DOCSLIB.ORG

Declarations Under Rule 4.17: (21) International Application Number

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Declarations Under Rule 4.17: (21) International Application Number ) ( (51) International Patent Classification: Declarations under Rule 4.17: A61K 33/36 (2006.01) A61P 35/02 (2006.01) — as to applicant's entitlement to apply for and be granted a A61P 35/00 (2006.01) patent (Rule 4.17(H)) (21) International Application Number: — as to the applicant's entitlement to claim the priority of the PCT/CN20 19/070 117 earlier application (Rule 4.17(iii)) — of inventorship (Rule 4.17(iv)) (22) International Filing Date: 02 January 2019 (02.01.2019) Published: — with international search report (Art. 21(3)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: PCT/CN20 18/07005 1 02 January 2018 (02.01.2018) CN PCT/CN20 18/085 190 28 April 2018 (28.04.2018) CN (71) Applicant: RUI JIN HOSPITAL, SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE [CN/CN]; 11th Building, 197 Ruijin Er Road, Shanghai 200025 (CN). (72) Inventors: LU, Min; 1lth Building, 197 Ruijin Er Road, Shanghai 200025 (CN). WU, Jiale; 11th Building, 197 Rui¬ jin Er Road, Shanghai 200025 (CN). SONG, Huaxin; 11th Building, 197 Ruijin Er Road, Shanghai 200025 (CN). (74) Agent: BEIJING DACHENG LAW OFFICES, LLP; 15th/16th Floor, Shanghai Tower, 501 YinchengRoad (M), Pudong New Area, Shanghai 200120 (CN). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (54) Title: MP53 RESCUE COMPOUNDS AND METHODS OF TREATING A P53 DISORDER (57) Abstract: Novel mp53 rescue compounds and the pharmaceutical composition, and methods of treating a p53 disorder. MP53 RESCUE COMPOUNDS AND METHODS O F TREATING A P53 DISORDER TECHNICAL FIELD [0001] Various compositions for the rescue of a mp53, various pharmaceutical composition for a p53 disorder, such as cancer, and various methods for treating the p53 disorder, are disclosed herein. CROSS REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to International Application No. PCT/CN201 8/070051 filed on January 2 , 2018, entitled “PANDA AS A NOVEL THERAPEUTIC and International Application No. PCT/CN/201 8/0851 90 filed on April 28, 2018, entitled “PANDA A S A NOVEL THERAPEUTIC,” the content of each application is incorporated herein by reference in their entirety. BACKGROUND [0003] Various compounds for rescuing mp53 and treating a p53 disorder, including cancer, and various methods of treating a p53 disorder have been proposed. Because these compounds, treatments and methods of treatments are not optimal, there is a need in the field for improved mp53 rescue compounds, treatments for a p53 disorder, and methods of treating a p53 disorder. SUMMARY [0004] W e have described herein compounds that have one or more useful characteristic(s) and can form one or more tight assodation(s) with a PANDA Pocket (each compound a “PANDA Agenf)· In certain embodiments, the PANDA Agent can regulate the level of one or more p53 target gene. Exemplary target genes include Apafl, Bax, Fas, Dr5, mir-34, Noxa, TP53AIP1, Parp, Pidd, Pig3, Puma, Siva, YWHAZ, Btg2, Cdknla, Mdm2, Tp53i3, Gadd45a, mir-34a, mir-34b/34c, Pr13, Ptprv, Raprimo, Pail, Pml, Ddb2, ErccS, Fancc, Gadd45a, Ku86, Mgmt, Mlh1, Msh2, P53r2, Polk, Xpc, Adora2b, Aldh4, Garni, Gls2, Gpx1, Lpinl, Parkin, Prkabl, Prkab2, Ptan, S∞ 1, Sasnl, Sesn2, Tigar, Tp53inp1, Tsc2, Atg10, Atg2b, Atg4a, Atg4c, Atg7, Ctsd, Ddit4, Draml, Foxo3, Laptm4a, Lkb1, Pik3r3, Prkag2, Puma, Tpp1, Tsc2, Ulk1, Ulk2, Uvrag, Vamp4, Vmp1, Bail, Cx3cl1, lcaml, irfS, lr†9, Isg15, Maspin, Mcp1, Ncf2, Pail, Tlr1-Tlr10, Tsp1, Ulbpl, Ulbp2, mir-34a, mir-200c, mir-145, mir-34a, mir-34b/34c, Notchl, combinations thereof and the like. In certain embodiments, the tight association formed by PANDA Agent and PANDA Pocket substantially stabilizes p53. Preferably, the tight association increases the Tm of p53 at least by about 0.5°C, more preferably at least by about 1°C, further preferably at least by about 2°C, further preferably at least by about 5°C, further preferably at least to about 8°C. In certain embodiments, the tight association formed by PANDA Agent and PANDA Pocket increases the population of properly folded p53 at least to about 1.5 times, preferably at least to about 3 times, more preferably at least to about 5 times, more preferably at least to about 10 times, and further preferably to about 100 times. In preferred embodiments, the increase is measured to a PAb1620 immunoprecipitation assay. [0005] In certain embodiments, the PANDA Agent includes one or more PANDA Pocket¬ binding groups capable of binding one or more amino acids on PANDA Pocket, preferably one or more cysteines, more preferably two or more cysteines, further preferably more than three cysteines, further preferably from about three cysteines to about 6 cysteines. The PANDA Pocket binding group is preferred to include metallic group(s), metalloid group(s), and other group(s) capable of binding to PANDA Pocket such as Michael acceptor(s) and thiol group(s). The PANDA Pocket-binding groups is further preferred to include one or more arsenic, antimony, and bismuth, including any analogue(s) thereof, and any combinations thereof. Exemplary PANDA Pocket-binding groups include compounds containing a 3- valence and/or 5-valence arsenic atom, a 3-valence and/or 5-valence antimony atom, a 3- valence and/or 5-valence bismuth atom, and/or a combination thereof. [0006] Exemplary embodiments of a PANDA Agent can include any one of the following Formulas l-XV. wherein: M is an atom selected from a group consisting of As, Sb, and Bi; Z is a functional group comprising a non-Carbon atom that forms a bond with M, wherein the non-Carbon atom is preferably selected from the group consisting of H, D, F, Cl, Br, I, O, S, Se, Te, Li, Na, K, Cs, Mg, Cu, Zn, Ba, Ta, W, Ag, Cd, Sn, X, B, N, P, Al, Ga, In, Tl, Ni, Si, Ge, Cr, Mn, Fe, Co, Pb, Y, La, Zr, Nb, Pr, Nd, Sm, Eu, Gd, Dy, Tb, Ho, Er, Tm, Yb, and Lu; wherein: R1 is selected from 1 to 9 X groups; R2 is selected from 1 to 7 X groups; R3 is selected from 1 to 8 X groups; and wherein each X group comprises an atom that forms a bond with M; and wherein: each of M, the non-Carbon atom, and the atom has the appropriate charge, including no charge, in the compound; each of Z and X is independently selected and can be the same or different from the other Z or X in the compound, respectively; and each of the M, non-Carbon atom and the atom can be a part of a ring member. In the preferred embodiment, the non-Carbon atom is selected from the group consisting of O, S, N, X, F, Cl, Br, I, and H. [0007] The following Equation ( 1) is an reaction for PANDA Agent. A compound containing M group with a Z 1 (a first group with the capacity to bind a first cysteine) and/or a Z2 (a second group with the capacity to bind a second cysteine) and/or a Z3 (a third group with the capacity to bind a third cysteine), Examples of Zi, Z2, and Z 3 includes O, S, N, X, F, Cl, Br, I, OH, and H. Zi, Z2, and/or Z 3 can bind to each other. M group includes for example a metal, such as an bismuth, a metalloid, such as an arsenic and an antimony, a group such as a Michael acceptor and/or a thiol, and/or any analogue with cysteine-binding ability. The PANDA Agent can undergo a hydrolysis before reacting and binding to p53 forming PANDA. In some cases, when a group cannot undergo hydrolysis, and accordingly cannot bind to a cysteine. In such cases, the remaining group(s) with cysteine binding potential binds to p53. Xi and X 2 represent any groups bound to M. X 1 and/or X2 can also be empty. X 1 and/or X2 can also be able to bind cysteine. [0008] [0009] The following Equations (2) and (3) is an exemplary reaction for a PANDA Agent with tri-cysteine binding potential. 3-valence ATO or KAsO2 undergoes hydrolysis, covalently binds to three PANDA Cysteines on p53. [0010] [0011] [0012] The following equation (4) is an exemplary reaction for a PANDA Agent with tri- cysteine binding potential. 5-valence As compound undergoes hydrolysis, covalently binds to three PANDA Cysteines on p53.
Load more

Recommended publications
  • California Tumor Tissue Registry Eighty-Eighth Semi
    CALIFORN IA TUMOR TISSUE REGISTRY EIGHTY-EIGHTH SEMI -ANNUAL SLIDE SEMINAR ON TUMORS OF THE CENTRAL NERVOUS SYSTEM MODERATOR: BERN W. SCHti THAUER, M. D. HEAD SECTION OF SURGICAL PATHOLOGY MAYO CLINIC PROFESSOR OF PATHOLOGY ROCHESTER, MINNESOTA CHAIRMAN: PHILIP VAN HALE, M. D. ASSOCIATE PATHOLOGIST HUNTINGTON MEMORIAL HOSP ITAL PASADENA, CALIFORNIA SUNDAY - JUNE 3, 1990 9:00 A.M. - 5:00 P.M. REGISTRATION: 7:30 A.M. SHERATON PLAZA LA REINA ~OTEL LOS ANGELES, CALIFORNIA (213) 642-1111 Please bring your protocol, but do not bring slides or microscopes to the meeting. CONTRIBUTOR: Bernd W. Scheithauer, M. 0. JUNE 1990 - CASE NO. 1 Rochester, Minnesota TISSUE FROM: Brain, left temporal parietal lobe ACCESSION NO. 26731 CLINICAL ABSTRACT : The patient is a 46 -year-old white ma le wh o experienced a head injury in 1960 but had no history of neurologic disturbances until 1982 at which time he noted the sudden onset of expressive aphasia. CT scan demonstrated a hypodense left temporoparietal lesion associated with a cyst. No enhancement was seen. - The patient elected to be medically observed over a five year interval, there being no intervention until symptoms interfered with his lifestyle. During that time he was maintained on phenobabital. The frequen cy of his partial complex seizures, which were characterized by expressive more than receptive aphasia, varied from one per month to six per week. They lasted from 1 to 30 minutes. No sensorimotor component was ever observed. Memory deficits followed the episodes. The first evidence of tumor enhancement was noted in 1984 and was seen to be somewhat more extensive in a 1986 study.
    [Show full text]
  • Enteric Peripheral Neuroblastoma in a Calf
    NOTE Pathology Enteric peripheral neuroblastoma in a calf Yusuke SAKAI1)*, Masato HIYAMA2), Saya KAGIMOTO1), Yuki MITSUI1, Miko IMAIUMI1), Takeshi OKAYAMA3), Kaori HARADONO3), Masashi SAKURAI1) and Masahiro MORIMOTO1) 1)Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi-shi, Yamaguchi 753-8515, Japan 2)Laboratory of Large Animal Clinical Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi-shi, Yamaguchi 753-8515, Japan 3)Tobu Large Animal Clinic, NOSAI Yamaguchi, 512-2 Kuhara, Shuto-cho, Iwakuni-shi, Yamaguchi 742-0417, Japan ABSTRACT. An 11-month-old female Japanese Black calf had showed chronic intestinal J. Vet. Med. Sci. symptoms. A large mass surrounding the colon wall that was continuous with the colon 81(6): 824–827, 2019 submucosa was surgically removed. After recurrence and euthanasia, a large mass in the colon region and metastatic masses in the omentum, liver, and lung were revealed at necropsy. doi: 10.1292/jvms.18-0450 Pleomorphic small cells proliferated in the mass and muscular layer of the colon. The cells were positively stained with anti-doublecortin (DCX), PGP9.5, nestin, and neuron specific enolase (NSE). Thus, the diagnosis of peripheral neuroblastoma was made. This is the first report of enteric Received: 31 July 2018 peripheral neuroblastoma in animals. Also, clear DCX staining signal suggested usefulness of DCX Accepted: 31 March 2019 immunohistochemistry to differentiate the neuroblastoma from other small cell tumors in cattle. Published online in J-STAGE: cattle, doublecortin, neuronal marker, neuronal neoplasm, peripheral neuroblastoma 9 April 2019 KEY WORDS: Neuroblastoma is an embryonal neuroectodermal neoplasm with limited neuronal differentiation that arises both in the central and peripheral nervous systems [12].
    [Show full text]
  • Eyelid Conjunctival Tumors
    EYELID &CONJUNCTIVAL TUMORS PHOTOGRAPHIC ATLAS Dr. Olivier Galatoire Dr. Christine Levy-Gabriel Dr. Mathieu Zmuda EYELID & CONJUNCTIVAL TUMORS 4 EYELID & CONJUNCTIVAL TUMORS Dear readers, All rights of translation, adaptation, or reproduction by any means are reserved in all countries. The reproduction or representation, in whole or in part and by any means, of any of the pages published in the present book without the prior written consent of the publisher, is prohibited and illegal and would constitute an infringement. Only reproductions strictly reserved for the private use of the copier and not intended for collective use, and short analyses and quotations justified by the illustrative or scientific nature of the work in which they are incorporated, are authorized (Law of March 11, 1957 art. 40 and 41 and Criminal Code art. 425). EYELID & CONJUNCTIVAL TUMORS EYELID & CONJUNCTIVAL TUMORS 5 6 EYELID & CONJUNCTIVAL TUMORS Foreword Dr. Serge Morax I am honored to introduce this Photographic Atlas of palpebral and conjunctival tumors,which is the culmination of the close collaboration between Drs. Olivier Galatoire and Mathieu Zmuda of the A. de Rothschild Ophthalmological Foundation and Dr. Christine Levy-Gabriel of the Curie Institute. The subject is now of unquestionable importance and evidently of great interest to Ophthalmologists, whether they are orbital- palpebral specialists or not. Indeed, errors or delays in the diagnosis of tumor pathologies are relatively common and the consequences can be serious in the case of malignant tumors, especially carcinomas. Swift diagnosis and anatomopathological confirmation will lead to a treatment, discussed in multidisciplinary team meetings, ranging from surgery to radiotherapy.
    [Show full text]
  • Apocrine Hidrocystoma: a Slowly Growing Postauricular Translucent Nodule
    Volume 27 Number 1| January 2021 Dermatology Online Journal || Photo Vignette 27(1):16 Apocrine hidrocystoma: a slowly growing postauricular translucent nodule Karan Pandher1 BS, Felipe B Cerci2,3 MD MSc, Stanislav N Tolkachjov4 MD Affiliations: 1Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA, 2Department of Dermatology. Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil, 3Clínica Cepelle. Curitiba, Brazil, 4Epiphany Dermatology, Dallas, Texas, USA Corresponding Author: Stanislav N Tolkachjov MD, Epiphany Dermatology, 1640 FM 544, Suite 100, The Colony, TX 75056, Tel: 972-712- 3131, Email: [email protected] importance of histopathological examination of Abstract cystic tumors on the periauricular area. Apocrine hidrocystoma is a benign, cystic proliferation of the apocrine sweat gland that may present commonly on sun-exposed areas of the head Case Synopsis and neck. However, given its location and features, A middle-aged previously healthy woman presented apocrine hidrocystomas may often be confused with with an asymptomatic right postauricular lesion, that malignant tumors such as basal cell carcinomas or primary cutaneous mucinous carcinomas. Herein, we progressed to a nodule over 10 years (Figure 1A). present an unusual case of an apocrine hidrocystoma Physical examination demonstrated a translucent, presenting in the postauricular region and highlight blue-gray nodule with three rounded projections the importance of histopathological examination of and a fibroelastic consistency in the right cystic tumors on the periauricular area. postauricular region measuring 2.3×2cm in diameter. The well-defined nodule was not adherent to deep planes. A similar papule was present Keywords: apocrine hidrocystoma, dermatology, superiorly.
    [Show full text]
  • A Molecular Target for Human Glioblastoma
    Kuan et al. BMC Cancer 2010, 10:468 http://www.biomedcentral.com/1471-2407/10/468 RESEARCH ARTICLE Open Access MRP3: a molecular target for human glioblastoma multiforme immunotherapy Chien-Tsun Kuan1,2*†, Kenji Wakiya1,2†, James E Herndon II2, Eric S Lipp2, Charles N Pegram1,2, Gregory J Riggins3, Ahmed Rasheed1, Scott E Szafranski1, Roger E McLendon1,2, Carol J Wikstrand4, Darell D Bigner1,2* Abstract Background: Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular therapeutic target that is expressed by GBM: human multidrug-resistance protein 3 (MRP3). Methods: We investigated MRP3 by genetic and immunohistochemical (IHC) analysis of human gliomas to determine the incidence, distribution, and localization of MRP3 antigens in GBM and their potential correlation with survival. To determine MRP3 mRNA transcript and protein expression levels, we performed quantitative RT-PCR, raising MRP3-specific antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients. We used univariate and multivariate analyses to assess the correlation of RNA expression and IHC of MRP3 with patient survival, with and without adjustment for age, extent of resection, and KPS. Results: Real-time PCR results from 67 GBM biopsies indicated that 59/67 (88%) samples highly expressed MRP3 mRNA transcripts, in contrast with minimal expression in normal brain samples. Rabbit polyvalent and murine monoclonal antibodies generated against an extracellular span of MRP3 protein demonstrated reactivity with defined MRP3-expressing cell lines and GBM patient biopsies by Western blotting and FACS analyses, the latter establishing cell surface MRP3 protein expression.
    [Show full text]
  • Abnormality of the Middle Phalanx of the 4Th Toe Abnormality of The
    Glucocortocoid-insensitive primary hyperaldosteronism Absence of alpha granules Dexamethasone-suppresible primary hyperaldosteronism Abnormal number of alpha granules Primary hyperaldosteronism Nasogastric tube feeding in infancy Abnormal alpha granule content Poor suck Nasal regurgitation Gastrostomy tube feeding in infancy Abnormal alpha granule distribution Lumbar interpedicular narrowing Secondary hyperaldosteronism Abnormal number of dense granules Abnormal denseAbnormal granule content alpha granules Feeding difficulties in infancy Primary hypercorticolismSecondary hypercorticolism Hypoplastic L5 vertebral pedicle Caudal interpedicular narrowing Hyperaldosteronism Projectile vomiting Abnormal dense granules Episodic vomiting Lower thoracicThoracolumbar interpediculate interpediculate narrowness narrowness Hypercortisolism Chronic diarrhea Intermittent diarrhea Delayed self-feeding during toddler Hypoplastic vertebral pedicle years Intractable diarrhea Corticotropin-releasing hormone Protracted diarrhea Enlarged vertebral pedicles Vomiting Secretory diarrhea (CRH) deficient Adrenocorticotropinadrenal insufficiency (ACTH) Semantic dementia receptor (ACTHR) defect Hypoaldosteronism Narrow vertebral interpedicular Adrenocorticotropin (ACTH) distance Hypocortisolemia deficient adrenal insufficiency Crohn's disease Abnormal platelet granules Ulcerative colitis Patchy atrophy of the retinal pigment epithelium Corticotropin-releasing hormone Chronic tubulointerstitial nephritis Single isolated congenital Nausea Diarrhea Hyperactive bowel
    [Show full text]
  • Oculoplastic Aspects of Ocular Oncology
    Eye (2013) 27, 199–207 & 2013 Macmillan Publishers Limited All rights reserved 0950-222X/13 www.nature.com/eye Oculoplastic aspects C Rene CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM of ocular oncology Abstract represents a significant proportion of the oculoplastic surgeon’s workload. In this review, It is estimated that 5–10% of all cutaneous the features of periocular skin cancer are malignancies involve the periocular region presented together with a discussion of the and management of periocular skin cancers treatment modalities. account for a significant proportion of the oculoplastic surgeon’s workload. Epithelial tumours are most frequently encountered, Diagnosing malignant eyelid disease including basal cell carcinoma, squamous cell carcinoma, and sebaceous gland Although malignant eyelid disease is usually carcinoma, in decreasing order of frequency. easy to diagnose on the basis of the history and Non-epithelial tumours, such as cutaneous clinical signs identified on careful examination melanoma and Merkel cell carcinoma, rarely (Table 1), differentiating between benign and involve the ocular adnexae. Although malignant periocular skin lesions can be non-surgical treatments for periocular challenging because malignant lesions malignancies are gaining in popularity, occasionally masquerade as benign pathology. surgery remains the main treatment modality For instance, a cystic basal cell carcinoma (BCC) 4,5 and has as its main aims tumour clearance, can resemble a hidrocystoma or sebaceous restoration of the eyelid function, protection gland carcinoma (SGC) classically mimics a 6,7 of the ocular surface, and achieving a good chalazion. Conversely, a benign lesion such as cosmetic outcome. The purpose of this article a pigmented hidrocystoma may be mistaken for 8 is to review the management of malignant a malignant melanoma.
    [Show full text]
  • 2016 Essentials of Dermatopathology Slide Library Handout Book
    2016 Essentials of Dermatopathology Slide Library Handout Book April 8-10, 2016 JW Marriott Houston Downtown Houston, TX USA CASE #01 -- SLIDE #01 Diagnosis: Nodular fasciitis Case Summary: 12 year old male with a rapidly growing temple mass. Present for 4 weeks. Nodular fasciitis is a self-limited pseudosarcomatous proliferation that may cause clinical alarm due to its rapid growth. It is most common in young adults but occurs across a wide age range. This lesion is typically 3-5 cm and composed of bland fibroblasts and myofibroblasts without significant cytologic atypia arranged in a loose storiform pattern with areas of extravasated red blood cells. Mitoses may be numerous, but atypical mitotic figures are absent. Nodular fasciitis is a benign process, and recurrence is very rare (1%). Recent work has shown that the MYH9-USP6 gene fusion is present in approximately 90% of cases, and molecular techniques to show USP6 gene rearrangement may be a helpful ancillary tool in difficult cases or on small biopsy samples. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 5th edition. Mosby Elsevier. 2008. Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, Ye Y, Lau AW, Wang X, Oliveira AM. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011 Oct;91(10):1427-33. Amary MF, Ye H, Berisha F, Tirabosco R, Presneau N, Flanagan AM. Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool. Virchows Arch. 2013 Jul;463(1):97-8. CONTRIBUTED BY KAREN FRITCHIE, MD 1 CASE #02 -- SLIDE #02 Diagnosis: Cellular fibrous histiocytoma Case Summary: 12 year old female with wrist mass.
    [Show full text]
  • Rotana Alsaggaf, MS
    Neoplasms and Factors Associated with Their Development in Patients Diagnosed with Myotonic Dystrophy Type I Item Type dissertation Authors Alsaggaf, Rotana Publication Date 2018 Abstract Background. Recent epidemiological studies have provided evidence that myotonic dystrophy type I (DM1) patients are at excess risk of cancer, but inconsistencies in reported cancer sites exist. The risk of benign tumors and contributing factors to tu... Keywords Cancer; Tumors; Cataract; Comorbidity; Diabetes Mellitus; Myotonic Dystrophy; Neoplasms; Thyroid Diseases Download date 07/10/2021 07:06:48 Link to Item http://hdl.handle.net/10713/7926 Rotana Alsaggaf, M.S. Pre-doctoral Fellow - Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH PhD Candidate – Department of Epidemiology & Public Health, University of Maryland, Baltimore Contact Information Business Address 9609 Medical Center Drive, 6E530 Rockville, MD 20850 Business Phone 240-276-6402 Emails [email protected] [email protected] Education University of Maryland – Baltimore, Baltimore, MD Ongoing Ph.D. Epidemiology Expected graduation: May 2018 2015 M.S. Epidemiology & Preventive Medicine Concentration: Human Genetics 2014 GradCert. Research Ethics Colorado State University, Fort Collins, CO 2009 B.S. Biological Science Minor: Biomedical Sciences 2009 Cert. Biomedical Engineering Interdisciplinary studies program Professional Experience Research Experience 2016 – present Pre-doctoral Fellow National Cancer Institute, National Institutes
    [Show full text]
  • A Giant Apocrine Hidrocystoma of the Trunk
    Volume 23 Number 9 | September 2017 Dermatology Online Journal || Photo Vignette DOJ 23 (9): 19 A giant apocrine hidrocystoma of the trunk Caitlin May1 MD, Oliver Chang2 MD, Nicholas Compton1 MD Affiliations: 1Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 2VA Puget Sound Health Care System, Seattle, Washington Corresponding Author: Caitlin May MD, 1959 Northeast Pacific Street, Box 356524, Seattle, WA 98195, Tel: (206) 598-4067, Fax: (206) 598- 4768, Email: [email protected] Abstract reported that the mass started out the size of a “wart,” which slowly grew in size over a 6-month period Hidrocystomas are benign cysts that typically present prior to evaluation. The mass was asymptomatic. as translucent, bluish dermal nodules on the face and He denied any drainage from the mass. He had no are rarely > 1 cm in size. They are classically categorized new neurologic symptoms in the lower extremities. as eccrine or apocrine based on histologic features. We The patient’s health was otherwise declining, with present a rare case of a giant apocrine hidrocystoma a weight loss of over 100 pounds since 2011 and of the trunk, demonstrating that, although a rare several recent hospitalizations for COPD and CHF variant, apocrine hidrocystomas can present both off exacerbations. The patient reported no personal or the head and neck, and can be significantly larger in family history of skin or soft tissue malignancy. size than previously reported. Examination demonstrated a 5.5 x 5.5 cm mobile, non-tender, fluctuant mass on the right lower back. Keywords: hidrocystoma, cyst There was variation of overlying epidermal coloration, with a purplish-red hue along the periphery and a hypopigmented appearance centrally (Figure 1).
    [Show full text]
  • Sinonasal Tumors
    Prepared by Kurt Schaberg Sinonasal/Nasopharyngeal Tumors Benign Sinonasal Papillomas aka Schneiderian papilloma Morphology Location Risk of Molecular transformation Exophytic Exophytic growth; Nasal Very low risk Low-risk HPV immature squamous epithelium septum subtypes Inverted Inverted ‘‘ribbonlike’’ growth; Lateral Low to EGFR immature squamous epithelium; wall and Intermediate risk mutations or transmigrating intraepithelial sinuses low-risk HPV neutrophilic inflammation subtypes Oncocytic Exophytic and endophytic growth; Lateral Low to KRAS multilayered oncocytic epithelium; wall and intermediate microcysts and intraepithelial sinuses neutrophilic microabscesses Modified from: Weindorf et al. Arch Pathol Lab Med—Vol 143, November 2019 Oncocytic Sinonasal Papilloma Note the abundant oncocytic epithelium with numerous neutrophils Inverted Sinonasal Papilloma Note the inverted, “ribbon-like” growth Respiratory Epithelial Adenomatoid Hamartoma aka “REAH” Sinonasal glandular proliferation arising from the surface epithelium (i.e., in continuity with the surface). Invaginations of small to medium-sized glands surrounded by hyalinized stroma with characteristic thickened, eosinophilic basement membrane Exists on a spectrum with seromucinous hamartoma, which has smaller glands. Should be able to draw a circle around all of the glands though, if too confluent → consider a low-grade adenocarcinoma Inflammatory Polyp Surface ciliated, sinonasal mucosa, possibly with squamous metaplasia. Edematous stroma (without a proliferation of seromucinous glands). Mixed inflammation (usu. Lymphocytes, plasma cells, and eosinophils) Pituitary adenoma Benign anterior pituitary tumor Although usually primary to sphenoid bone, can erode into nasopharynx or be ectopic Can result in endocrine disorders, such as Cushing’s disease or acromegaly. Solid, nested, or trabecular growth of epithelioid cells with round nuclei and speckled chromatin and eosinophilic, granular chromatin. Express CK, and neuroendocrine markers.
    [Show full text]
  • Statistical Analysis Plan
    Cover Page for Statistical Analysis Plan Sponsor name: Novo Nordisk A/S NCT number NCT03061214 Sponsor trial ID: NN9535-4114 Official title of study: SUSTAINTM CHINA - Efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin in subjects with type 2 diabetes Document date: 22 August 2019 Semaglutide s.c (Ozempic®) Date: 22 August 2019 Novo Nordisk Trial ID: NN9535-4114 Version: 1.0 CONFIDENTIAL Clinical Trial Report Status: Final Appendix 16.1.9 16.1.9 Documentation of statistical methods List of contents Statistical analysis plan...................................................................................................................... /LQN Statistical documentation................................................................................................................... /LQN Redacted VWDWLVWLFDODQDO\VLVSODQ Includes redaction of personal identifiable information only. Statistical Analysis Plan Date: 28 May 2019 Novo Nordisk Trial ID: NN9535-4114 Version: 1.0 CONFIDENTIAL UTN:U1111-1149-0432 Status: Final EudraCT No.:NA Page: 1 of 30 Statistical Analysis Plan Trial ID: NN9535-4114 Efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin in subjects with type 2 diabetes Author Biostatistics Semaglutide s.c. This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant parties.This
    [Show full text]