Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
Methods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2ober 2014Development of a Tissue Image Analysis Algorithm for Celiac Drug DevelopmentErik Hagendorn, Christa Whitney-Miller, Aaron Huber, and Steven J. PottsAbstractCeliac disease, an immune-mediated condition related to gluten sensitivity, is gaining pharmaceutical development interest. Recent conv Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2ersations with the US Food and Drug Administration (FDA) indicate pathology readouts from intestinal biopsies will continue to be a primary clinical tEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
rial endpoint. ‘Hie existing methodology, the Marsh-Oberhuber score, is a qualitative assessment of celiac severity, combining a morphological criteriMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2(IEL) counts. A stereology and image analysis based whole slide imaging methodology was developed for use in Cl.IA based clinical trials. Experimental Design: A series often normal and ten abnormal patient small bowel biopsies were manually evaluated by two pathologists to determine celiac disease ( Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2CD) state using the standard Marsh score. Two quantitative methods were developed an automated stercological methodology was used to evaluate surfaceEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
area on whole slide images and an image analysis complementary approach. Methods: Stcreology line probes were used to count one-dimensional “hits” on Methods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2hrough the epithelium of the reference tissue to background, or vice versa. Results: There was strong concordance between the pathologist scores, and the automated stercology analysis, with the automated approaches able to sufficiently delineate intermediate grades of disease, normally more difficul Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2t in visual assessments. Conclusion: rhe quantitative methodology is a valuable addition to Cl.IA based clinical trials. Quantita tion provides reprodEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
ucible and unbiased endpoints that can evaluate both the morphological and immune response in therapeutic clinical studies.Key words Celiac disease, TMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2harmaceutical drug development as well as a prime example of the difficulties ill quantifying morphology in clinical tissue biopsies. Approximately 1 % of the United States population has celiac disease, and in Western Europe the numbers range from 2.4 % in Finland to 0.3 % in Germany 111. Of the 1. Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 28 million Americans with celiac disease, 1.4 million of them arc not aware they have the digestive141142 Erik Hagendom et al.disorder 12 Ị. Partly thiEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
s low diagnosis rate is due to the complexity of symptoms. Celiac is an immune reaction to the gliadin in gluten, a complex glycoprotein rich in proliMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2alnutrition, anemia, and/or joint pain. Other presentations include constipation, depression, fatigue, osteoporosis, acid reflux, infcrtil ity, dermatological conditions, as well as others. The average time to diagnosis can be years, and many medical practitioners, particularly in the United States, Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2 remain highly ignorant of the complexity of potential symptoms. Patients arc generally diagnosed by meeting four of five rules: (1) typical clinicalEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
symptoms of celiac disease, (2) positive serological markers such as scrum anti transglutaminase (TIG) antibodies or anti gliadin antibodies, (3) smalMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2, and (5) improvement of symptoms on a gluten free diet [31.Despite the availability of serologic tests, the small intestinal biopsy remains the gold standard for diagnosis. I listology scoring is based on the Marsh Oberhuber classification, focused on increased intraepithelial lymphocytes (lELs), c Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2rypt hyperplasia, and villous atrophy (Table 1) 141.Until recently, celiac has received scant attention from the pharmaceutical industry, primarily beEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
cause of the perceived compc tition of an available low-cost cure, the strict lifelong adoption of a gluten-free diet. But compliance with this diet iMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2nsitivities to even trace levels of gluten is a substantial subset of celiacs who do not respond to a gluten-free diet, termed refractory celiac disease (RCD). It may be that the combination of RCD patients and patients with extremely high sensitivities to glutenTable 1 Marsh-Oberhuber classificatio Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2n of celiac diseaseMarsh classType of lesionVillous architectureCryptslELsMarsh IInfiltrativeNormalNormal>30/100 cntcrocytcsMarsh IIInfiltrative-hyperEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
plasticNormalHyperplasia>30/100 cntcrocytcsMarsh III3AFlat destructiveMild villous atrophyHyperplasia>30/100 cntcrocytcs3BFlat destructiveModerate vilMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2us atrophyHyperplasia>30/100 enterocytesDevelopment of a Tissue Image Analysis Algorithm for Celiac Drug Development 143 will be enough to demonstrate to pharmaceutical executives that a market docs indeed exist and demand is growing.Patients with celiac disease arc at risk for a number of long term Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2 complications, including osteoporosis, small intestinal lymphoma, type 1 diabetes, thyroid and liver disorders, psoriasis, and lupus 151. In childrenEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
, early detection and compliance with a gluten-free diet can lead to risk profiles equivalent to the general population; however, adults who were idenMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2 years, several celiac drug programs have emerged, primarily driven by small innovative firms. Alvinc Pharmaceuticals ALV003 recently published Phase 2 trials results with a glutcnasc that breaks dow n gluten and is designed to be part of a gluten-free diet for individuals with high gluten sensitivi Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2ty |6). Biopsies from subjects in the placebo group showed evidence of mucosal injury after gluten challenge, w ith a mean villous height to crypt depEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
th ratio changing from 2.8 before challenge to 2.0 afterward, and the density of CD3+ intraepithelial lymphocytes changing from 61 to 91 cclls/mm afteMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2 to measure the villous height to crypt depth ratio, given the variable geometries of the villi.InimunusanT is pursuing a vaccine with Ncxvax2 in Phase I, with the attempt to introduce immune tolerance to gluten in individuals with the DQ2 gene. Alba Therapeutics partnered with Shire Pharmaceuticals Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2 on AT 1001, a drug that attempts to close the tight junctions between cndocytcs, lowering leaky gut symp toms. In 2009, early phase I trials were unsEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
uccessful, and Ccphalon acquired rights to the compound in 2011, and recently initiated Phase 3 trials 171.BioLincRx’s BL-7010 binds directly to gluteMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2ne of the primary endpoints for clinical trials in celiac disease will be the biopsy 181. The Marsh-Oberhuber system was designed as a research tool for staging during diagnosis, not as a scoring scheme for response to therapy. Another difficulty is that the Marsh system includes both immunologic re Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2sponse (the presence ofTELs) as well as villous morphology (villi height to crypt depth ratio). While the manual measurement of villous height to crypEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
t depth ratio has been used in some clinical trials, the villi do not orient perfectly, making measurements difficult as a line needs to be drawn fromMethods in Pharmacology and Toxicology (2015): 141-152 DOI 10.1007/7653.2014_25©Springer Science+Bosiness Media New York 2014Published online: 25 Octo Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2luating morphological changes and immune response in biopsy samples. In this chapter we describe a144 Erik Hagendorn et al.novel approach to quantifying villous morphology using both image analysis and automated stcrcology techniques. These two approaches arc compared with manual pathology grading t Ebook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2o deter mine their suitability for use in pharmaceutical clinical trials.2 MethodologyH&E stained sections of 20 human duodenal biopsies were reviewedEbook Molecular histopathology and tissue biomarkers in drug and diagnostic development: Part 2
by two pathologists. Each section contained 1 6 tissue fragments. The pathologists were blinded to the reported diagnosis and any laboratory results.Gọi ngay
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