DOCSLIB.ORG

WO 2016/141169 Al 9 September 2016 (09.09.2016) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2016/141169 Al 9 September 2016 (09.09.2016) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/141169 Al 9 September 2016 (09.09.2016) P O P C T (51) International Patent Classification: (74) Agent: AKHAVAN, Ramin; Caris MPI, Inc., 6655 N. A61K 31/335 (2006.01) G01N 33/50 (2006.01) MacArthur Blvd., Irving, TX 75039 (US). A61K 39/395 (2006.01) G01N 33/53 (2006.01) (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) G01N 33/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C40B 30/04 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2016/020657 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 3 March 2016 (03.03.2016) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English 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, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/127,769 3 March 2015 (03.03.2015) kind of regional protection available): ARIPO (BW, GH, 62/167,659 28 May 2015 (28.05.2015) GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: CARIS MPI, INC. [US/US]; 6655 N. MacAr- TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, thur Blvd., Irving, TX 75039 (US). 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, (72) Inventors: SPETZLER, David; 6045 N. 40th St., Para LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, dise Valley, AZ 85253 (US). ABBOTT, Brian; 3300 SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Jasper Road, Great Falls, MT 59404 (US). ELLIS, Philip; GW, KM, ML, MR, NE, SN, TD, TG). 8538 W John Cabot Rd, Peoria, AZ 85382 (US). REDDY, Sandeep; 3712 Kempton Drive, Los Alamitos, CA 90720 Published: (US). — with international search report (Art. 21(3)) (54) Title: MOLECULAR PROFILING FOR CANCER 34 — 2 3 / DISPLAY . J INPUT PRINTER DEVICE EXTERNAL DATABASES y 5¾ DATABASES (57) Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for the disease, such as treatments that provide likely benefit or likely lack o of benefit for the disease. The molecular profiling can include analysis of a sequence of a nucleic acid. The invention provides a method of identifying at least one treatment associated with a cancer in a subject. In still another related aspect, the invention provides use of a reagent in carrying out the methods of the invention, and/or use of a reagent in the manufacture of a reagent or kit o for carrying out the methods of the invention. In an aspect, the invention provides a system for identifying at least one treatment as - sociated with a cancer in a subject. MOLECULAR PROFILING FOR CANCER CROSS-REFERENCE This application claims the benefit of priority to United States Provisional Patent Application Serial Nos. 62/127,769, filed on March 3, 2015, and 62/167,659, filed on May 28, 2015; all of which applications are incorporated by reference herein in their entirety. BACKGROUND [0001] Disease states in patients are typically treated with treatment regimens or therapies that are selected based on clinical based criteria; that is, a treatment therapy or regimen is selected for a patient based on the determination that t e patient has been diagnosed with a particular disease (which diagnosis has been made from classical diagnostic assays). Although the molecular mechanisms behind various disease states have been the subject of studies for years, the specific application of a diseased individual's molecular profile in determining treatment regimens and therapies for that individual has been disease specific and not widely pursued. [0002] Some treatment regimens have been determined using molecular profiling in combination with clinical characterization of a patient such as observations made by a physician (such as a code from the International Classification of Diseases, for example, and the dates such codes were determined), laboratory test results, x-rays, biopsy results, statements made by the patient, and any other medical information typically relied upon by a physician to make a diagnosis in a specific disease. However, using a combination of selection material based on molecular profiling and clinical characterizations (such as the diagnosis of a particular type of cancer) to determine a treatment regimen or therapy presents a risk that an effective treatment regimen may be overlooked for a particular individual since some treatment regimens may work well for different disease states even though they are associated with treating a particular type of disease state. [0003] Patients with refractory or metastatic cancer are of particular concern for treating physicians. The majority of patients with metastatic or refractory cancer eventually run out of treatment options or may suffer a cancer type with no real treatment options. For example, some patients have very limited options after their tumor has progressed in spite of front line, second line and sometimes third line and beyond) therapies. For these patients, molecular profiling of their cancer may provide the only viable option for prolonging life. [0004] More particularly, additional targets or specific therapeutic agents can be identified assessment of a comprehensive number of targets or molecular findings examining molecular mechanisms, genes, gene expressed proteins, and/or combinations of such in a patient's tumor. Identifying multiple agents that can treat multiple targets or underlying mechanisms would provide cancer patients with a viable therapeutic alternative on a personalized basis so as to avoid standar therapies, which may simply not work or identify therapies that would not otherwise be considered by the treating physician. [0005] There remains a need for better theranostic assessment of cancer vicitims, including molecular profiling analysis that identifies at least one individual profile to provide more informed and effective personalized treatment options, resulting in improved patient care and enhanced treatment outcomes. The present invention provides methods and systems for identifying treatments for these individuals by molecular profiling a sample from the individual. The molecular profiling can include analysis of immune modulators such as PD-1 and/or its ligand PD-L1. SUMMARY OF THE INVENTION [0006] The present invention provides methods and system for molecular profiling, using t e results from molecular profiling to identify treatments for individuals. In some embodiments, the treatments were not identified initially as a treatment for the disease or disease lineage. The molecular profiling can include analysis of a sequence of a nucleic acid. The sequence can be assessed in multiple aspects, e.g., for t e presence or absence of any detectable chromosomal or transcript abnormality. Such a chromosomal or transcript abnormality may comprise without limitation a mutation, a polymorphism, a deletion, an insertion, a substitution, a translocation, a fusion, a break, a duplication, an amplification, a repeat, a copy number variant, a DNA methylation variation, a transcript expression level, a transcript variant, and a splice variant. [0007] In an aspect, the invention provides a method of identifying at least one treatment associated with a cancer in a subject, comprising: a) determining a molecular profile for at least one sample from the subject by assessing a plurality of genes and/or gene products; and b) identifying, based on the molecular profile, at least one of: i) at least one treatment that is associated with benefit for treatment of the cancer; ii) at least one treatment that is associated with lack of benefit for treatment of the cancer; and iii) at least one treatment associated with a clinical trial. The plurality of genes and/or gene products can be chosen from amongst genes and or gene products (e.g., transcripts and proteins) with efficacy known to be related to various chemotherapeutic agents. In one non-limiting example, it may be known that an individual with a tumor that express a certain biomarker has likely benefit of a given treatment whereas an individual with a tumor that does not express that biomarker has likely lack of benefit of the treatment. For example, HER2+ tumors may respond to the anti-HER2 antibody whereas HER2- tumors would likely receive no benefit from such treatment. In another non-limiting example, a certain drug may have likely benefit from a tumor carrying a wild type gene but not effective against a tumor carrying a given mutation in the same gene. For example, tumors with EGFR wild type may be treatable with an EGFR tyrosine kinase inhibitor (TKI), such as gefitinib and erlotinib, whereas EGFR T790M mutants are resistant to such treatments. [0008] In an embodiment of the method of the invention, the cancer comprises a bladder cancer and assessing the plurality of genes and/or gene products comprises protein analysis of at least one, e.g., 1, 2, 3, 4, 5, 6, 7, 8 or 9, of ERCC1, Her2/Neu, PD-L1, PTEN, RRM1, TOP2A, TOPOl, TS, TUBB3; and/or nucleic acid analysis of at least TOP2A.
Load more

Recommended publications
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Identification of Potential Markers for Type 2 Diabetes Mellitus Via Bioinformatics Analysis
    1868 MOLECULAR MEDICINE REPORTS 22: 1868-1882, 2020 Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis YANA LU1, YIHANG LI1, GUANG LI1* and HAITAO LU2* 1Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Jinghong, Yunnan 666100; 2Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China Received March 20, 2019; Accepted January 20, 2020 DOI: 10.3892/mmr.2020.11281 Abstract. Type 2 diabetes mellitus (T2DM) is a multifactorial and cell proliferation’. These candidate genes were also involved in multigenetic disease, and its pathogenesis is complex and largely different signaling pathways associated with ‘PI3K/Akt signaling unknown. In the present study, microarray data (GSE201966) of pathway’, ‘Rap1 signaling pathway’, ‘Ras signaling pathway’ β-cell enriched tissue obtained by laser capture microdissection and ‘MAPK signaling pathway’, which are highly associated were downloaded, including 10 control and 10 type 2 diabetic with the development of T2DM. Furthermore, a microRNA subjects. A comprehensive bioinformatics analysis of microarray (miR)-target gene regulatory network and a transcription data in the context of protein-protein interaction (PPI) networks factor-target gene regulatory network were constructed based was employed, combined with subcellular location information on miRNet and NetworkAnalyst databases, respectively. to mine the potential candidate genes for T2DM and provide Notably, hsa-miR‑192-5p, hsa-miR‑124-5p and hsa-miR‑335-5p further insight on the possible mechanisms involved. First, appeared to be involved in T2DM by potentially regulating the differential analysis screened 108 differentially expressed expression of various candidate genes, including procollagen genes.
    [Show full text]
  • Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes In
    ORIGINAL ARTICLE Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort Steven C. Elbein,1,2 Swapan K. Das,1,2 D. Michael Hallman,3 Craig L. Hanis,3 and Sandra J. Hasstedt4 OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes ype 2 diabetes is marked by a clear genetic diagnosis, and BMI. propensity, a high concordance in identical twins, tendencies for both diabetes and age of RESEARCH DESIGN AND METHODS—After removing outli- onset to be familial (1), and marked differences ers and problematic samples, we conducted linkage analysis T in prevalence among ethnic groups (2). Despite consider- using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 able evidence for a genetic predisposition, unraveling the diabetes, age of type 2 diabetes diagnosis, and BMI and nonpara- genetic etiology has been daunting, with few confirmed metric linkage analyses. Ordered subset analyses were con- genes identified from genome-wide linkage scans. Recent ducted ranking on age of type 2 diabetes diagnosis, BMI, waist successes with genome-wide association scans (3) have circumference, waist-to-hip ratio, and amount of European ad- greatly increased the number of confirmed genetic loci, mixture. Admixture mapping was conducted using 4,486 markers but these successes have been limited primarily to Cauca- not in linkage disequilibrium.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • The Adaptation and Changes of Titin System Following Exercise Training Hassan Farhadi 1 and Mir Hojjat Mosavineghad 2
    Available online a t www.pelagiaresearchlibrary.com Pelagia Research Library European Journal of Experimental Biology, 2012, 2 (4):1256-1260 ISSN: 2248 –9215 CODEN (USA): EJEBAU The adaptation and changes of titin system following exercise training Hassan Farhadi 1 and Mir Hojjat Mosavineghad 2 1Department of Physical Education and Sport Sciences, Ahar branch, Islamic Azad University, Ahar, Iran 2Department of Physical Education and Sport Sciences, khoy branch, Islamic Azad University, khoy, Iran _____________________________________________________________________________________________ ABSTRACT Titin is a large structural protein in muscle that has the ability to store elastic energy. The specific structure of titin and its elastic nature has recently become better understood. In addition, the utilization of stored elastic energy in human movement and the significant contribution of not only tendon but muscle tissue itself to this process has been re-evaluated. In this study, we reviewed the effects of exercise training on titin system (titin expression and titin- complex proteins). Keywords: Titin, titin-complex proteins, exercise training _________________________________________________________________________________________ The giant sarcomeric protein titin is 3-4 MDa and spans the sarcomere from Z-line to M-line. Titin was first discovered in 1979 by Wang et. al. (1), who initially thought that titin was a collection of polypeptides that formed one large protein. Although titin’s physical identification eluded researchers for many years, probably due to its susceptibility to proteolytic cleavage, many scientists, including Earnest Starling and A.F. Huxley, posited its existence (2). Starling and Huxley modeled their theories on the premise that something within striated muscle was regulating passive properties. This is now known to be the role of titin, which is one peptide, encoded by a single gene, TTN (2).
    [Show full text]
  • Characteristics of B Cell-Associated Gene Expression in Patients With
    MOLECULAR MEDICINE REPORTS 13: 4113-4121, 2016 Characteristics of B cell-associated gene expression in patients with coronary artery disease WENWEN YAN*, HAOMING SONG*, JINFA JIANG, WENJUN XU, ZHU GONG, QIANGLIN DUAN, CHUANGRONG LI, YUAN XIE and LEMIN WANG Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China Received May 19, 2015; Accepted February 12, 2016 DOI: 10.3892/mmr.2016.5029 Abstract. The current study aimed to identify differentially with the two other groups. Additionally the gene expression expressed B cell-associated genes in peripheral blood mono- levels of B cell regulatory genes were measured. In patients nuclear cells and observe the changes in B cell activation at with AMI, CR1, LILRB2, LILRB3 and VAV1 mRNA expres- different stages of coronary artery disease. Groups of patients sion levels were statistically increased, whereas, CS1 and IL4I1 with acute myocardial infarction (AMI) and stable angina (SA), mRNAs were significantly reduced compared with the SA and as well as healthy volunteers, were recruited into the study control groups. There was no statistically significant difference (n=20 per group). Whole human genome microarray analysis in B cell-associated gene expression levels between patients was performed to examine the expression of B cell-associated with SA and the control group. The present study identified the genes among these three groups. The mRNA expression levels downregulation of genes associated with BCRs, B2 cells and of 60 genes associated with B cell activity and regulation were B cell regulators in patients with AMI, indicating a weakened measured using reverse transcription-quantitative polymerase T cell-B cell interaction and reduced B2 cell activation during chain reaction.
    [Show full text]
  • A Population-Specific Major Allele Reference Genome from the United
    Edith Cowan University Research Online ECU Publications Post 2013 2021 A population-specific major allele efr erence genome from the United Arab Emirates population Gihan Daw Elbait Andreas Henschel Guan K. Tay Edith Cowan University Habiba S. Al Safar Follow this and additional works at: https://ro.ecu.edu.au/ecuworkspost2013 Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons 10.3389/fgene.2021.660428 Elbait, G. D., Henschel, A., Tay, G. K., & Al Safar, H. S. (2021). A population-specific major allele reference genome from the United Arab Emirates population. Frontiers in Genetics, 12, article 660428. https://doi.org/10.3389/ fgene.2021.660428 This Journal Article is posted at Research Online. https://ro.ecu.edu.au/ecuworkspost2013/10373 fgene-12-660428 April 19, 2021 Time: 16:18 # 1 ORIGINAL RESEARCH published: 23 April 2021 doi: 10.3389/fgene.2021.660428 A Population-Specific Major Allele Reference Genome From The United Arab Emirates Population Gihan Daw Elbait1†, Andreas Henschel1,2†, Guan K. Tay1,3,4,5 and Habiba S. Al Safar1,3,6* 1 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 2 Department of Electrical Engineering and Computer Science, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 3 Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates, 4 Division of Psychiatry, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, WA, Australia, 5 School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia, 6 Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias.
    [Show full text]
  • C1orf149 (MEAF6) Rabbit Polyclonal Antibody – TA333700 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA333700 C1orf149 (MEAF6) Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IHC, WB Recommended Dilution: WB, IHC Reactivity: Human Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: The immunogen for Anti-FLJ11730 Antibody: synthetic peptide directed towards the N terminal of human FLJ11730. Synthetic peptide located within the following region: HNKAAPPQIPDTRRELAELVKRKQELAETLANLERQIYAFEGSYLEDTQM Formulation: Liquid. Purified antibody supplied in 1x PBS buffer with 0.09% (w/v) sodium azide and 2% sucrose. Note that this product is shipped as lyophilized powder to China customers. Purification: Affinity Purified Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 23 kDa Gene Name: MYST/Esa1 associated factor 6 Database Link: NP_073593 Entrez Gene 64769 Human Q9HAF1 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 C1orf149 (MEAF6) Rabbit Polyclonal Antibody – TA333700 Background: The screening of cDNA expression libraries from human tumors with serum antibody (SEREX) has proven to be a powerful method for identifying the repertoire of tumor antigens recognized by the immune system of cancer patients, referred to as the cancer immunome. In this regard, cancer/testis (CT) antigens are of particular interest because of their immunogenicity and restricted expression patterns. Synoivial sarcomas are striking with regard to CT antigen expression, however, highly expressed in sarcoma, CT antigens do not induce frequent humoral immune responses in sarcoma patients.
    [Show full text]
  • Open Data for Differential Network Analysis in Glioma
    International Journal of Molecular Sciences Article Open Data for Differential Network Analysis in Glioma , Claire Jean-Quartier * y , Fleur Jeanquartier y and Andreas Holzinger Holzinger Group HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 2/V, 8036 Graz, Austria; [email protected] (F.J.); [email protected] (A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 27 October 2019; Accepted: 3 January 2020; Published: 15 January 2020 Abstract: The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes.
    [Show full text]
  • WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T (51) International Patent Classification: David [US/US]; 13539 N . 95th Way, Scottsdale, AZ C12Q 1/68 (2006.01) 85260 (US). (21) International Application Number: (74) Agent: AKHAVAN, Ramin; Caris Science, Inc., 6655 N . PCT/US20 12/0425 19 Macarthur Blvd., Irving, TX 75039 (US). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 14 June 2012 (14.06.2012) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, English (25) Filing Language: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, Publication Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (30) Priority Data: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/497,895 16 June 201 1 (16.06.201 1) US MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 61/499,138 20 June 201 1 (20.06.201 1) US OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, 61/501,680 27 June 201 1 (27.06.201 1) u s SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 61/506,019 8 July 201 1(08.07.201 1) u s TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Usbiological Datasheet
    FCRL4, CT (FCRL4, FCRH4, IFGP2, IRTA1, Fc receptor- like protein 4, Fc receptor homolog 4, IFGP family protein 2, Immune receptor translocation-associated protein 1, CD307d) (FITC) Catalog number 035592-FITC Supplier United States Biological This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. Applications Suitable for use in Western Blot, FLISA and Flow Cytometry (Not Tested). Other applications have not been tested. Recommended Dilution Optimal dilutions to be determined by the researcher. Storage and Stability Store product at 4°C if to be used immediately within two weeks. For long-term storage, aliquot to avoid repeated freezing and thawing and store at -20°C. Aliquots are stable at -20°C for 12 months after receipt. Dilute required amount only prior to immediate use. Further dilutions can be made in assay buffer. Caution: FITC conjugates are sensitive to light. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Note Applications are based on unconjugated antibody. Immunogen KLH-conjugated synthetic peptide mapping to a fragment of residues within amino acids 480-507 in the C-terminal region of human FCRL4.
    [Show full text]
  • Pathway-Guided Analysis Identifies Myc-Dependent Alternative Pre-Mrna Splicing in Aggressive Prostate Cancers
    Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers John W. Phillipsa,1, Yang Panb,1, Brandon L. Tsaia, Zhijie Xiea, Levon Demirdjianc, Wen Xiaoa, Harry T. Yangb, Yida Zhangb, Chia Ho Lina, Donghui Chenga, Qiang Hud, Song Liud, Douglas L. Blacka, Owen N. Wittea,e,f,g,h,2, and Yi Xinga,b,c,i,2 aDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095; bBioinformatics Interdepartmental Graduate Program, University of California, Los Angeles, CA 90095; cCenter for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104; dDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263; eDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; fMolecular Biology Institute, University of California, Los Angeles, CA 90095; gJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095; hEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095; and iDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 Contributed by Owen N. Witte, January 2, 2020 (sent for review September 16, 2019; reviewed by Colin C. Collins and Han Liang) We sought to define the landscape of alternative pre-mRNA splicing treatment-related neuroendocrine prostate cancer (NEPC) has in prostate cancers and the relationship of exon choice to known been aided by large-scale genomic and transcriptomic studies of cancer driver alterations. To do so, we compiled a metadataset patient samples representing each form of the disease (10–13).
    [Show full text]