المؤلفون: Patel, Sandip P, Othus, Megan, Chae, Young Kwang, Giles, Francis J, Hansel, Donna E, Singh, Preet Paul, Fontaine, Annette, Shah, Manisha H, Kasi, Anup, Al Baghdadi, Tareq, Matrana, Marc, Gatalica, Zoran, Korn, W Michael, Hayward, Jourdain, McLeod, Christine, Chen, Helen X, Sharon, Elad, Mayerson, Edward, Ryan, Christopher W, Plets, Melissa, Blanke, Charles D, Kurzrock, Razelle

المصدر: Clinical Cancer Research. 26(10)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Cancer, Clinical Research, Orphan Drug, Health Disparities, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, CTLA-4 Antigen, Female, Follow-Up Studies, Humans, Ipilimumab, Male, Middle Aged, Neuroendocrine Tumors, Nivolumab, Prognosis, Programmed Cell Death 1 Receptor, Prospective Studies, Survival Rate, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis

الوصف: PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9dd0221wTest
https://escholarship.org/content/qt9dd0221w/qt9dd0221w.pdfTest

المؤلفون: Strosberg, Jonathan, Mizuno, Nobumasa, Doi, Toshihiko, Grande, Enrique, Delord, Jean-Pierre, Shapira-Frommer, Ronnie, Bergsland, Emily, Shah, Manisha, Fakih, Marwan, Takahashi, Shunji, Piha-Paul, Sarina A, O'Neil, Bert, Thomas, Sajeve, Lolkema, Martijn P, Chen, Menghui, Ibrahim, Nageatte, Norwood, Kevin, Hadoux, Julien

المصدر: Clinical Cancer Research. 26(9)

مصطلحات موضوعية: Digestive Diseases, Clinical Research, Cancer, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Programmed Cell Death 1 Receptor, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: PurposeKEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).Patients and methodsPembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary).ResultsA total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29-80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1-positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6-33.4). ORR was 3.7% (95% CI, 1.0-9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1-negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5-5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8-32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3-5 AEs.ConclusionsPembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/26j6b562Test

المؤلفون: Wolin, Edward, Mita, Alain, Mahipal, Amit, Meyer, Tim, Bendell, Johanna, Nemunaitis, John, Munster, Pam N, Paz-Ares, Luis, Filvaroff, Ellen H, Li, Shaoyi, Hege, Kristen, de Haan, Hans, Mita, Monica

المصدر: PloS one. 14(9)

مصطلحات موضوعية: Humans, Neuroendocrine Tumors, Carcinoid Tumor, Gastrointestinal Neoplasms, Pyrazines, Administration, Oral, Cohort Studies, Maximum Tolerated Dose, Adult, Aged, Middle Aged, Female, Male, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Administration, Oral, General Science & Technology

الوصف: Second-generation mammalian target of rapamycin (mTOR) inhibitors such as CC-223 may have theoretical advantages over first-generation drugs by inhibiting TOR kinase in mTOR complex 1 (mTORC1) and 2 (mTORC2), potentially improving clinical efficacy for well-differentiated neuroendocrine tumors (NET).Enrolled patients had metastatic, well-differentiated NET of non-pancreatic gastrointestinal or unknown origin, with/without carcinoid symptoms, had failed ≥1 systemic chemotherapy, and were taking a somatostatin analog (SSA). Oral once-daily CC-223 was administered in 28-day cycles starting at 45 mg (n = 24), with a subsequent cohort starting at 30 mg (n = 23). Objectives were to evaluate tolerability, preliminary efficacy, and pharmacokinetic and biomarker profiles of CC-223. Forty-seven patients completed the study, with mean treatment duration of 378 days and mean dose of 26 mg; 26% of patients remained on the starting dose. Most frequent grade ≥3 toxicities were diarrhea (38%), fatigue (21%), and stomatitis (11%). By investigator, 3 of 41 evaluable patients (7%) showed partial response (PR) and 34 (83%) had stable disease (SD) for a disease control rate (DCR) of 90% (95% confidence interval [CI] 76.9-97.3%). Duration of PR was 125-401 days; median SD duration was 297 days (min-max, 50-1519 days). Median progression-free survival was 19.5 months (95% CI 10.4-28.5 months). Carcinoid symptoms of flushing, diarrhea, or both improved in 50%, 41%, and 39% of affected patients, respectively. For the first time, this study describes that a second-generation mTOR pathway inhibitor can result in highly durable tumor regression and control of NET carcinoid symptoms. The manageable safety profile, high DCR, and durable response, coupled with reduction in carcinoid symptoms refractory to SSA, make CC-223 a promising agent for further development.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9c61n8fdTest

المؤلفون: Olaf M. Dekkers, Gerlof D. Valk, Wouter T Zandee, M. R. Vriens, Wouter W. de Herder, Bas Havekes, Mirthe J Klein Haneveld, Annenienke C van de Ven, Peter H. Bisschop, Carolina R.C. Pieterman, Madeleine L. Drent, Annemarie A Verrijn Stuart, Mark J C van Treijen, Rachel S van Leeuwaarde

المساهمون: Internal Medicine, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Endocrinologie (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Endocrinology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health

المصدر: Journal of Clinical Endocrinology and Metabolism, 106, 3515-3525
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. Endocrine Society
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. ENDOCRINE SOC
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. The Endocrine Society
Journal of Clinical Endocrinology & Metabolism, 106(12), 3515-3525. Oxford University Press
Journal of Clinical Endocrinology and Metabolism, 106, 12, pp. 3515-3525
Journal of clinical endocrinology and metabolism, 106(12), 3515-3525. The Endocrine Society
Klein Haneveld, M J, van Treijen, M J C, Pieterman, C R C, Dekkers, O M, van de Ven, A, de Herder, W W, Zandee, W T, Drent, M L, Bisschop, P H, Havekes, B, Vriens, M R, Verrijn Stuart, A A, Valk, G D & van Leeuwaarde, R S 2021, ' Initiating Pancreatic Neuroendocrine Tumor (pNET) Screening in Young MEN1 Patients : Results from the DutchMEN Study Group ', Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 12, pp. 3515-3525 . https://doi.org/10.1210/clinem/dgab569Test

مصطلحات موضوعية: Oncology, Male, Databases, Factual, Endocrinology, Diabetes and Metabolism, Neuroendocrine Tumors/diagnosis, Clinical Biochemistry, Disease, Biochemistry, multiple endocrine neoplasia type 1, Endocrinology, Medicine, Age of Onset, Multiple endocrine neoplasia, Child, Early Detection of Cancer, Netherlands, ENDOCRINE NEOPLASIA TYPE-1, education.field_of_study, INTERVAL-CENSORED-DATA, Middle Aged, Prognosis, Penetrance, age-related penetrance, Tumor Burden, Survival Rate, Neuroendocrine Tumors, Child, Preschool, Cohort, surveillance, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, Diagnostic Imaging, medicine.medical_specialty, pancreatic NET, Adolescent, Population, Context (language use), Netherlands/epidemiology, Databases, Young Adult, SDG 3 - Good Health and Well-being, Internal medicine, Humans, MEN1, Pancreatic Neoplasms/diagnosis, education, Preschool, Survival analysis, Factual, Aged, Retrospective Studies, business.industry, Biochemistry (medical), medicine.disease, Pancreatic Neoplasms, Multiple Endocrine Neoplasia Type 1/physiopathology, Early Detection of Cancer/methods, business, Follow-Up Studies

الوصف: ContextNonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate.ObjectiveThe aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.MethodsPancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.ResultsFive of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET–free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.ConclusionAnalyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2ce36b25c25d31e1a499d42dbc31157Test
https://doi.org/10.1210/clinem/dgab569Test

المؤلفون: Beek, D.J. van, Nell, S., Vorselaars, W.M.C.M., Bonsing, B.A., Eijck, C.H.J. van, Goor, H. van, Dijkum, E.N.J. van, Dejong, C.H.C., Valk, G.D., Rinkes, I.M.B., Vriens, M.R., DutchMEN Study Grp DMSG

المساهمون: RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Heelkunde (9), Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health

المصدر: Annals of Surgical Oncology, 28, 8, pp. 4387-4399
Annals of Surgical Oncology, 28, 4387-4399
Annals of Surgical Oncology, 28(8), 4387-4399. Springer, Cham
Annals of Surgical Oncology, 28(8), 4387-4399. Springer New York
Annals of surgical oncology, 28(8), 4387-4399. Springer New York
Annals of Surgical Oncology
Annals of Surgical Oncology, 28(8), 4387-4399. SPRINGER

مصطلحات موضوعية: Adult, medicine.medical_specialty, Chyle, surgical-management, Population, INTERNATIONAL STUDY-GROUP, 030209 endocrinology & metabolism, Neuroendocrine tumors, prognostic-factors, PANCREATIC SURGERY, CLASSIFICATION, Whipple Procedure, 03 medical and health sciences, Pancreatectomy, 0302 clinical medicine, Multiple Endocrine Neoplasia Type 1, Humans, Medicine, Endocrine Tumors, education, education.field_of_study, Gastric emptying, business.industry, Incidence (epidemiology), natural-history, medicine.disease, endocrine neoplasia type-1, Surgery, Pancreatic Neoplasms, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Neuroendocrine Tumors, DEFINITION, Oncology, 030220 oncology & carcinogenesis, LIMITED DISEASE, Cohort, PANCREATICODUODENECTOMY, business, Complication, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]

الوصف: Background Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore, the incidence and severity of complications after major surgery for MEN1-related dpNETs were assessed. Methods Patients were selected from the population-based Dutch MEN1 database if they had undergone a Whipple procedure or total pancreatectomy from 2003 to 2017. Complications were graded according to the Clavien–Dindo classification (grade III or higher complications were considered a severe complication) and definitions from the International Study Group of Pancreatic Surgery. The Cumulative Complication Index (CCI®) was calculated as the sum of all complications weighted for their severity. Univariable logistic regression was performed to assess potential associations between predictor candidates and a severe complication. Results Twenty-seven patients (median age 43 years) underwent a major duodenopancreatic resection, including 14 Whipple procedures and 13 total pancreatectomies. Morbidity and mortality were 100% (27/27) and 4% (1/27), respectively. A severe complication occurred in 17/27 (63%) patients. The median CCI® was 47.8 [range 8.7–100]. Grade B/C pancreatic fistulas, delayed gastric emptying, bile leakage, hemorrhage, and chyle leakage occurred in 7/14 (50%), 10/27 (37%), 1/27 (4%), 7/27 (26%), 3/27 (11%) patients, respectively. Patients with a severe complication had longer operative time and higher blood loss. After Whipple, new-onset endocrine and exocrine insufficiency occurred in 1/13 and 9/14 patients, respectively. Conclusions Major duodenopancreatic surgery in MEN1 is associated with a very high risk of severe complications and cumulative burden of complications and should therefore be reserved for a select subgroup of patients with MEN1-related dpNETs.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b6f21e53a7a2bed247f880c214f2b9eTest
https://cris.maastrichtuniversity.nl/en/publications/6492b2d1-8174-4316-a411-d8dd00f9cfa6Test

المؤلفون: Andrew Heryet, Newton A C S Wong, Josep Linares, Sophie Beavers, Pelvender S Gill

المصدر: Histopathology. 79:252-259

مصطلحات موضوعية: Adult, Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Endoscopic ultrasound, Pathology, medicine.medical_specialty, Histology, Adolescent, Duodenum, Calponin, Synaptophysin, Pathology and Forensic Medicine, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Biomarkers, Tumor, medicine, Humans, Inhibins, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Mucin-6, Pancreas, Aged, Glucose Transporter Type 1, medicine.diagnostic_test, biology, business.industry, Calcium-Binding Proteins, Cystadenoma, Serous, Microfilament Proteins, Stomach, General Medicine, Gold standard (test), Middle Aged, Serous Cystadenoma, Immunohistochemistry, digestive system diseases, Neuroendocrine Tumors, 030104 developmental biology, medicine.anatomical_structure, Fine-needle aspiration, 030220 oncology & carcinogenesis, biology.protein, Female, business

الوصف: AIMS Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET. METHODS AND RESULTS Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6. CONCLUSIONS Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::734457d2491a0b7c18bd9dfa483571dbTest
https://doi.org/10.1111/his.14362Test

المؤلفون: Haiying Xu, Anil Kotte, Marina Baretti, Robert A. Anders, Feriyl Bhaijee, Marianna Zahurak, Timothy M. Pawlik, Elizabeth L. Engle, Ana De Jesus-Acosta, Qingfeng Zhu

المصدر: Pancreas. 50:719-726

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, CD3 Complex, T-Lymphocytes, Endocrinology, Diabetes and Metabolism, Programmed Cell Death 1 Receptor, Neuroendocrine tumors, Gastroenterology, B7-H1 Antigen, Young Adult, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Endocrinology, Immune system, Internal medicine, PD-L1, Biomarkers, Tumor, Tumor Microenvironment, Internal Medicine, medicine, Humans, Aged, Gastrointestinal Neoplasms, Retrospective Studies, Tumor microenvironment, Hepatology, biology, Tumor-infiltrating lymphocytes, business.industry, Odds ratio, Middle Aged, medicine.disease, Progression-Free Survival, Pancreatic Neoplasms, Neuroendocrine Tumors, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, Female, 030211 gastroenterology & hepatology, Pancreas, business, CD8

الوصف: OBJECTIVES The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS). METHODS Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8429160a0cbd5f891c86624a537e751Test
https://doi.org/10.1097/mpa.0000000000001831Test

المؤلفون: Márton Doleschall, Anikó Somogyi, Magdolna Herold, Zoltán Herold, Attila Patócs, Peter Nagy

المصدر: Journal of Diabetes Investigation, Vol 11, Iss 4, Pp 865-873 (2020)
Journal of Diabetes Investigation

مصطلحات موضوعية: 0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Neuroendocrine tumors, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Prospective Studies, biology, C-Peptide, Glutamate Decarboxylase, Chromogranin A, Enterochromaffin‐like cell hyperplasia, General Medicine, Articles, Hyperplasia, Clinical Science and Care, Autoimmune gastritis, Gastritis, Disease Progression, Biomarker (medicine), Female, Original Article, Adult, medicine.medical_specialty, endocrine system, Enterochromaffin-like Cells, Autoimmune Gastritis, 030209 endocrinology & metabolism, Diseases of the endocrine glands. Clinical endocrinology, Autoimmune Diseases, 03 medical and health sciences, Islets of Langerhans, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Autoantibodies, Glycated Hemoglobin, Type 1 diabetes, Hungary, business.industry, medicine.disease, RC648-665, 030104 developmental biology, Diabetes Mellitus, Type 1, chemistry, biology.protein, Glycated hemoglobin, business

الوصف: Aims/Introduction The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin‐like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities. Materials and Methods A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy. Results Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P
A slight, but steady elevation in chromogranin A (CgA) level was observed to co‐vary with the duration of type 1 diabetes. Approximately 20% of the patients had elevated serum CgA levels, which was associated with higher glycated hemoglobin levels. Enterochromaffin‐like cell hyperplasia and autoimmune gastritis was significantly more frequent in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin‐like cell hyperplasia accompanied by CgA elevation. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::741a714d78d44aaf78f9e4604804fd0eTest
https://doaj.org/article/3dbcf3ebbb9e4c5da1e3b87698b4805eTest

المؤلفون: Lara Frommer, Antonia Ebert, Jochem König, Detlef Schuppan, George J. Kahaly

المصدر: The Journal of Clinical Endocrinology & Metabolism. 105:2606-2615

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Adolescent, Autoimmune Gastritis, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Autoimmunity, 030209 endocrinology & metabolism, Context (language use), Neuroendocrine tumors, Biochemistry, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Predictive Value of Tests, Internal medicine, Gastrins, medicine, Humans, Polyendocrinopathies, Autoimmune, Aged, Autoantibodies, Type 1 diabetes, biology, business.industry, Biochemistry (medical), Autoantibody, Chromogranin A, Autoimmune polyendocrinopathy, Middle Aged, medicine.disease, Healthy Volunteers, Neuroendocrine Tumors, Cross-Sectional Studies, Diabetes Mellitus, Type 1, 030104 developmental biology, ROC Curve, Gastritis, biology.protein, Biomarker (medicine), Female, business, Biomarkers

الوصف: Context The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. Objective To investigate CgA utility as a marker of endocrine autoimmunity. Methods CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. Results Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P Conclusion CgA qualifies as a novel biomarker for T1D, AP, and AG.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4476ecb7764b2bf2e01dbbe01209f0eTest
https://doi.org/10.1210/clinem/dgaa288Test

المؤلفون: Kinga Németh, Lilla Reiniger, Borbála Szabó, Hajnalka Rajnai, Henriett Butz, Lilla Krokker, Katalin Mészáros, Attila Patócs, Sándor Czirják, Ildikó Krencz, Nikolette Szücs, Katalin Karaszi

المصدر: The Journal of Clinical Endocrinology & Metabolism. 105:2015-2026

مصطلحات موضوعية: Adult, DNA (Cytosine-5-)-Methyltransferase 1, Male, medicine.medical_specialty, Adenoma, Proliferation index, Ubiquitin-Protein Ligases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Decitabine, Biochemistry, DNA methyltransferase, Dioxygenases, Epigenesis, Genetic, Young Adult, chemistry.chemical_compound, Endocrinology, Pituitary adenoma, Proto-Oncogene Proteins, Internal medicine, Biomarkers, Tumor, medicine, Humans, Pituitary Neoplasms, Aged, Cell Proliferation, Aged, 80 and over, Biochemistry (medical), Tet methylcytosine dioxygenase 1, DNA, Neoplasm, DNA Methylation, Middle Aged, Prognosis, medicine.disease, Demethylating agent, DNA-Binding Proteins, Neuroendocrine Tumors, chemistry, Case-Control Studies, 5-Methylcytosine, DNMT1, Cancer research, Female, Follow-Up Studies, medicine.drug

الوصف: Background Cytosine intermediaries 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), epigenetic hallmarks, have never been investigated in pituitary neuroendocrine tumors (PitNET). Objective To examine methylation-demethylation status of global deoxyribonucleic acid (DNA) in PitNET tissues and to assess its correlation with clinical and biological parameters. Materials and Methods Altogether, 57 PitNET and 25 corresponding plasma samples were collected. 5mC and 5hmC were investigated using liquid chromatography–tandem mass spectrometry. Expression of DNA methyltransferase 1 (DNMT1); tet methylcytosine dioxygenase 1 through 3 (TET1-3); and ubiquitin-like, containing PHD and RING finger domains 1 and 2 (UHRF1-2) were measured by reverse transcription–polymerase chain reaction. Levels of 5hmC and UHRF1-2 were explored by immunohistochemistry. Effect of demethylating agent decitabine was tested on pituitary cell lines. Results 5hmC/5mC ratio was higher in less differentiated PitNET samples. A negative correlation between Ki-67 proliferation index and 5hmC, 5hmC to 5mC ratio were revealed. Higher 5mC was observed in SF-1 + gonadotroph adenomas with a higher Ki-67 index. Expressions of TET2 and TET3 were significantly higher in adenomas with higher proliferation rate. UHRF1 showed gradually increased expression in higher proliferative adenoma samples, and a significant positive correlation was detected between UHRF2 expression and 5hmC level. Decitabine treatment significantly decreased 5mC and increased 5hmC levels in both cell lines, accompanied with decreased cell viability and proliferation. Conclusion The demethylation process negatively correlated with proliferation rate and the ratio of 5hmC to 5mC was higher in less differentiated adenomas. Therefore, epigenetic markers can be potential biomarkers for PitNET behavior. Altering the epigenome in adenoma cells by decitabine decreased proliferation, suggesting that this treatment might be a novel medical treatment for PitNET.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::192d75572724e066ef5fcd90b46c5c18Test
https://doi.org/10.1210/clinem/dgaa156Test