نتائج البحث

1

Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium

المؤلفون: Wilder Alberto Palomino A, Bruce A. Lessey, David P. Schammel, Jae Wook Jeong, Tae Hoon Kim, Tsutomu Sasaki, Steven L. Young, Jeffrey L Deaton

المصدر: J Clin Endocrinol Metab

مصطلحات موضوعية: Adult, Infertility, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Carbazoles, Endometriosis, Mice, Transgenic, Context (language use), Endometrium, Heterocyclic Compounds, 4 or More Rings, Biochemistry, Epigenesis, Genetic, Mice, Young Adult, Endocrinology, Sirtuin 1, Internal medicine, medicine, Animals, Humans, Embryo Implantation, Online Only Articles, Progesterone, Uterine Diseases, Clinical Research Article, business.industry, Biochemistry (medical), Decidualization, Middle Aged, medicine.disease, Pathophysiology, Menstruation, Disease Models, Animal, medicine.anatomical_structure, Estrogen, Case-Control Studies, Immunohistochemistry, Female, business, Infertility, Female, hormones, hormone substitutes, and hormone antagonists

الوصف: Context Progesterone resistance, a known pathologic condition associated with a reduced cellular response to progesterone and heightened estrogen responses, appears to have a normal physiologic role in mammalian reproduction. The molecular mechanism responsible for progesterone resistance in normal and abnormal endometrium remains unclear. Objective To examine the roles of sirtuin-1 (SIRT1) in normal endometrium as well as endometrium associated with infertility and endometriosis, as an epigenetic modulator associated with progesterone resistance. Methods SIRT1 expression was examined by Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry in mouse uterus and human endometrium. Mice with uterine specific Sirt1 overexpression were developed to examine SIRT1’s role in endometrial function and endometriosis development. EX-527, a SIRT1 inhibitor, and SRT1720, a SIRT1 agonist, were also used to evaluate SIRT1 effect on endometriosis. Results In normal healthy women, endometrial SIRT1 is expressed only during menses. SIRT1 was dramatically overexpressed in the endometrium from women with endometriosis in both the epithelium and stroma. In mice, SIRT1 is expressed at the time of implantation between day 4.5 and 5.5 of pregnancy. Overexpression of SIRT1 in the mouse uterus leads to subfertility due to implantation failure, decidualization defects and progesterone resistance. SIRT1 overexpression in endometriotic lesions promotes worsening endometriosis development. EX-527 significantly reduced the number of endometriotic lesions in the mouse endometriosis model. Conclusions SIRT1 expression and progesterone resistance appears to play roles in normal endometrial functions. Aberrant SIRT1 expression contributes to progesterone resistance and may participate in the pathophysiology of endometriosis. SIRT1 is a novel and targetable protein for the diagnosis as well as treatment of endometriosis and the associated infertility seen in this disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef5e53b19305211668b317bc0451056bTest
https://doi.org/10.1210/clinem/dgab753Test

2

Neuroendocrine Liver Metastasis—a Specific Set of Markers to Detect Primary Tumor Sites

المؤلفون: Oskar Koperek, Bruno Niederle, Reto Kaderli, Aurel Perren, Andreas Selberherr, Philipp Riss, Christian Scheuba

المصدر: Selberherr, Andreas; Koperek, Oskar; Riss, Philipp; Scheuba, Christian; Kaderli, Reto; Perren, Aurel; Niederle, Bruno (2019). Neuroendocrine Liver Metastasis-a Specific Set of Markers to Detect Primary Tumor Sites. Endocrine pathology, 30(1), pp. 31-34. Springer 10.1007/s12022-018-9558-z <http://dx.doi.org/10.1007/s12022-018-9558-zTest>

مصطلحات موضوعية: Adult, Male, Serotonin, Pathology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, LIM-Homeodomain Proteins, Thyroid Nuclear Factor 1, Thyroid Transcription Factor 1, 610 Medicine & health, 030209 endocrinology & metabolism, Pathology and Forensic Medicine, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Biopsy, Biomarkers, Tumor, medicine, Humans, CDX2 Transcription Factor, Enhancer, CDX2, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Liver Neoplasms, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, Primary tumor, Neuroendocrine Tumors, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 570 Life sciences, biology, Female, Pancreas, business, Transcription Factors

الوصف: The diagnosis of neuroendocrine neoplasia (NEN) is often made at an advanced stage of disease, including hepatic metastasis. At this point, the primary may still be unknown and sometimes cannot even be detected by functional imaging, especially in very small tumors of the pancreas (pan) and small intestinal (si) entities. The site of the primary may be based on biopsy specimens of the liver applying a specific set of markers. Specimens of liver metastases from 87 patients with NENs were studied. In retrospect, 50 patients had si and 37 pan NENs. Tissue samples were evaluated by immunohistochemistry. The markers applied were insulin gene enhancer protein Islet-1 (ISL-1), homeobox protein CDX-2 (CDX2), thyroid transcription factor 1 (TTF-1), and serotonin. Positive stains for CDX2 were documented in 43 (86%) and for serotonin in 45 (90%) of 50 siNENs. Three panNENs were positive for CDX2 and one for serotonin, respectively. ISL-1 was negative throughout in siNENs and also negative in 8 of 50 panNENs (21.6%). TTF-1 was negative in more than 90% of the specimens of either entity. Immunohistochemical markers in liver metastasis can lead the way to the site of the primary NEN. They should always be used in combined clusters.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b88677cf170cc1158cccf1fd70c1bcbTest
https://doi.org/10.1007/s12022-018-9558-zTest

3

Inhibin A as a tumor marker for primary bilateral macronodular adrenal hyperplasia

المؤلفون: Constantine A. Stratakis, Crystal Kamilaris, Fady Hannah-Shmouni, Annabel Berthon, Fabio R. Faucz, Naris Nilubol, Samira M. Sadowski, Martha Quezado, Rachel Wurth

المصدر: Endocrinology, Diabetes & Metabolism Case Reports, Vol 1, Iss 1, Pp 1-6 (2020)
Endocrinology, Diabetes & Metabolism Case Reports

مصطلحات موضوعية: Male, Inhibin, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Receptor expression, Cushing's syndrome, White, Gynaecomastia, April, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Cortisol, Cushing syndrome, 0302 clinical medicine, Diabetes mellitus type 2, Diabetes mellitus type 1, Novel Diagnostic Procedure, Asian - Korean, Hyperglycaemia, Adrenal, Adrenal cortex, Adrenalectomy, Macronodular hyperplasia, Immunohistochemistry, Black - African, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Glucocorticoid, hormones, hormone substitutes, and hormone antagonists, Endocrine gland, medicine.drug, Adult, CT scan, medicine.medical_specialty, endocrine system, Macronodular Adrenal Hyperplasia, Histopathology, 030209 endocrinology & metabolism, Urinary free cortisol, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, Genetics, Weight gain, Tumor marker, lcsh:RC648-665, Inhibin A, business.industry, Hypogonadism, 17-hydroxysteroids, Hypercortisolaemia, medicine.disease, United States, ACTH, Endocrinology, Telangiectasias, Amenorrhoea, business, Molecular genetic analysis

الوصف: Summary Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS). This condition is characterized by glucocorticoid and/or mineralocorticoid excess, and is commonly regulated by aberrant G-protein coupled receptor expression may be subclinical, allowing the disease to progress for years undetected. Inhibin A is a glycoprotein hormone and tumor marker produced by certain endocrine glands including the adrenal cortex, which has not been previously investigated as a potential tumor marker for PBMAH. In the present report, serum inhibin A levels were evaluated in three patients with PBMAH before and after adrenalectomy. In all cases, serum inhibin A was elevated preoperatively and subsequently fell within the normal range after adrenalectomy. Additionally, adrenal tissues stained positive for inhibin A. We conclude that serum inhibin A levels may be a potential tumor marker for PBMAH. Learning points: PBMAH is a rare cause of CS. PBMAH may have an insidious presentation, allowing the disease to progress for years prior to diagnosis. Inhibin A is a heterodimeric glycoprotein hormone expressed in the gonads and adrenal cortex. Inhibin A serum concentrations are elevated in some patients with PBMAH, suggesting the potential use of this hormone as a tumor marker. Further exploration of serum inhibin A concentration, as it relates to PBMAH disease progression, is warranted to determine if this hormone could serve as an early detection marker and/or predictor of successful surgical treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9108ee8206d3d4c3bf9ee445b165a132Test
https://edm.bioscientifica.com/view/journals/edm/2020Test/1/EDM20-0006.xml

4

Dysregulated Interleukin -33/ST2 Pathway Perpetuates Chronic Inflammation in Hashimoto’s Thyroiditis

المؤلفون: Xinhao Liu, Xuan Wang, Jin-an Zhang, Qiu Qin, Xiaoqing Shao, Jian Xu

المصدر: Endocrine, Metabolic & Immune Disorders - Drug Targets. 19:1012-1021

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Hashimoto Disease, Thyroiditis, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Western blot, Internal medicine, medicine, Humans, Immunology and Allergy, Inflammation, Autoimmune disease, medicine.diagnostic_test, business.industry, Thyroid, Middle Aged, Interleukin-33, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Interleukin 33, 030104 developmental biology, Endocrinology, Real-time polymerase chain reaction, medicine.anatomical_structure, Chronic Disease, Immunohistochemistry, Female, business, Biomarkers, Signal Transduction, 030215 immunology

الوصف: Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::770a8394f162bcb86d91d3fd5ed596ddTest
https://doi.org/10.2174/1871530319666190226164309Test

5

DNA repair proteins may differentiate papillary thyroid cancer from chronic lymphocytic thyroiditis and nodular colloidal goiter

المؤلفون: Sami Yilmaz, Nese Karadag, Ömercan Topaloğlu, Bahri Evren, Ayse Cikim Sertkaya, Faruk Kılınç

المصدر: Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)

مصطلحات موضوعية: Male, Pathology, Goiter, DNA Repair, endocrine system diseases, Pathogenesis, Papillary thyroid cancer, 0302 clinical medicine, Endocrinology, Medicine, Thyroid cancer, DNA Modification Methylases, Multidisciplinary, Thyroid, Middle Aged, Immunohistochemistry, medicine.anatomical_structure, MutS Homolog 2 Protein, Thyroid Cancer, Papillary, 030220 oncology & carcinogenesis, Thyroidectomy, 030211 gastroenterology & hepatology, Female, MutL Protein Homolog 1, Goiter, Nodular, Adult, medicine.medical_specialty, endocrine system, Science, Hashimoto Disease, Follicular cell, Article, Diagnosis, Differential, 03 medical and health sciences, Humans, Thyroid Neoplasms, Chronic thyroiditis, neoplasms, Aged, Retrospective Studies, business.industry, Tumor Suppressor Proteins, DNA, medicine.disease, Carcinoma, Papillary, digestive system diseases, DNA Repair Enzymes, MSH2, business, Lymphocytic Thyroiditis

الوصف: Malignant thyroid lesions are the most common malignancy of the endocrine glands with increasing rates in the last two decades. Papillary thyroid cancer is the most common thyroid malignancy. In our study, we aimed to quantitatively evaluate the levels of DNA repair proteins MSH2, MLH1, MGMT, which are representative blocks of patients diagnosed with papillary carcinoma, chronic thyroiditis, or colloidal goiter. Total or subtotal thyroidectomy material of 90 patients diagnosed with papillary carcinoma, nodular colloidal goiter, or chronic thyroiditis between 2009 and 2012 were retrospectively evaluated. Tissue samples obtained from paraffin blocks were stained with MGMT, MSH2, MLH1 proteins and their immunohistochemistry was evaluated. Prepared sections were examined qualitatively by an impartial pathologist and a clinician, taking into account the staining method under the trinocular light microscope. Although there was no statistically significant difference in MGMT, MSH2, MLH1, follicular cell positivity, staining intensity, and immunoreactivity values, papillary carcinoma cases showed a higher rate of follicular cell positivity, and this difference was more pronounced between papillary carcinoma and colloidal goiter. In the MSH2 follicular cell positivity evaluation, the difference between chronic thyroiditis and colloidal goiter was significant (p = 0.023). The difference between chronic thyroiditis and colloidal goiter was significant in the MSH2 staining intensity evaluation (p = 0.001). The difference between chronic thyroiditis and colloidal goiter was significant in MLH1 immunoreactivity evaluation (p = 0.012). Papillary carcinoma cases were demonstrated by nuclear staining only for MSH2 and MLH1 proteins as opposed to hyperplastic nodules. The higher levels of expression of DNA repair genes in malignant tumors compared to benign tumors are attributed to the functional activation of DNA repair genes. Further studies are needed for DNA repair proteins to be a potential test in the development and progression of thyroid cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b09a339ef660503d18023c0f7696dfeaTest
http://europepmc.org/articles/PMC8113225Test

6

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals

المؤلفون: Louise S. Dalbøge, Jens J. Holst, Hazem Hassan, Brynjulf Mortensen, Jakob Hendel, Steen Seier Poulsen, Jens Pedersen, Tina Jorsal, Tina Vilsbøll, Nicolai Rhee, Filip K. Knop, Jacob Jelsing, Sara L. Jepsen, Camilla D. Wahlgren, Peter Vilmann

المصدر: Diabetologia. 61:284-294

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Enteroendocrine Cells, Endocrinology, Diabetes and Metabolism, Prohormone convertase, 030209 endocrinology & metabolism, Enteroendocrine cell, Gastric Inhibitory Polypeptide, Biology, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Humans, Glucose homeostasis, Peptide YY, Large intestine, Enterochromaffin-like cell, Aged, Middle Aged, Immunohistochemistry, Glucagon-like peptide-1, Small intestine, Gastrointestinal Tract, Cross-Sectional Studies, Proprotein Convertase 2, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 2, Proprotein Convertase 1, Chromogranin A, Female, Proprotein Convertases

الوصف: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. NCT03044860.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::400d54ba24b9108ca2aa3b8f9c587a51Test
https://doi.org/10.1007/s00125-017-4450-9Test

7

Hypoxia and collagen crosslinking in the healthy and affected sites of periodontitis patients

المؤلفون: Gozde Isiker Kara, Ozkan Karatas, Fikret Gevrek, Fatma Uçan Yarkaç, Mehmet Murat Taskan, Hatice Balci Yuce

المصدر: Acta Odontologica Scandinavica. 77:600-607

الوصف: Present study suggests that diseased sites of periodontitis with stage 3 grade B and C had decreased fibroblast cell density, hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) expressions while increased inflammatory cell counts compared to both healthy sites of the periodontitis patients and healthy controls. Collagen maturation enzymes also decreased in the diseased sites. Objective: The present study aimed at determining markers of hypoxia and collagen crosslinking in healthy and diseased gingiva from healthy individuals and periodontitis patients. Methods: Group-1; healthy individuals, Group-2; healthy sites of periodontitis patients-stage 3 grade B, (H-GradeB) Group-3; diseased sites of periodontitis patients-stage 3 grade B, (D-GradeB). Group-4; healthy sites of periodontitis patients-stage 3 grade C, (H-GradeC). Group-5; diseased sites of periodontitis patients-stage 3 grade C, (D-GradeC). Plaque index (PI), gingival index (GI) and clinical attachment levels (CALs) were recorded. Gingival biopsies were obtained. Fibroblast and inflammatory cells were counted. HIF-1α, prolyl hydroxylase (PH), VEGF, lysyl oxidase (LOX) and lysyl hydroxylase (LH) levels were determined via immunohistochemistry. Results: Fibroblast cell counts were lower in D-GradeC and D-GradeB than other groups. C group had highest fibroblast cell counts. Inflammatory cell counts were highest in the D-GradeC and lowest in C group. HIF-1α levels were highest in C group and decreased in diseased sites. Lowest value was observed in D-GradeC group. VEGF, PH, and LH levels were higher in the control group compared to other groups. LOX levels were similar in the groups except for D-GradeC. LOX levels were similar in the groups except for D-GradeC which is significantly lower than those of the control group and healthy sites. Conclusions: The results revealed that diseased sites of periodontitis patients had decreased fibroblast cells, HIF and VEGF expressions while increased inflammatory cells. Collagen crosslinking tend to decrease with disease regardless of stage and grade of disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0f4a6b7e9771b0d840a051bde0beba6Test
https://doi.org/10.1080/00016357.2019.1624819Test

8

Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia

المؤلفون: C. Benedikt Westphalen, Annelore Altendorf-Hofmann, Katharina Brüwer, Jens Werner, Thomas Kirchner, Stefan Boeck, Volker Heinemann, Florian Bösch, Gabriele Schubert-Fritschle, Christoph J. Auernhammer, Martin K. Angele, Christine Spitzweg, Thomas Knösel

المصدر: Endocrine-Related Cancer. 26:293-301

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Programmed Cell Death 1 Receptor, B7-H1 Antigen, Young Adult, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Endocrinology, Cancer immunotherapy, Stomach Neoplasms, Internal medicine, Intestinal Neoplasms, Biomarkers, Tumor, medicine, Humans, Receptor, Grading (tumors), Aged, Aged, 80 and over, business.industry, Immunotherapy, Middle Aged, Survival Analysis, Immune checkpoint, Small intestine, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Neuroendocrine Tumors, Observational Studies as Topic, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, Neoplasm Grading, business, Pancreas

الوصف: Cancer immunotherapy has evolved major breakthroughs in the last years. The cell-surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), have been detected in various cancer types. However, the analysis on gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor-infiltrating lymphocytes (TILs). On protein level, we examined TILs, PD-1 and PD-L1 expression in tumor tissue of 244 GEP-NENs using immunohistochemistry. Expression levels were correlated with clinicopathological parameters including long-term survival in an observational study. In total, 244 patients could be included. Most of the patients had a NEN of the small intestine (52.5%) or the pancreas (29.5%). All tumors could be graded by their morphology and Ki67 index, with 57.8% G1, 34% G2 and 8.2% G3 tumors. High TILs (19.6%) and high PD-1 (16.1%) expression showed a significant correlation with shorter patient survival (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8e6d99bda04b43056b2a385562ce650Test
https://doi.org/10.1530/erc-18-0494Test

9

Evaluation of expression of somatostatin receptor 1, 2, 3, 5 and dopamine D2 receptor in spindle cell oncocytomas of posterior pituitary

المؤلفون: Martin Syrucek, Veronika Skarkova, Boris Rychly, Petra Kašparová, Jiri Soukup, Filip Gabalec, Ales Kohout

المصدر: Pituitary. 22:70-78

الوصف: Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs. We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST1, SST2, SST3, SST5 and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST1−5 and D2DR was further evaluated by western blot. Mean patient age was 61.8 years (range 47–71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST1 was noted in 1/5 cases, SST2 in 2/5 cases, including recurrent case but not the original case. SST3 was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST2, SST3 and D2DR expression was identified in all the samples, including two cases originally negative for SST2 and one case negative for SST3 by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST5 was observed. In the patient with the recurrent tumor, intensity of SST2, SST3 and D2DR expression varied between original tumor and its recurrence. We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST2 and SST3, while no expression of SST5 was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8a3617bb3187dcff8c392e13f4d0cefTest
https://doi.org/10.1007/s11102-018-00935-7Test

10

Analysis of the immune landscape of small bowel neuroendocrine tumors

المؤلفون: J. Strosberg, S Al Diffalha, Domenico Coppola, Mauro Cives

المصدر: Endocr Relat Cancer

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Carcinoid tumors, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Ileum, Neuroendocrine tumors, Gastroenterology, B7-H1 Antigen, Article, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Endocrinology, Immune system, Internal medicine, PD-L1, Intestinal Neoplasms, Immune Tolerance, medicine, Humans, Aged, Neoplasm Staging, Aged, 80 and over, biology, business.industry, Immunotherapy, Middle Aged, medicine.disease, Neuroendocrine Tumors, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Duodenum, biology.protein, Immunohistochemistry, Female, business

الوصف: Immune checkpoint inhibitors have shown promising results in different cancers, and correlation between immune infiltration, expression of programmed death-ligand 1 (PD-L1) by tumor cells and response to immunotherapy has been reported. There is limited knowledge regarding the immune microenvironment of small bowel (SB) neuroendocrine tumors (NETs). This work was aimed at characterizing the immune landscape of SB NETs. Expression of PD-L1 and programmed death-1 (PD-1) was evaluated by immunohistochemistry in 102 surgically resected, primary NETs of the duodenum, jejunum and ileum. Extent and characteristics of the tumor-associated immune infiltrate were also assessed and investigated in their prognostic potential. We detected the expression of PD-L1 in ≥1 and ≥50% of tumor cells in 40/102 (39%; 95% CI, 30–49%) and 14/102 (14%; 95% CI, 8–22%) cases respectively. Intratumor host immune response was apparently absent in 35/102 cases (34%; 95% CI, 25–44%), mild to moderate in 46/102 samples (45%, 95% CI, 35–55%), intense in 21/102 tumors (21%, 95% CI, 13–30%). Expression of PD-L1 and extent of immune infiltration were significantly higher in duodenal NETs as compared with jejunal/ileal NETs. A marked peritumoral host response was organized as ectopic lymph node-like structures in 18/102 cases (18%; 95% CI, 11–26%). Neither PD-L1 expression nor the degree of immune infiltration showed any prognostic significance. Overall, the immune landscape of SB NETs is heterogeneous, with adaptive immune resistance mechanisms prevailing in duodenal NETs. Clinical trials of immune checkpoint inhibitors should take into account the immune heterogeneity of SB NETs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7438c4a396980557e69a108693923bf2Test
https://doi.org/10.1530/erc-18-0189Test

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