Subedi, Dongyun Shin, Chung Sub Kim, Kang Ro Lee, Sun Yeou Kim
Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of Balanophonin in Lipopolysaccharide (LPS)-stimulated BV2 microglia cells...
May 30, 2017: Biomolecules & Therapeutics
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