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https://www.readbyqxmd.com/read/29771169/associations-between-skin-rash-treatment-outcome-and-single-nucleotide-polymorphisms-in-head-and-neck-cancer-patients-receiving-the-egfr-inhibitor-zalutumumab-results-from-the-dahanca-19-trial
#1
Line Brøndum, Jan Alsner, Brita Singers Sørensen, Christian Maare, Jørgen Johansen, Hanne Primdahl, Jan Folkvard Evensen, Claus Andrup Kristensen, Lisbeth Juhler Andersen, Jens Overgaard, Jesper Grau Eriksen
PURPOSE: To study the associations between development of moderate to severe skin rash, clinical outcome, and single nucleotide polymorphisms (SNPs) in candidate genes in head and neck cancer patients from the DAHANCA 19 trial receiving the EGFR-inhibitor zalutumumab concurrently with radiation treatment. MATERIAL AND METHODS: 310 patients were included from the zalutumumab-arm of the DAHANCA 19 study. Nine SNPs in the candidate genes EGFR, EGF, AREG, FCGR2A, FCGR3A, and CCND1 were successfully determined in 294 patients...
May 17, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29716588/prostaglandin-e2-involvement-in-mammalian-female-fertility-ovulation-fertilization-embryo-development-and-early-implantation
#2
REVIEW
Jean Damascene Niringiyumukiza, Hongcai Cai, Wenpei Xiang
BACKGROUND: Infertility in mammalian females has been a challenge in reproductive medicine. The causes of female infertility include anovulation, ovulated oocyte defects, abnormal fertilization, and insufficient luteal support for embryo development, as well as early implantation. Ovulation induction, in vitro fertilization and luteal support regimens have been performed for decades to increase fertility rates. The identification of proteins and biochemical factors involved in female reproduction is essential to further increase female fertility rates...
May 1, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29682330/yes-associated-protein-yap-in-pancreatic-cancer-at-the-epicenter-of-a-targetable-signaling-network-associated-with-patient-survival
#3
Enrique Rozengurt, James Sinnett-Smith, Guido Eibl
Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29663383/nanoparticle-based-targeted-cancer-strategies-for-non-invasive-prostate-cancer-intervention
#4
REVIEW
Nicholas H Farina, Areg Zingiryan, Michael A Vrolijk, Scott D Perrapato, Steven Ades, Gary S Stein, Jane B Lian, Christopher C Landry
Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over-diagnosis and over-treatment...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662625/adam17-inhibition-enhances-platinum-efficiency-in-ovarian-cancer
#5
Nina Hedemann, Christoph Rogmans, Susanne Sebens, Daniela Wesch, Manuel Reichert, Dirk Schmidt-Arras, Hans-Heinrich Oberg, Ulrich Pecks, Marion van Mackelenbergh, Jörg Weimer, Norbert Arnold, Nicolai Maass, Dirk O Bauerschlag
Chemotherapeutic resistance evolves in about 70 % of ovarian cancer patients and is a major cause of death in this tumor entity. Novel approaches to overcome these therapeutic limitations are therefore highly warranted. A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in ovarian cancer and required for releasing epidermal growth factor receptor (EGFR) ligands like amphiregulin (AREG). This factor has recently been detected in ascites of advanced stage ovarian cancer patients. However, it is not well understood, whether and how ADAM17 might contribute to chemo resistance of ovarian cancer...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29660395/endogenous-pgi-2-signaling-through-ip-inhibits-neutrophilic-lung-inflammation-in-lps-induced-acute-lung-injury-mice-model
#6
Shinji Toki, Weisong Zhou, Kasia Goleniewska, Sara Reiss, Daniel E Dulek, Dawn C Newcomb, William E Lawson, R Stokes Peebles
Endogenous prostaglandin I2 (PGI2 ) has inhibitory effects on immune responses against pathogens or allergens; however, the immunomodulatory activity of endogenous PGI2 signaling in endotoxin-induced inflammation is unknown. To test the hypothesis that endogenous PGI2 down-regulates endotoxin-induced lung inflammation, C57BL/6 wild type (WT) and PGI2 receptor (IP) KO mice were challenged intranasally with LPS. Urine 6-keto-PGF1α , a stable metabolite of PGI2, was significantly increased following the LPS-challenge, suggesting that endogenous PGI2 signaling modulates the host response to LPS-challenge...
April 13, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29645082/soluble-st2-sst2-regulation-by-rhinovirus-rv-and-25-oh-vitamin-d3-in-the-blood-of-asthmatic-children
#7
Patricia Haag, Himanshu Sharma, Manfred Rauh, Theodor Zimmermann, Tytti Vuorinen, Nikolaos G Papadopoulos, Scott T Weiss, Susetta Finotto
Paediatric asthma exacerbations are often caused by Rhinovirus (RV). Moreover, 25(OH)-Vitamin D3 (=25(OH) VitD3) deficiency during infancy was found associated with asthma. Here, we investigated the innate immune responses to RV and their possible modulation by 25(OH) VitD3 serum levels in a preschool cohort of children with and without asthma. The innate lymphoid cell type 2 (ILC2)-associated marker, ST2 was found upregulated in the blood cells of asthmatic children with low serum levels of 25(OH)VitD3 in the absence of RV in their airways...
April 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29593273/nuclear-disarmament-verification-via-resonant-phenomena
#8
Jake J Hecla, Areg Danagoulian
Nuclear disarmament treaties are not sufficient in and of themselves to neutralize the existential threat of the nuclear weapons. Technologies are necessary for verifying the authenticity of the nuclear warheads undergoing dismantlement before counting them toward a treaty partner's obligation. Here we present a concept that leverages isotope-specific nuclear resonance phenomena to authenticate a warhead's fissile components by comparing them to a previously authenticated template. All information is encrypted in the physical domain in a manner that amounts to a physical zero-knowledge proof system...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29550478/cullin-3-regulates-adams-mediated-ectodomain-shedding-of-amphiregulin
#9
Hironao Nakayama, Tomohisa Sakaue, Masashi Maekawa, Ayako Fujisaki, Shigeki Higashiyama
A disintegrin and metalloproteinase (ADAM) family are crucial enzymes for ectodomain shedding of multiple substrates and are involved in diverse biologic and pathologic processes. However, the molecular mechanism underlying substrate selectivity of ADAMs is poorly understood. In this study, we observed that disruption of actin polymerization by pharmacological inhibitors, latrunculin A (LatA) and cytochalasin D (CyD), induced ectodomain shedding of epidermal growth factor (EGF) family ligands. Induced shedding activity by LatA or CyD was suppressed by a metalloprotease inhibitor KB-R7785, indicating that ADAMs-mediated shedding is tightly controlled by actin cytoskeleton...
April 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29540993/the-egfr-adam17-axis-in-chronic-obstructive-pulmonary-disease-and-cystic-fibrosis-lung-pathology
#10
REVIEW
Marta Stolarczyk, Bob J Scholte
Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R)...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29516335/stromal-derived-factor-1-directly-promotes-genes-expressed-within-the-ovulatory-cascade-in-feline-cumulus-oocyte-complexes
#11
Julieta L Rojo, Martina Linari, Kelly A Young, Marina C Peluffo
PURPOSE: We hypothesized that the chemokine SDF1/CXCR4 system was present in feline cumulus-oocyte complexes (COCs) and that COCs cultured with SDF1 would directly upregulate gene expression in the ovulatory cascade. METHODS: Ovaries (n = 50) were obtained from adult domestic cats during the breeding season and COCs were recovered from antral follicles. Because IVM media triggers cumulus-oocyte expansion, culture conditions needed to be optimized to study periovulatory genes...
March 8, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29511771/risk-of-hysterectomy-and-salpingectomy-or-oophorectomy-compared-to-repair-after-pelvic-gynecologic-trauma
#12
Areg Grigorian, Victor Joe, Patrick Thomas Delaplain, Sebastian Schubl, Bel Barker, Viktor Gabriel, Austin Ronald Dosch, Cristobal Barrios, Jeffry Nahmias
PURPOSE: Pelvic gynecologic trauma (PGT) includes injury to the uterus, ovaries or fallopian tubes. We hypothesized Injury Severity Score (ISS) ≥ 25, hypotension on admission and age ≥ 51 (average age for menopause) would be independent risk factors for resection compared to repair. METHODS: A retrospective analysis of the National Trauma Data Bank was performed between 2007 and 2015. RESULTS: Of 2,040,235 female patients, 1938 (< 0...
March 6, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29506988/phase-ii-study-of-the-dual-egfr-her3-inhibitor-duligotuzumab-mehd7945a-versus-cetuximab-in-combination-with-folfiri-in-second-line-ras-wild-type-metastatic-colorectal-cancer
#13
Andrew G Hill, Michael P Findlay, Matthew E Burge, Christopher Jackson, Pilar Garcia Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffery, Maria Di Bartolomeo, John Bridgewater, Andrew L Coveler, Manuel Hidalgo, Amy V Kapp, Roxana I Sufan, Bruce B McCall, William D Hanley, Elicia M Penuel, Andrea Pirzkall, Josep Tabernero
Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental Design: Metastatic colorectal cancer (mCRC) patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomly assigned patients, 98 had RAS ex2/3 wild-type. Duligotuzumab provided no progression-free survival (PFS) or overall survival (OS) benefit compared with cetuximab, although there was a trend for a lower objective response rate (ORR) in the duligotuzumab arm...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29503399/effect-of-pre-in-vitro-maturation-with-camp-modulators-on-the-acquisition-of-oocyte-developmental-competence-in-cattle
#14
Satoshi Sugimura, Tadayuki Yamanouchi, Maria Grazia Palmerini, Yutaka Hashiyada, Kei Imai, Robert B Gilchrist
The administration of follicle-stimulating hormone (FSH) prior to oocyte retrieval improves oocyte developmental competence. During bovine embryo production in vitro, however, oocytes are typically derived from FSH-unprimed animals. In the current study, we examined the effect of pre-in vitro maturation (IVM) with cAMP modulators, also known as the second messengers of FSH, on the developmental competence of oocytes derived from small antral follicles (2-4 mm) of FSH-unprimed animals. Pre-IVM with N6,2'-O-dibutyryladenosine 3',5'-cyclicmonophosphate (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX) for 2 h improved the blastocyst formation in oocytes stimulated by FSH or amphiregulin (AREG)...
March 2, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29483579/hypoxia-inducible-factor-2-alpha-dependent-induction-of-amphiregulin-dampens-myocardial-ischemia-reperfusion-injury
#15
Michael Koeppen, Jae W Lee, Seong-Wook Seo, Kelley S Brodsky, Simone Kreth, Ivana V Yang, Peter M Buttrick, Tobias Eckle, Holger K Eltzschig
Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes...
February 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29420611/inductions-of-granulosa-cell-luteinization-and-cumulus-expansion-are-dependent-on-the-fibronectin-integrin-pathway-during-ovulation-process-in-mice
#16
Hiroya Kitasaka, Tomoko Kawai, S A Masudul Hoque, Takashi Umehara, Youko Fujita, Masayuki Shimada
It has been known that EGF-like factor secreted from LH-stimulated granuloma cells acts on granulosa cells and cumulus cells to induce ovulation process. Granulosa cells are changed the morphology with differentiating cell functions to produce progesterone. Cumulus cells are detached to make a space between the cells to accumulate hyaluronan rich matrix. LH also changes extracellular matrix (ECM) components including fibronectin in the follicular walls and granulosa cell layers. EGF like factor and fibronectin synergistically play important roles in numerous cell functions, especially cancer cell migration, estimating that fibronectin would impact on granulosa cells and cumulus cells...
2018: PloS One
https://www.readbyqxmd.com/read/29375042/effect-of-bone-morphogenetic-protein-15-on-gonadotropin-stimulated-synthesis-of-hyaluronan-and-progesterone-in-porcine-ovarian-follicle
#17
E Nagyova, L Nemcova, A Bujnakova Mlynarcikova, M Blaha, R Prochazka, S Scsukova
Bone morphogenetic protein-15 (BMP-15), an oocyte-derived growth factor, has been shown to play integral roles in regulation of ovarian follicular function in mammals. Despite the recognition of the physiological importance of the BMP system in regulation of gonadotropin action in the ovary, molecular mechanisms of BMP-15 effect on oocyte and somatic follicular cell functions remain poorly understood. The objective of this study was to determine the effect of BMP-15 on the FSH/LH-stimulated synthesis of hyaluronan (HA) by oocyte cumulus complexes (OCC) and progesterone by OCC and granulosa cells (GC) in the presence or absence of serum using primary porcine cultures...
October 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29351448/extracellular-oxidation-in-cystic-fibrosis-airway-epithelium-causes-enhanced-egfr-adam17-activity
#18
Marta Stolarczyk, Guido Veit, Andrea Schnúr, Mieke Veltman, Gergely L Lukacs, Bob J Scholte
The EGF receptor (EGFR)/a disintegrin and metalloproteinase 17 (ADAM17) signaling pathway mediates the shedding of growth factors and secretion of cytokines and is involved in chronic inflammation and tissue remodeling. Since these are hallmarks of cystic fibrosis (CF) lung disease, we hypothesized that CF transmembrane conductance regulator (CFTR) deficiency enhances EGFR/ADAM17 activity in human bronchial epithelial cells. In CF bronchial epithelial CFBE41o- cells lacking functional CFTR (iCFTR- ) cultured at air-liquid interface (ALI) we found enhanced ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared with genetically identical cells with induced CFTR expression (iCFTR+ )...
April 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29341420/transgenic-mice-specifically-expressing-amphiregulin-in-white-adipose-tissue-showed-less-adipose-tissue-mass
#19
Bo Yang, Takahiro Kumoto, Takeshi Arima, Minako Nakamura, Yohei Sanada, Thanutchaporn Kumrungsee, Yusuke Sotomaru, Masayuki Shimada, Noriyuki Yanaka
To determine adipocytokines that play a regulatory role during obesity development, we explored the genes that encode growth factors and investigated the physiological functions for adipose tissue development. Here, we isolated amphiregulin (Areg) gene whose expression was significantly up-regulated in obese adipose tissues. Areg mRNA level was positively correlated with macrophage marker gene expression in adipose tissues in vivo. Unexpectedly, Areg transgenic mice showed less adipose tissue mass with increased mRNA expression levels of Tnf-α and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α) and delayed white adipose tissue development during the convalescent stage in a dextran sodium sulfate-induced colitis model...
January 17, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29316908/efficacy-and-safety-of-curcumin-and-its-combination-with-boswellic-acid-in-osteoarthritis-a-comparative-randomized-double-blind-placebo-controlled-study
#20
RANDOMIZED CONTROLLED TRIAL
Armine Haroyan, Vahan Mukuchyan, Nana Mkrtchyan, Naira Minasyan, Srbuhi Gasparyan, Aida Sargsyan, Mikael Narimanyan, Areg Hovhannisyan
BACKGROUND: The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with boswellic acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). METHODS: The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial...
January 9, 2018: BMC Complementary and Alternative Medicine
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