-
51
المؤلفون: Daniel Hussey, Sarah E. Coupland, Daniel Chin, Justin W. Adams, Paul G. McMenamin, Waafiqa Alam, Michelle R. Quayle
المصدر: Medical Teacher. 43:189-197
مصطلحات موضوعية: Models, Anatomic, Rapid prototyping, Medical education, business.industry, Reproduction, Reproduction (economics), education, 3D printing, Context (language use), General Medicine, Education, Printing, Three-Dimensional, Humans, sense organs, Tomography, X-Ray Computed, Psychology, business, Human Pathology
الوصف: The teaching of medical pathology has undergone significant change in the last 30-40 years, especially in the context of employing bottled specimens or 'pots' in classroom settings. The reduction in post-mortem based teaching in medical training programs has resulted in less focus being placed on the ability of students to describe the gross anatomical pathology of specimens. Financial considerations involved in employing staff to maintain bottled specimens, space constraints and concerns with health and safety of staff and student laboratories have meant that many institutions have decommissioned their pathology collections. This report details how full-colour surface scanning coupled with CT scanning and 3 D printing allows the digital archiving of gross pathological specimens and the production of reproductions or replicas of preserved human anatomical pathology specimens that obviates many of the above issues. With modern UV curable resin printing technology, it is possible to achieve photographic quality accurate replicas comparable to the original specimens in many aspects except haptic quality. Accurate 3 D reproductions of human pathology specimens offer many advantages over traditional bottled specimens including the capacity to generate multiple copies and their use in any educational setting giving access to a broader range of potential learners and users.
-
52
المؤلفون: Bertil E. Damato, Antonio Eleuteri, Azzam F. G. Taktak, Heinrich Heimann, Sarah E. Coupland
المصدر: Global Perspectives in Ocular Oncology ISBN: 9783031082498
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::bc9b9f04a8c99abe66fa9dfefdfb9b06
https://doi.org/10.1007/978-3-031-08250-4_22 -
53
المؤلفون: Ziyaad Sultan, Sarah E. Coupland, Muhammed Jawad, James Hsuan, Krishna Yamini, Austin G McCormick
المصدر: Orbit (Amsterdam, Netherlands).
مصطلحات موضوعية: Ophthalmology, medicine.medical_specialty, medicine.anatomical_structure, Orbital trauma, business.industry, Grease, food and beverages, Medicine, Oculoplastics, Radiology, business, Orbit (anatomy)
الوصف: Orbital trauma involving high-pressure grease guns is rare and can cause significant morbidity due to retained intraorbital grease. Grease can appear similar to intraorbital air on cross-sectional imaging, and clinicians should have a high index of suspicion for retained intraorbital grease and know how to recognise this. In this case, we will share the clinical and radiological findings as well as management of retained intraorbital grease.
-
54
المؤلفون: Jonel Steffen, Justine R. Smith, Sarah E. Coupland
المصدر: Ocular Immunology and Inflammation
مصطلحات موضوعية: Oncology, Antimetabolites, Antineoplastic, medicine.medical_specialty, Retinal Neoplasms, medicine.medical_treatment, HIV Infections, Diagnosis, Differential, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Intraocular Lymphoma, Vitrectomy, Cytology, Internal medicine, Epidemiology, medicine, Humans, Immunology and Allergy, External beam radiotherapy, Lymphoma, AIDS-Related, 030203 arthritis & rheumatology, Radiotherapy, business.industry, Primary central nervous system lymphoma, medicine.disease, Vitreous Body, Ophthalmology, Methotrexate, 030221 ophthalmology & optometry, Rituximab, Intraocular lymphoma, business, medicine.drug, Vitreoretinal lymphoma
الوصف: Purpose: To describe the epidemiology, clinical characteristics, diagnosis and treatment of human immunodeficiency virus (HIV)-related primary vitreoretinal lymphoma (PVRL).Methods: Narrative literature review.Results: HIV-related PVRL occurs in persons who are relatively young and generally have very low CD4+ T-cell counts. Vitritis with subretinal or sub-retinal pigment epithelial infiltrates is typical. Vitreous cytology remains the gold standard for diagnosis, supplemented by flow cytometry and genetic analyses of tumor cells, and measurement of aqueous or vitreous interleukin-10 levels. Concurrent brain involvement also may establish the diagnosis. Treatment includes antiretroviral therapy (ART), systemic chemotherapy (usually methotrexate-based) and local ocular treatment (intravitreal methotrexate, intravitreal rituximab, external beam radiotherapy). Systemic chemotherapy is of uncertain value for PVRL without other central nervous system involvement. Prognosis is poor, but has improved significantly compared to the pre-ART era.Conclusions: Ophthalmologists should consider the diagnosis of PVRL in HIV-positive individuals who present with intermediate or posterior uveitis.
وصف الملف: application/pdf
-
55
المؤلفون: Yamini Krishna, Sarah E. Coupland, Austin McCormick
المصدر: Diagnostic Histopathology. 26:188-191
مصطلحات موضوعية: 0301 basic medicine, Nasal cavity, Pathology, medicine.medical_specialty, Histology, Nuclear moulding, business.industry, medicine.medical_treatment, Multimodal therapy, medicine.disease, Small-cell carcinoma, Pathology and Forensic Medicine, Radiation therapy, 03 medical and health sciences, Sinonasal undifferentiated carcinoma, Skull, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine, Immunohistochemistry, business
الوصف: Primary sinonasal neuroendocrine carcinoma (SNEC) is a rare aggressive sinonasal malignancy which typically occurs in the ethmoidal or maxillary sinuses, with or without nasal cavity involvement, of middle-aged patients (median age 53 years), with a slight male preponderance. No risk factors have been identified. Most patients present at advanced stages due to the lack of significant symptoms.1,4,5,8 Advanced tumours may invade the skull, orbit or brain. Staging is of limited value in predicting prognosis and recent literature clearly highlights the importance of histological diagnosis, particularly differentiation grade, in determining the prognosis and predicting treatment response. Nomenclature has been ambiguous, but broadly SNECs can be classified as well-, moderately- or poorly differentiated. The latter group includes sinonasal undifferentiated carcinoma and sinonasal small cell carcinoma. On histological examination, well-to-moderately differentiated tumours show medium-sized cells with large nuclei containing stippled or ‘salt/pepper’ chromatin and scant cytoplasm. Nuclear moulding, increased mitoses and apoptotic bodies are commonly seen. Immunohistochemistry reveals expression of neuroendocrine markers.1,4–7 Poorly-differentiated tumours may lose expression of neuroendocrine markers and differentiation from other poorly differentiated malignancies can be extremely difficult.1,4–7 Due to the limited number of reported cases, there is no clear consensus on management, although oncologists now advocate multimodal therapy. Combined surgery and radiotherapy is thought to beneficial in moderately and poorly-differentiated subtypes.1,4–8 We describe a classical case of SNEC with secondary orbital involvement, with a review of the current literature.
-
56
المؤلفون: Judy M. Coulson, Sarah E. Coupland, Helen Kalirai, Joseph J. Sacco, Joseph R. Slupsky, Andrew D. Duckworth, Ricardo A. de Azevedo, Carlos R. Figueiredo
المصدر: The Journal of Pathology
مصطلحات موضوعية: Uveal Neoplasms, 0301 basic medicine, CD74, digital spatial profiling, T-Lymphocytes, medicine.medical_treatment, chemical and pharmacologic phenomena, CD38, immunotherapy resistance, Pathology and Forensic Medicine, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Immune system, Biomarkers, Tumor, Tumor Microenvironment, NanoString, medicine, Humans, Immunologic Factors, Mass cytometry, Melanoma, Original Paper, BAP1, business.industry, Tumor Suppressor Proteins, immune profile, Immunotherapy, medicine.disease, Original Papers, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Cancer research, CyTOF, uveal melanoma, business, Ubiquitin Thiolesterase, Immunosuppressive Agents, CD8
الوصف: Immunotherapy using immune checkpoint inhibitors (ICIs) induces durable responses in many metastatic cancers. Metastatic uveal melanoma (mUM), typically occurring in the liver, is one of the most refractory tumours to ICIs and has dismal outcomes. Monosomy 3 (M3), polysomy 8q, and BAP1 loss in primary uveal melanoma (pUM) are associated with poor prognoses. The presence of tumour‐infiltrating lymphocytes (TILs) within pUM and surrounding mUM – and some evidence of clinical responses to adoptive TIL transfer – strongly suggests that UMs are indeed immunogenic despite their low mutational burden. The mechanisms that suppress TILs in pUM and mUM are unknown. We show that BAP1 loss is correlated with upregulation of several genes associated with suppressive immune responses, some of which build an immune suppressive axis, including HLA‐DR, CD38, and CD74. Further, single‐cell analysis of pUM by mass cytometry confirmed the expression of these and other markers revealing important functions of infiltrating immune cells in UM, most being regulatory CD8+ T lymphocytes and tumour‐associated macrophages (TAMs). Transcriptomic analysis of hepatic mUM revealed similar immune profiles to pUM with BAP1 loss, including the expression of IDO1. At the protein level, we observed TAMs and TILs entrapped within peritumoural fibrotic areas surrounding mUM, with increased expression of IDO1, PD‐L1, and β‐catenin (CTNNB1), suggesting tumour‐driven immune exclusion and hence the immunotherapy resistance. These findings aid the understanding of how the immune response is organised in BAP1 − mUM, which will further enable functional validation of detected biomarkers and the development of focused immunotherapeutic approaches. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
وصف الملف: application/pdf
-
57
المؤلفون: Arwin Groenewoud, Jie Yin, Maria Chiara Gelmi, Samar Alsafadi, Fariba Nemati, Didier Decaudin, Sergio Roman-Roman, Helen Kalirai, Sarah E. Coupland, Aart G. Jochemsen, Martine J. Jager, Ewa Snaar-Jagalska
الوصف: Uveal melanoma (UM) is the most common intraocular melanoma, derived from transformed melanocytes of the uvea. Although treatment of primary UM is usually successful, there is a high risk (up to 50%) of liver metastasis with negligible long-term survival. There are currently no reproducible patient-derived animal models that faithfully recapitulate the latter stages of metastatic dissemination of UM, hindering the discovery of curative treatments. To overcome this problem and to accelerate the development of new metastatic UM treatments, we developed a patient-derived zebrafish xenograft (zf-PDX) model, using spheroid cultures generated from metastatic and primary UM tissues. Engrafted UM cells derived from these spheroid cultures give rise to metastatic lesions and recapitulate the molecular features of UMs and their potential drug sensitivity. Importantly, harnessing this versatile model, we reveal a high sensitivity of circulating UM cells to ferroptosis induction in vivo by Erastin and RSL3. Our findings are further corroborated by supportive analysis of patient data implicating ferroptosis as a new, and druggable, target for the treatment of metastatic UM patients, specifically in those with BAP1 loss in the tumor.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::6027dd4f0ca40a2b8cace4461e8506b4
https://doi.org/10.1101/2021.10.26.465874 -
58
المؤلفون: Stine Dahl Vest, Sarah E. Coupland, Bita Esmaeli, Paul T. Finger, Gerardo F. Graue, Hans E. Grossniklaus, Tine Gadegaard Hindso, Frederik Holm, Santosh G. Honavar, Jwu Jin Khong, Marina Knudsen Kirkegaard, Penelope A. McKelvie, Lauge Hjorth Mikkelsen, Kaustubh Mulay, Peter Kristian Rasmussen, Volkert Siersma, Lene Dissing Sjö, Matthew C. Sniegowski, Bradley A. Thuro, Geeta K. Vemuganti, Steffen Heegaard
المصدر: The British journal of ophthalmology.
مصطلحات موضوعية: Cellular and Molecular Neuroscience, Ophthalmology, Sensory Systems
الوصف: AimsTo examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes.MethodsClinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality.ResultsOAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location.ConclusionDisease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.
-
59
المؤلفون: Jack S Crabb, Bo Hu, Geeng-Fu Jang, Belinda Willard, Sarah E. Coupland, Helen Kalirai, Arun D. Singh, John W. Crabb
المصدر: Cancers
CANCERS
Volume 13
Issue 14
Cancers, Vol 13, Iss 3520, p 3520 (2021)مصطلحات موضوعية: 0301 basic medicine, quantitative proteomics, Cancer Research, Quantitative proteomics, Proteomics, Article, CDH1, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, metastasis, RC254-282, prediction modeling, biology, Melanoma, immune profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, bioinformatics, medicine.disease, Immune checkpoint, 030104 developmental biology, Oncology, iTRAQ, 030220 oncology & carcinogenesis, Proteome, biology.protein, Cancer research, uveal melanoma
الوصف: Simple Summary This study pursued the proteomic analysis of primary uveal melanoma (pUM) for insights into the mechanisms of metastasis and protein biomarkers. Liquid chromatography tandem mass spectrometry quantitative proteomic technology was used to analyze 53 metastasizing and 47 non-metastasizing pUM. The determined proteome of 3935 proteins was very similar between the metastasizing and non-metastasizing pUM, but included the identification of 402 differentially expressed (DE) proteins. Bioinformatic analyses suggest significant differences in the immune response between metastasizing and non-metastasizing pUM. Immune protein profiling results were consistent with transcriptomic studies, showing the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as potential targets for immune therapy checkpoint blockade. Prediction modeling of the proteomic data identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy. Abstract Uveal melanoma metastases are lethal and remain incurable. A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM proteins relative to the normal choroid excised from UM donor eyes. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM (n = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune proteins (n = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as possible candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for protein-based prognostic methods for detecting UM metastasis.
وصف الملف: application/pdf
-
60
المؤلفون: Sarah E. Coupland, Antonio Eleuteri, Helen Kalirai, Bertil Damato, Carl Groenewald, Heinrich Heimann, Rumana Hussain, Azzam Taktak
المصدر: CANCERS
Cancers
Volume 13
Issue 9
Cancers, Vol 13, Iss 2267, p 2267 (2021)مصطلحات موضوعية: Oncology, Cancer Research, Monosomy, medicine.medical_specialty, monosomy 3, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Retrospective analysis, RC254-282, business.industry, Absolute risk reduction, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, metastatic risk, medicine.disease, Ocular oncology, Lead time bias, 030220 oncology & carcinogenesis, Cohort, 030221 ophthalmology & optometry, uveal melanoma, business, Lower mortality
الوصف: Our aim was to determine whether size impacts on the difference in metastatic mortality of genetically high-risk (monosomy 3) uveal melanomas (UM). We undertook a retrospective analysis of data from a patient cohort with genetically characterized UM. All patients treated for UM in the Liverpool Ocular Oncology Centre between 2007 and 2014, who had a prognostic genetic tumor analysis. Patients were subdivided into those with small (≤2.5 mm thickness) and large (>
2.5 mm thickness) tumors. Survival analyses were performed using Gray rank statistics to calculate absolute probabilities of dying as a result of metastatic UM. The 5-year absolute risk of metastatic mortality of those with small monosomy 3 UM was significantly lower (23%) compared to the larger tumor group (50%) (p = 0.003). Small disomy 3 UM also had a lower absolute risk of metastatic mortality (0.8%) than large disomy 3 UM (6.4%) (p = 0.007). Hazard rates showed similar differences even with lead time bias correction estimates. We therefore conclude that earlier treatment of all small UM, particularly monosomy 3 UM, reduces the risk of metastatic disease and death. Our results would support molecular studies of even small UM, rather than ‘watch-and-wait strategies’.وصف الملف: application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b78c4089c331e8fca7e2f0d7146cdbe
PDF full text from Publisher 
Full Text via ClinicalKey