DOCSLIB.ORG

Genitourinary PAX8

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genitourinary PAX8 174A ANNUAL MEETING ABSTRACTS RMC and 19/21 (90%) of CDC cases. In contrast, 31/34 (91%) UUC were negative for Genitourinary PAX8. p63: p63 was positive in 7/12 (58%) RMC and in 3/21 (14%) CDC. Staining was focal in 6/7 RMC and strong in 4/7. Almost all (97%) UUC were p63 positive 767 Histopathologic Features of Bilateral Renal Cell Carcinomas: A (moderate/strong and multifocal/diffuse in 80% of cases). The one p63 negative UUC Study of 24 Cases was a microinvasive high grade tumor and was also negative for PAX8. J Abdelsayed, JY Ro, LD Truong, AG Ayala, SS Shen. The Methodist Hospital and Weill Conclusions: We suggest a binary panel of PAX8 and p63 as an aid in the differential Medical College of Cornell University, Houston, TX. diagnosis of high grade renal sinus epithelial neoplasms. (PAX8+/p63+) profile Background: The incidence of bilateral renal cell carcinoma (bRCC) has been reported supported the dx of RMC with a sensitivity of 58.3% and specificity of 89%. (PAX8+/ to vary from 1.5% to 11%. Clear understanding of the clinicopathologic features of p63-) profile supported the diagnosis of CDC with a sensitivity of 85.7% and a specificity bRCCs including the distinction between synchronous and metachronous tumors has of 89%. Finally (PAX8-/p63+) profile supported the diagnosis of UUC with a sensitivity important implications in patients’ management and follow up. The purpose of this study of 88% and a specificity of 100%. The concomitant expression of p63 and PAX8 in RMC is to summarize the clinicopathologic features of bRCCs and compare them with those seen in our study further suggests an intermediate phenotype between renal tubular and of unilateral renal cell carcinomas (uRCCs). a urothelial differentiation in RMC. Design: Of the 1230 patients treated at our hospital for RCC from 1990 to 2006, 24 (2.0%) were found to have bRCCs. The clinicopathologic features of these patients 770 PAX-8 Expression in Urothelial Neoplasia – An Immunohistochemical were reviewed and compared with those of unilateral RCCs. Study of 236 Cases Results: There were no significant differences in gender or age (59.7 vs. 60.3 years) R Albadine, L Schultz, DA Fajardo, R Sharma, PB Illei, S Jadallah, JI Epstein, GJ between patients with bRCCs or uRCCs. Of the 24 bRCCs, 13 were synchronous and Netto. Johns Hopkins University, Baltimore, MD. 11 were metachronous tumors (with an average of 22.6 months after 1st tumor). Three Background: PAX-8 is a transcription factor crucial for lineage commitment in thyroid, patients had Von Hippel Lindau (VHL) syndrome. Overall, 21 of 24 bRCCs (87.5%) Mullerian duct and nephric development. For its role in ontogenesis and oncogenesis had the same histology, while in 3 patients with metachronous tumors, the 1st tumor was in the genitourinary tract, PAX-8 has recently gained great utility as a marker of renal a clear RCC, and the contralateral tumor was a papillary RCC. The incidence of clear and ovarian lineage. In the current study, we investigate PAX-8 expression in a large cell, papillary, and chromophobe RCC was 54.1%, 41.6%, and 4.2% respectively for cohort of invasive and non-invasive urothelial neoplasms of upper and lower urinary bilateral RCC, compared to 77.2%, 15.2%, and 5.6% for unilateral RCC. Six of 13 pts tract, to further validate its utility in resolving the differential diagnosis of urothelial with synchronous tumors died within an average time of 22.6 month, contrasting with vs renal differentiation. 2 of 11 patients with metachronous tumors died at an average time of 102.8 month. Design: Tissue microarrays (TMA) were constructed from archival tissues of urothelial Conclusions: In this series, the incidence of bilateral RCC was 2.0%. VHL disease neoplasms retrieved from our institution (1985-2005). The cohort of 236 tumors included accounted for 14.2% of bRCC. The incidence of papillary RCC in patients with bRCC 200 bladder tumors: 6 Papillary Urothelial Neoplasm of Low Malignant Potential was much higher than in patients with uRCCs (41.6% vs. 15.0%). Our study also (PUNLMP), 43 non-invasive urothelial carcinoma (10 high grade) and 151 invasive indicates that patients with synchronous tumors have worse survival than patients with urothelial carcinoma (UrCa). The cohort also included 36 urothelial carcinoma of the metachronous tumors. upper urinary tract (UUC), including 2 non-invasive tumors. Triplicate tumor samples were spotted from each case. Immunohistochemistry for PAX-8 was performed using 768 Unique Morphologic Characteristics of High Grade Urothelial standard protocol and appropriate controls. Tumors were evaluated for extent of nuclear Carcinoma with Fibroblast Growth Factor Receptor-3 (FGFR3) Gene staining, categorized as focal (<25%), multifocal (25-75%) or diffuse (>75%) and Mutations assigned an incremental 0 to 3+ intensity score. The UUC subset of the cohort was further HA Al-Ahmadie, O Lin, GV Iyer, A Heguy, A Gopalan, SW Fine, SK Tickoo, AJ Hanrahan, evaluated for p63 immunostaining (NeoMarkers), using a similar approach. DF Bajorin, VE Reuter, DB Solit, MI Milowsky. Memorial Sloan-Kettering Cancer Results: Overall, 224/236 (95%) of urothelial neoplasms were negative for PAX-8. All Center, New York, NY. 6 (100%) PUNLMP and 151 (100%) invasive UrCa of the bladder were negative for Background: FGFR3 gene mutations in urothelial carcinoma (UC) demonstrate a PAX-8. PAX-8 staining was encountered in 7/43 (16%) non-invasive bladder UrCa. predilection for low grade and low stage tumors. Mutations in high grade UC are less In UUC, 3 (8%) invasive tumors were positive for PAX-8, all with weak/moderate common, however, as a receptor tyrosine kinase; FGFR3 may represent a potential intensity (1+/2+). Both cases of non-invasive UUC were negative for the PAX-8. p63 therapeutic target. We analyzed a large cohort of high grade UC for FGFR3 gene was positive in 33/36 (92%) UUC. The 3 negative cases included 2 non-invasive and mutational status and histopathologic characteristics. 1 pT1 tumor and all were also negative for PAX-8. Design: DNA extraction, whole genome amplification and Sanger Sequencing for Conclusions: For all practical purposes, urothelial neoplasms of the bladder lack PAX-8 FGFR3 gene mutations in exons 7, 10 and 15 was performed on frozen tumor and expression. All invasive UrCa of bladder origin were negative for PAX-8. Although normal tissue samples from 137 cystectomy specimens with invasive or refractory high rare PAX-8 positivity was encountered in non invasive tumors, their urothelial nature grade UC. All putative mutations were confirmed by a second PCR and sequencing is evident by their architecture. In UUC, where the differential diagnosis includes RCC, reaction, in parallel with amplification and sequencing of matched normal tissue DNA. PAX-8 was rarely expressed by invasive UUC (8%), the urothelial nature of the latter Detailed morphologic assessment of all cases was undertaken, including slides from subset of cases can be resolved by their co-expression of p63. corresponding transurethral resections when necessary. Results: FGFR3 gene mutations were detected in 16 of 137 (12%) cases (pTa, 1; pT1, 771 mTOR Pathway Alterations in Chromophobe Renal Cell Carcinoma 5; pT2, 4; pT3, 6). All were confirmed somatic missense mutations including S249C (RCC) (9), R248C (3), G370C (2), S371C (1) and Y373C (1). Besides the invasive component, R Albadine, L Schultz, J Hicks, AM Demarzo, P Argani, M Carducci, R Pili, GJ Netto. 15 of 16 FGFR3-mutated tumors (94%) displayed a distinct non invasive papillary Johns Hopkins University, Baltimore. component characterized by long, slender branching papillary formations, lined by Background: Dysregulation of mTOR pathway has been demonstrated in several polygonal cells with distinct cell borders and clear to eosinophilic cytoplasm. The types of malignancies. mTOR pathway activation interacts with effectors of cell cycle nuclei were variable in size with vesicular chromatin and irregular “wrinkled” nuclear progression and ultimately regulates protein translation and cell proliferation. Tumor membrane attaining a “koilocytoid” appearance. In 10 cases (63%), a component of hypoxia modulates mTOR pathway through HIF1α accumulation. Agents targeting low grade morphology was also demonstrable. mTOR are in various stages of clinical development. Here, we assess the status of Conclusions: 1. We confirmed that FGFR3 gene mutations are present in a small but several mTOR pathway components in Chormophobe RCC. significant proportion of high grade UC. 2. FGFR3 gene mutations confer unique Design: Standard immunohistochemical analysis was performed for PTEN, phos Akt, histopathologic features. 3. Identification of these histopathologic features may help p27, c-MYC, 4-EBP1, phos S6, and HIF1α using tissue microarrays constructed from to select patients for targeted therapy. 33 primary Chormophobe RCC (60% pT1 and 40% pT2-3) treated at our hospital (2004- 2006). Triplicate tumor samples and paired benign renal tissue controls were spotted 769 PAX8 (+)/p63 (+) Immunostaining Pattern in Renal Medullary in every case. Nuclear and or cytoplasmic expression was assessed for each marker as Carcinoma (RMC): An Intermediate Phenotype between Urothelial the percentage of positive cells (extent) and intensity of staining. A final H-score was Carcinoma of Upper Urinary Tract (UUC) and Collecting Ducts Carcinoma calculated in each tumor as the product of intensity x extent, and was correlated with (CDC) clinico-pathological parameters. R Albadine, L Schultz, A Billis, H Ellwood, DE Baydar, A Garvin, JI Epstein, P Argani, Results: In our cohort, M:F ratio was 1.13 and mean age at diagnosis was 59.7 years. G Netto. Johns Hopkins University, Baltimore; UNICAMP State University, Campinas, Mean tumor size was 4.7 cm. Three cases had multifocal disease. Mean length of Brazil; Hacettepe, Ankara, Turkey. follow-up was 28 months (range: 2-61). A 97% disease free survival rate was observed Background: Renal Medullary carcinoma (RMC) is a rare highly aggressive tumor during follow up.
Load more

Recommended publications
  • Aberrant Expression of ZIP and Znt Zinc Transporters in Urotsa Cells Transformed to Malignant Cells by Cadmium
    Article Aberrant Expression of ZIP and ZnT Zinc Transporters in UROtsa Cells Transformed to Malignant Cells by Cadmium Soisungwan Satarug 1,2,*, Scott H. Garrett 2, Seema Somji 2, Mary Ann Sens 2 and Donald A. Sens 2 1 Kidney Disease Research Collaborative, Centre for Health Service Research, The University of Queensland Translational Research Institute, Woolloongabba, Brisbane 4102, Australia 2 Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA; [email protected] (S.H.G.); [email protected] (S.S.); [email protected] (M.A.S.); [email protected] (D.A.S.) * Correspondence: [email protected] Abstract: Maintenance of zinc homeostasis is pivotal to the regulation of cell growth, differentiation, apoptosis, and defense mechanisms. In mammalian cells, control of cellular zinc homeostasis is through zinc uptake, zinc secretion, and zinc compartmentalization, mediated by metal transporters of the Zrt-/Irt-like protein (ZIP) family and the Cation Diffusion Facilitators (CDF) or ZnT family. We quantified transcript levels of ZIP and ZnT zinc transporters expressed by non-tumorigenic UROtsa cells and compared with those expressed by UROtsa clones that were experimentally transformed to cancer cells by prolonged exposure to cadmium (Cd). Although expression of the ZIP8 gene in parent UROtsa cells was lower than ZIP14 (0.1 vs. 83 transcripts per 1000 β-actin transcripts), an increased expression of ZIP8 concurrent with a reduction in expression of one or two zinc influx transporters, namely ZIP1, ZIP2, and ZIP3, were seen in six out of seven transformed UROtsa clones.
    [Show full text]
  • Interactions of Zinc with the Intestinal Epithelium - Effects On
    Aus dem Institut für Veterinär-Physiologie des Fachbereichs Veterinärmedizin der Freien Universität Berlin Interactions of zinc with the intestinal epithelium - effects on transport properties and zinc homeostasis Inaugural-Dissertation zur Erlangung des Grades eines Doktors der Veterinärmedizin an der Freien U niversität Berlin vorgelegt von Eva-Maria Näser, geb. Gefeller Tierärztin aus Kassel Berlin 2015 Journal-Nr.: 3813 Gefördert durch die Deutsche Forschungsgemeinschaft und die H.W. Schaumann Stiftung Gedruckt mit Genehmigung des Fachbereichs Veterinärmedizin der Freien Universität Berlin Dekan: Univ.-Prof. Dr. Jürgen Zentek Erster Gutachter: Univ.-Prof. Dr. Jörg Rudolf Aschenbach Zweiter Gutachter: Prof. Dr. Holger Martens Dritter Gutachter: Prof. Dr. Robert Klopfleisch Deskriptoren (nach CAB-Thesaurus): pigs, weaning, zinc, intestines, epithelium, jejunum, ion transport Tag der Promotion: 15.09.2015 Bibliografische Information der Deutschen Nationalbibliothek Die Deutsche Nationalbibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie; detaillierte bibliografische Daten sind im Internet über <http://dnb.ddb.de> abrufbar. ISBN: 978-3-86387-656-2 Zugl.: Berlin, Freie Univ., Diss., 2015 Dissertation, Freie Universität Berlin D 188 Dieses Werk ist urheberrechtlich geschützt. Alle Rechte, auch die der Übersetzung, des Nachdruckes und der Vervielfältigung des Buches, oder Teilen daraus, vorbehalten. Kein Teil des Werkes darf ohne schriftliche Genehmigung des Verlages in irgendeiner Form reproduziert oder unter Verwendung elektronischer Systeme verarbeitet, vervielfältigt oder verbreitet werden. Die Wiedergabe von Gebrauchsnamen, Warenbezeichnungen, usw. in diesem Werk berechtigt auch ohne besondere Kennzeichnung nicht zu der Annahme, dass solche Namen im Sinne der Warenzeichen- und Markenschutz-Gesetzgebung als frei zu betrachten wären und daher von jedermann benutzt werden dürfen. This document is protected by copyright law.
    [Show full text]
  • Targeting an Nrf2/G6pdh Pathway to Reverse Multi-Drug
    TARGETING AN NRF2/G6PDH PATHWAY TO REVERSE MULTI-DRUG RESISTANCE IN DIFFUSE LARGE B-CELL LYMPHOMA A Dissertation by SEYEDHOSSEIN MOUSAVIFARD Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Steve Maxwell Committee Members, James C. Sacchettini Raquel Sitcheran David W. Threadgill Warren Zimmer Head of Program, Warren Zimmer May 2017 Major Subject: Medical Sciences Copyright 2017 Seyed Hossein Mousavi-Fard ABSTRACT A leading cause of mortality in diffuse large B-cell lymphoma (DLBCL) patients is the development of resistance to the CHOP regimen, the anthracycline-based chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. Our first objective of this work was to investigate the impact of Nuclear factor erythroid–related factor 2 (Nrf2)/ glucose-6-phosphate dehydrogenase (G6PDH) pathway on CHOP-resistance in DLBCL cell lines. We provide evidence here that a Nrf2/G6PDH pathway plays a role in mediating CHOP resistance in DLBCL. We found that CHOP-resistant DLBCL cells expressed both higher Nrf2 and G6PDH activities and lower reactive oxygen (predominantly superoxide) levels than CHOP- sensitive cells. We hypothesized that increased activity of the Nrf2/G6PDH pathway leads to higher GSH production, a more reduced state (lower ROS), and CHOP-resistance. In support of our hypothesis, direct inhibition of G6PDH or knockdown of Nrf2/G6PDH lowered both NADPH and GSH levels, increased ROS, and reduced tolerance or CHOP-resistant cells to CHOP. We also present evidence that repeated cycles of CHOP treatment select for a small population of Nrf2High/G6PDHHigh/ROSLow cells that are more tolerant of CHOP and might be responsible for the emergence of chemoresistant tumors.
    [Show full text]
  • Genitourinary Pathology (Including Renal Tumors)
    LABORATORY INVESTIGATION THE BASIC AND TRANSLATIONAL PATHOLOGY RESEARCH JOURNAL LI VOLUME 99 | SUPPLEMENT 1 | MARCH 2019 2019 ABSTRACTS GENITOURINARY PATHOLOGY (INCLUDING RENAL TUMORS) (776-992) MARCH 16-21, 2019 PLATF OR M & 2 01 9 ABSTRACTS P OSTER PRESENTATI ONS EDUCATI ON C O M MITTEE Jason L. Hornick , C h air Ja mes R. Cook R h o n d a K. Y a nti s s, Chair, Abstract Revie w Board S ar a h M. Dr y and Assign ment Co m mittee Willi a m C. F a q ui n Laura W. La mps , Chair, C ME Subco m mittee C ar ol F. F ar v er St e v e n D. Billi n g s , Interactive Microscopy Subco m mittee Y uri F e d ori w Shree G. Shar ma , Infor matics Subco m mittee Meera R. Ha meed R aj a R. S e et h al a , Short Course Coordinator Mi c h ell e S. Hir s c h Il a n W ei nr e b , Subco m mittee for Unique Live Course Offerings Laksh mi Priya Kunju D a vi d B. K a mi n s k y ( Ex- Of ici o) A n n a M ari e M ulli g a n Aleodor ( Doru) Andea Ri s h P ai Zubair Baloch Vi nita Parkas h Olca Bast urk A nil P ar w a ni Gregory R. Bean , Pat h ol o gist-i n- Trai ni n g D e e p a P atil D a ni el J.
    [Show full text]
  • An Analysis of Benign Human Prostate Offers Insights Into the Mechanism
    www.nature.com/scientificreports OPEN An analysis of benign human prostate ofers insights into the mechanism of apocrine secretion Received: 12 March 2018 Accepted: 22 February 2019 and the origin of prostasomes Published: xx xx xxxx Nigel J. Fullwood 1, Alan J. Lawlor2, Pierre L. Martin-Hirsch3, Shyam S. Matanhelia3 & Francis L. Martin 4 The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the diferent cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are primarily produced by apocrine secretion. Patients (n = 10) undergoing TURP were prospectively consented based on their having a low risk of harbouring CaP. Scanning electron microscopy and transmission electron microscopy was used to characterise cell types and modes of secretion. Zinc levels were determined using Inductively Coupled Plasma Mass Spectrometry. Although merocrine secretory cells were noted, the majority of secretory cells appear to be apocrine; for the frst time, we clearly show high-resolution images of the stages of aposome secretion in human prostate. We also report a previously undescribed type of epithelial cell and the frst ultrastructural image of wrapping cells in human prostate stroma. The zinc levels in the tissues examined were uniformly high and X-ray microanalysis detected zinc in merocrine cells but not in prostasomes. We conclude that a signifcant proportion of prostasomes, possibly the majority, are generated via apocrine secretion. This fnding provides an explanation as to why so many large proteins, without a signal peptide sequence, are present in the prostatic fuid. Tere are many complications associated with the prostate from middle age onwards, including benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
    [Show full text]
  • Epithelial Tissue
    Epithelial Tissue Epithelial Tissue Tissues - Introduction · a group of similar cells specialized to carry on a particular function · tissue = cells + extracellular matrix nonliving portion of a tissue that supports cells · 4 types epithelial - protection, secretion, absorption connective - support soft body parts and bind structures together muscle - movement nervous - conducts impulses used to help control and coordinate body activities Epithelial Tissues Characteristics Epithelial Classifications · free surface open to the outside or an open · classified based on shape and # of cell layers internal space (apical surface) · shape · basement membrane anchors epithelium to squamous - thin, flat cells underlying connective tissue cuboidal - cube-shaped cells columnar - tall, elongated cells · lack blood vessels · number · readily divide (ex. skin healing) simple - single layer · tightly packed with little extracellular space stratified - 2 or more layers Epithelial Locations Simple Squamous Epithelium · a single layer of thin, flattened cells · cover body surfaces, cover and line internal organs, and compose glands looks like a fried egg · easily damaged skin cells, cells that line the stomach and small intestine, inside your mouth · common at sites of filtration, diffusion, osmosis; cover surfaces · air sacs of the lungs, walls of capillaries, linings cheek cells of blood and lymph vessels intestines skin Epithelial Tissue Simple Cuboidal Epithelium Simple Columnar Epithelium · single layer of cube-shaped cells · single layer of cells
    [Show full text]
  • Poster: Publikace 2008
    Publikované Práce lékařů Šiklova Patologicko – anatomického ústavu a bioPtické laboratoře s.r.o. za rok 2008 Časopisy s „impact“ faktorem syringofibroadenoma associated with well-differentiated squamous cell 28. Kuroda N., Katto K., Yamaguchi T., Kawada T., ImamuraY., Hes O., Michal M., 42. Vazmitel M., Spagnolo D.V., Němcová J., Michal M., Kazakov D.V.: 1. Alvarado-Cabrero I., Perez-Montiel D.M., Hes, O.: Multicystic urothelial carcinoma. Am J Dermatopathol, 30, 572-574, 2008. Shuin T., Lee G.H.: Chromophobe renal cell carcinoma: Diagnostic ancillary Hidradenoma papilliferum with a ductal carcinoma in situ component. Case report and review of the literature. Am J Dermatopathol, 30, 392-394, 2008. carcinoma of the bladder with gland-like lumina and with signet-ring cells. 17. Kacerovska D., Michal M., Kreuzberg B., Mukensnabl P., Kazakov DV.: application of imprint cytology and fluorescencein situ hybridization of Acral calcified vascular leiomyoma of the skin: a rare clinicopathological chromosomes 10 and 21 in two cases of typical and eosinophilic variants. 43. Vazmitel M., Michal M., Kazakov D.V.: Merkel cell carcinoma with a A case report. Diagn Pathol, 3, 36, 2008. follicular lymphocytic infiltrate: report of two cases. Am J Dermatopathol, 2. Beneš Z., Chlumská A., Antoš Z., Kohout P., Sequens R.: Detection of variant of cutaneous vascular leiomyomas: report of 3 cases. J Amer Acad Med Mol Morphol, 41, 227-232, 2008. 29. Kuroda N., Kato K., Tamura M., Shiotsu T., Hes O., Michal M., Hagashima 30, 389-391, 2008. carcinoma by means of endoscopic cytoscopy in the area of ulcerative colitis. Dermatology, 59,1000-1004, 2008.
    [Show full text]
  • Relationship Between Neuropathic Pain and Zinc
    Global Drugs and Therapeutics Mini Review ISSN: 2398-970X Relationship between neuropathic pain and zinc ion Tomoya Kitayama* Department of Pharmacy, School of Pharmacy and Pharmaceutical Science, Mukogawa Women’s University, Japan Neuropathic pain characterized by spontaneous pain, pain zinc ion activates matrix metalloproteinases that convert pro-BDNF sensation and tactile allodynia. The disease arising from peripheral or to mature-BDNF [7]. Zinc ion ionophore pyrithione inhibits KCC2 spinal nerve injury, diabetes, or infection with herpes virus is a result activity in vitro [8]. In other word, increase of zinc ion induces of the final product of an altered peripheral, spinal, and supraspinal decrease KCC2 function. On the other hand, high synaptic zinc ion process for which the usual analgesics are not effective and novel regulated by zinc transporter-3 elevates KCC2 activity via activation analgesics are desired. of metabotropic zinc ion sensing receptor [9]. These reports suggest The past study indicated that reduction of chloride gradient that zinc ion concentration have an important relationship with across the neuronal membrane, which in turn leads to reduction of KCC2 function. Moreover, it is considered that the alteration of zinc anion reversal potential, occurred in neurons of the superficial dorsal concentration modulates pain signaling. horn following a peripheral nerve injury [1]. The mechanism of the + - We previously detected by microarray method that partial sciatic change is down-regulation of K -Cl -cotransporter-2 (KCC2), which is nerve ligation surgery induces the decreased expression of slc30a1 (zinc potassium-chloride exporter, in spinal lamina I [1]. Similarly, the anion transporter 1, ZnT1) mRNA. The down regulation of ZnT1 gene was gradient is induced by brain-derived neurotrophic factor (BDNF) in relationship with BDNF-TrkB-KCC2 cascade reaction in astrocyte neuropathic pain model animals [2].
    [Show full text]
  • The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions Of
    The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells A thesis presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Master of Science Yuli Hu April 2021 © 2021 Yuli Hu. All Rights Reserved. 2 This thesis titled The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells by YULI HU has been approved for the Department of Biological Sciences and the College of Arts and Sciences by Yang V. Li Professor of Biomedical Sciences Florenz Plassmann Dean, College of Arts and Sciences 3 Abstract YULI HU, M.S., April 2021, Biological Sciences The Effect of Acid on the Dynamics of Intracellular Zinc and the Marker Expressions of Pluripotency in Somatic Cells Director of Thesis: Yang V. Li Microenvironmental pH is one of the factors that affect the stability of zinc- protein binding. The tight binding between zinc and proteins is favored by the basic pH, whereas acidic pH favors a loose bound, and treatment of strong acid results in the dissociation of zinc. Physiologically, the stomach uses a very acidic pH to digest food which results in a high amount of soluble zinc in the stomach. Whether or not zinc co- present with acid and the effect of zinc on the gastric lining has rarely been discussed. In my experiments, acidic treatment induced the expression of a pluripotent marker in primary cultured gastric cells. It also stimulated the release of intracellular zinc, suggesting that acidic pH supported protein expression through dynamic zinc regulation.
    [Show full text]
  • A Focus on Breast Cancer
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Pharmacol Manuscript Author Ther. Author Manuscript Author manuscript; available in PMC 2017 May 01. Published in final edited form as: Pharmacol Ther. 2016 May ; 161: 79–96. doi:10.1016/j.pharmthera.2016.03.003. Emerging therapeutic targets in metastatic progression: a focus on breast cancer Zhuo Li and Yibin Kang* Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, United States Abstract Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor-intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. Keywords Breast cancer; Metastasis; Targeted therapy; Tumor microenvironment; Immunotherapy 1. Introduction The overall 5-year survival rate for breast cancer currently stands at 90% — a dramatic improvement over the 63% survival rate in the early 1960s. When stratified by stage, the 5- year survival rates have increased to 99% for localized disease and 85% for regional advanced disease, a trend that can be attributed to early diagnoses and better treatment regimens.
    [Show full text]
  • The Influence of Dietary Zinc Concentration During Periods Of
    Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2019 The influence of dietary zinc concentration during periods of rapid growth induced by ractopamine hydrochloride or dietary energy and dietary fiber content on trace mineral metabolism and performance of beef steers Remy Nicole Carmichael Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Agriculture Commons, and the Animal Sciences Commons Recommended Citation Carmichael, Remy Nicole, "The influence of dietary zinc concentration during periods of rapid growth induced by ractopamine hydrochloride or dietary energy and dietary fiber content on trace mineral metabolism and performance of beef steers" (2019). Graduate Theses and Dissertations. 17416. https://lib.dr.iastate.edu/etd/17416 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. The influence of dietary zinc concentration during periods of rapid growth induced by ractopamine hydrochloride or dietary energy and dietary fiber content on trace mineral metabolism and performance of beef steers by Remy Nicole Carmichael A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Animal Science Program of Study Committee: Stephanie Hansen, Major Professor Nicholas Gabler Olivia Genther-Schroeder Elisabeth Huff-Lonergan Daniel Loy The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation.
    [Show full text]
  • Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours
    Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours Hellquist, Henrik; Paiva-Correia, António; Vander Poorten, Vincent; Quer, Miquel; Hernandez- Prera, Juan C; Andreasen, Simon; Zbären, Peter; Skalova, Alena; Rinaldo, Alessandra; Ferlito, Alfio Published in: Advances in Therapy DOI: 10.1007/s12325-019-01007-3 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Document license: CC BY-NC Citation for published version (APA): Hellquist, H., Paiva-Correia, A., Vander Poorten, V., Quer, M., Hernandez-Prera, J. C., Andreasen, S., Zbären, P., Skalova, A., Rinaldo, A., & Ferlito, A. (2019). Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours. Advances in Therapy, 36(8), 1950-1974. https://doi.org/10.1007/s12325-019-01007-3 Download date: 01. okt.. 2021 Adv Ther (2019) 36:1950–1974 https://doi.org/10.1007/s12325-019-01007-3 ORIGINAL RESEARCH Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours Henrik Hellquist . Anto´nio Paiva-Correia . Vincent Vander Poorten . Miquel Quer . Juan C. Hernandez-Prera . Simon Andreasen . Peter Zba¨ren . Alena Skalova . Alessandra Rinaldo . Alfio Ferlito Received: May 2, 2019 / Published online: June 17, 2019 Ó The Author(s) 2019 ABSTRACT to investigate whether an accurate histological diagnosis of the 11 different types of benign Introduction: A vast increase in knowledge of epithelial salivary gland tumours is correlated to numerous aspects of malignant salivary gland any differences in their clinical behaviour. tumours has emerged during the last decade Methods: A search was performed for histolog- and, for several reasons, this has not been the ical classifications, recurrence rates and risks for case in benign epithelial salivary gland malignant transformation, treatment modali- tumours.
    [Show full text]