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Sample records for neuroendocrine gh4c1 cells

  1. Foetal Leydig cells and the neuroendocrine system.

    Science.gov (United States)

    Sklebar, Duska; Semanjski, Kristina; Kos, Marina; Sklebar, Ivan; Jezek, Davor

    2008-01-01

    It has been shown that adult human Leydig cells express a number of neuroendocrine markers, and, therefore, could be considered as a part of the neuroendocrine system in the adult. A limited number of studies have dealt with the dynamics of development of human foetal Leydig cells, whereas studies on their neuroendocrine nature are still extremely rare. Therefore, the aim of our study was to investigate the development of human foetal Leydig cells in different weeks of gestation (wg) and to check if these cells express certain markers characteristic of the diffuse neuroendocrine system (DNS). Qualitative, quantitative histological studies and immunohistochemical analyses of human foetal testicular tissue have been performed. According to our data, Leydig cells formed a dynamic population of cells within the interstitum of testes in the period between 15 and 36 wg. The total number of Leydig cells of human foetal testes changed through different stages of gestation by means of 'pulsatile' dynamics (most likely, by following the variable level of gonadotropins). At early stages of development (15-17 wg) immunohistochemical reactions for the expression of neuron specific enolase (NSE) were positive within sex cords and between them, in the interstitum. Pro-spermatogonia in the sex cords were positive, as well as elongated spindle-shaped cells of the interstitum (very likely, precursors of Leydig cells). During the later stages of development (28-36 wg), excluding the pro-spermatogonia, the interstitial Leydig cells were also positive. The results of the immunohistochemical analyses (the expression of NSE) confirmed the hypothesis that human foetal Leydig cells were of neuroendocrine nature.

  2. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  3. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  4. Neuroendocrine small cell carcinoma of the uterine cervix.

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    Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

    2010-07-01

    Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

  5. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  6. Neurophysiology of magnocellular neuroendocrine cells: recent advances.

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    Hatton, G I; Li, Z H

    1998-01-01

    Magnocellular neuroendocrine cells of the hypothalamic paraventricular and supraoptic nuclei are responsible for most of the vasopressin and oxytocin in the peripheral blood as well as for central release of these peptides in selected brain areas. As the principal component of the hypothalamo-neurohypophysial system, these neurons have been a subject of continual study for half a century. The wealth of solid information from decades of in vivo studies has provided a firm basis for in vitro, brain slice and explant investigations of neural mechanisms involved in the control and regulation of vasopressin and oxytocin neurons. In vitro methods have revealed the presence and permitted the study of monosynaptic projections to supraoptic neurons from the olfactory bulbs, the tuberomammillary nuclei of the posterior hypothalamus and from the organum vasculosum of the lamina terminalis. Such methods have also facilitated the elucidation of the various ionic currents controlling neurosecretory cell activity as well as the roles of calcium binding proteins and release of calcium from internal stores. This review summarizes recent advances in our understanding of the afferent inputs that impinge upon these two cell types, and the cellular and molecular mechanisms intrinsic to these neurons that determine their activity patterns and, in part, their responses to incoming stimuli.

  7. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

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    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  8. Menadione inhibits MIBG uptake in two neuroendocrine cell lines

    NARCIS (Netherlands)

    Cornelissen, J.; Tytgat, G. A.; van den Brug, M.; van Kuilenburg, A. B.; Voûte, P. A.; van Gennip, A. H.

    1997-01-01

    In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line.

  9. Novel Treatment of Small-Cell Neuroendocrine of the Vagina

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    Kathryn Kostamo

    2018-01-01

    Full Text Available Background. Primary vaginal small-cell neuroendocrine carcinoma is an extremely rare and highly aggressive malignancy. Eighty-five percent of patients die within one year of diagnosis from metastatic disease despite multimodal therapy. Gene expression profiling of tumor tissue may be useful for treatment options for various malignancies. Case. A 34-year-old nulliparous woman was diagnosed with primary vaginal small-cell neuroendocrine carcinoma. Twenty weeks after the initial visit, she was diagnosed with recurrence and started on chemoradiation based on the results of gene expression profile of tumor tissue. She died 34 months after the initial visit and had a 14-month progression-free survival (PFS. Conclusion. Gene expression profile of tumor tissue in the management of primary vaginal small-cell neuroendocrine carcinoma may be helpful in extending progression-free survival.

  10. Large Cell Neuroendocrine Cancer (LCNEC of uterine cervix

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    Gehanath Baral

    2009-01-01

    Full Text Available A rare type of cervical cancer was encountered as a neuroendocrine cancer of cervix. Clinically, the patient presented with bleeding per vagina. She refused biopsy in her first visit and did not come for follow up. However, after few months she came and since there was a polypoid growth from cervix, she was advised to undergo hysterectomy. Histopathologically, it was diagnosed as large cell type of neuroendocrine cancer. Multimodality systemic treatment was offered as per literature. Ibrahim Med. Coll. J. 2009; 3(1: 36-38

  11. Interplay of CREB and ATF2 in Ionizing Radiation-Induced Neuroendocrine Differentiation of Prostate Cancer Cells

    Science.gov (United States)

    2011-06-01

    cancer cells to transdifferentiate into neuroendocrine-like (NE-like) cells, a process also known as neuroendocrine differentiation (NED) that is associated with disease progression and...by which prostate cancer cells survive the treatment and contribute to

  12. Prostatic neuroendocrine cells have a unique keratin expression pattern and do not express Bcl-2: cell kinetic features of neuroendocrine cells in the human prostate

    NARCIS (Netherlands)

    Xue, Y.; Verhofstad, A.; Lange, W.; Smedts, F.; Debruyne, F.; de la Rosette, J.; Schalken, J.

    1997-01-01

    We investigated the keratin phenotype and bcl-2 immunoreactivity of neuroendocrine cells in the human prostate to determine whether the postmitotic status of these cells is associated with protection from apoptosis by bcl-2 protein expression and to elucidate the possible cell kinetic relationship

  13. FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate.

    Science.gov (United States)

    Park, Jung Wook; Lee, John K; Witte, Owen N; Huang, Jiaoti

    2017-09-01

    The median survival of patients with small cell neuroendocrine carcinoma is significantly shorter than that of patients with classic acinar-type adenocarcinoma. Small cell neuroendocrine carcinoma is traditionally diagnosed based on histologic features because expression of current immunohistochemical markers is inconsistent. This is a challenging diagnosis even for expert pathologists and particularly so for pathologists who do not specialize in prostate cancer. New biomarkers to aid in the diagnosis of small cell neuroendocrine carcinoma are therefore urgently needed. We discovered that FOXA2, a pioneer transcription factor, is frequently and specifically expressed in small cell neuroendocrine carcinoma compared with prostate adenocarcinoma from published mRNA-sequencing data of a wide range of human prostate cancers. We verified the expression of FOXA2 in human prostate cancer cell lines and xenografts, patient biopsy specimens, tissue microarrays of prostate cancers with lymph node metastasis, primary small cell neuroendocrine carcinoma, and metastatic treatment-related small cell neuroendocrine carcinoma and cases from a rapid autopsy program. FOXA2 expression was present in NCI-H660 and PC3 neuroendocrine cell lines, but not in LNCAP and CWR22 adenocarcinoma cell lines. Of the human prostate cancer specimens, 20 of 235 specimens (8.5%) showed diagnostic histologic features of small cell neuroendocrine carcinoma as judged histologically. Fifteen of 20 small cell neuroendocrine carcinoma tissues (75%) showed strong expression of FOXA2 (staining intensity 2 or 3). FOXA2 expression was also detected in 9 of 215 prostate cancer tissues (4.2%) that were histologically defined as adenocarcinoma. Our findings demonstrate that FOXA2 is a sensitive and specific molecular marker that may be extremely valuable in the pathologic diagnosis of small cell neuroendocrine carcinoma.

  14. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  15. Metabolic PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter

    2008-01-01

    Neuroendocrine tumors originate from the diffuse neuroendocrine system. Embryologically the diffuse neuroendocrine system is derived from the neuoectoderm and the endoderm (gut). The function of diffuse neuroendocrine system cells is to regulate neighbouring cells (paracrine regulation) by the

  16. Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

    International Nuclear Information System (INIS)

    Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

    2005-01-01

    This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

  17. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

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    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  18. Large-Cell Neuroendocrine Carcinoma of the Esophagus: A Case from Saudi Arabia

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    Hadi Kuriry

    2015-10-01

    Full Text Available Neuroendocrine carcinomas of the esophagus are very rare, and the majority are high grade (poorly differentiated. They occur most frequently in males in their sixth and seventh decades of life. There have been no concrete data published on clinical features or on prognosis. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 66-year-old Saudi female with progressive dysphagia and weight loss. Upper endoscopy revealed an esophageal ulcerated mass.

  19. Combinatorial code of growth factors and neuropeptides define neuroendocrine differentiation in PC12 cells.

    NARCIS (Netherlands)

    Beaujean, D.; Rosenbaum, C.; Muller, H.W.; Willemsen, J.J.; Lenders, J.W.M.; Bornstein, S.R.

    2003-01-01

    Adrenal chromaffin cells constitute one of the first cell types to have been defined as a neuroendocrine cell type. Since they produce dopamine, these cells have been proposed for the treatment of neuronal deficits in human Parkinson's disease. However, the factors involved in the development of

  20. [Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

    Science.gov (United States)

    Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

    2006-09-01

    The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

  1. Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc

    NARCIS (Netherlands)

    Janse, C.

    2004-01-01

    During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during

  2. Gastric Collision Tumor Consisting of Mucinous Carcinoma and Large Cell Neuroendocrine Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Su Min; Lee, Ye Ri; Han, Eun Mee; Yeon, Jae Woo; Yoo, Jin Young; Choi, Jong Mun; Sim, Ji Ye [Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2010-06-15

    The concurrence of two different pathological tumors of the stomach is infrequent. Even rarer is a gastric collision tumor of both tumor types. Although there have been a few reported cases of gastric collision tumors that consisted of an adenocarcinoma and neuroendocrine carcinoma, to the best of our knowledge, there is no documented case report of a gastric collision tumor consisting of a mucinous carcinoma and large cell neuroendocrine carcinoma. We report a case of gastric collision tumor, consisting of a mucinous carcinoma and large cell neuroendocrine carcinoma that presented as abdominal discomfort in a 64-year-old man. This finding draws attention to the related findings from previous studies on gastric collision tumors

  3. [Neuroendocrine tumors of digestive system: morphologic spectrum and cell proliferation (Ki67 index)].

    Science.gov (United States)

    Delektorskaia, V V; Kushliskiĭ, N E

    2013-01-01

    This review deals with the analysis of up-to-date concepts ofdiferent types of human neuroendocrine tumors of the digestive system. It summarizes the information on the specifics of recent histological classifications and criteria of morphological diagnosis accounting histological, ultrastructural and immunohistochemical parameters. Current issues of the nomenclature as well as various systems of grading and staging are discussed. In the light of these criteria the results of the own research clinical value of the determination of cell proliferation in primary and metastatic gastroenteropancreatic neuroendocrine neoplasms on the basis of evaluation of the Ki67 antigen expression are also presented.

  4. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

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    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  5. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

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    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  6. Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature

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    Spinelli C

    2013-09-01

    Full Text Available Primary neuroendocrine carcinomas of the breast are extremely rare. Neuroendocrine tumors mainly occur in the broncopolmonary system and gastrointestinal tract. The diagnosis of small cell neuroendocrine carcinoma (SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. We are going to describe two cases and to discuss their clinical, radiological and pathological manifestations. Introduction: Neuroendocrine tumors are rare and slow-growing neoplasias derived from neuroendocrine cells. We describe two cases of small cell neuroendocrine carcinoma of the breast and discuss their clinical, radiological and pathological manifestations. Case report: Our patients are two Italian females (38 and 36 year-old with no family history of breast disease. In both cases the diagnosis was confirmed after surgery, when immunohistochemistry revealed a neuroendocrine differentiation of the tumor. The patients are alive and disease free after more than ten years of follow-up. Conclusion: Primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. After surgery, a strict follow-up including octreotide scan should be performed and this doesn’t differ from the one of the usual breast carcinoma.

  7. Chromophobe renal cell carcinoma of the kidney with neuroendocrine differentiation: A case report with review of literature

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    Ghadeer A Mokhtar

    2015-01-01

    Full Text Available Chromophobe renal cell carcinoma (chRCC is a distinctive type of malignant kidney tumor characterized by large cells with defined cell membrane. Primary renal neuroendocrine tumors (NET are rare with morphology similar to NET at other sites. There are few case reports describing the coexistence of these 2 neoplasms within the same tumor mass. We describe a case of chRCC with neuroendocrine features in a 70-year-old male patient who presented with hematuria and right flank pain. The histological and immunohistochemical features of both components were characteristic with no overlapping features. The neuroendocrine element was associated with nodal metastasis.

  8. Stress, the neuroendocrine system and mast cells: current understanding of their role in psoriasis.

    Science.gov (United States)

    Harvima, Ilkka T; Nilsson, Gunnar

    2012-03-01

    Psychological stress can activate the hypothalamic-pituitary-adrenal axis and sensory nerves in the brain and skin, resulting in the release of neuroendocrine and neural mediators such as, corticotropin-releasing hormone, neuropeptides, neurotrophins and α-melanocyte-stimulating hormone. These factors can activate mast cells to release proinflammatory mediators and some of them, for example, histamine, tryptase and nerve growth factor, can stimulate sensory C-fibers. Since corticotropin-releasing hormone, sensory nerves and mast cell numbers are increased in the psoriatic lesion, a feedforward loop can exist potentiating the inflammation. Studies in rats and mice have shown that mast cells are activated during standardized stress through corticotropin-releasing hormone and sensory nerves. Therefore, the role of stress, the neuroendocrine system and mast cells in psoriasis is discussed in this article.

  9. Christia vespertilionis plant extracts as novel antiproliferative agent against human neuroendocrine tumor cells.

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    Hofer, Daniela; Schwach, Gert; Ghaffari Tabrizi-Wizsy, Nassim; Sadjak, Anton; Sturm, Sonja; Stuppner, Hermann; Pfragner, Roswitha

    2013-06-01

    Neuroendocrine tumors respond poorly to radiation and conventional chemotherapy, hence surgical removal of the neoplastic tissue is still the most effective way of treatment. In an attempt to find new therapeutic plant extracts of Christia vespertilionis (CV) their antitumor potential in human medullary thyroid carcinoma (MTC) and human small intestinal neuroendocrine tumor (SI-NET) cell lines were tested. Proliferation and viability were analyzed using cell counting and WST-1 assay. Apoptosis was determined by microscopy, luminescence assays for caspases 3/7, and expression studies of apoptosis-related genes. CV extracts showed antiproliferative and proapoptotic effects in all MTC and SI-NET cell lines, whereby high growth inhibition was observed by treatment with the ethylacetate-extracts (CV-45) in tumor cell lines but not in normal human fibroblasts. Furthermore CV-45 treatment resulted in alterations of gene expression of PDCD5, MTDH and TNFRSF10b in MTC as well as in SI-NET cells. The results indicate that Christia vespertilionis could serve as an anticancer therapeutic for treatment of neuroendocrine tumors.

  10. Primary small cell neuroendocrine carcinoma of the breast: The histogenetic diatribe

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    Cabibi D

    2013-12-01

    Full Text Available The article entitled “Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature” by Spinelli et al. [1]. The authors stated that “the histogenesis is still unclear because the presence of neuroendocrine cells in normal breast has not been proved conclusively”. Moreover they reported two histogenetic hypotheses, the first one stating that “small cell neuroendocrine carcinoma (SCNC is a variant of metaplastic carcinoma arising from a lobular or ductal carcinoma”, the second one claiming that “it is a distinct type of breast carcinoma different from the usual type”. We appreciate this case report and we agree with the authors on the histogenetic diatribe of this rare type of breast neoplasia. In this background, we would highlight our previous case report about a solid variant of mammary adenoid cystic carcinoma merging with "small cell carcinoma" [2] in which we found positivity for CD10 and S100 and negativity for estrogen receptors, both in sbACC and in SCC, in keeping with a myoepithelial origin of both neoplastic areas [3] supporting the hypothesis that the “two components share the same histogenetic myoepithelial origin and represent an example of dedifferentiation along neuroendocrine phenotype lines occurring in a multipotential neoplastic stem line, already committed towards a myoepithelial phenotype”. These findings are in keeping with the first hypothesis about the metaplastic, divergent histogenetic nature of SNSC and we think that this rare SNSC, albeit arising from a different tumor, could be introduced in this case review of the literature, also for its contribute to the histogenetic diatribe.

  11. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

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    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  12. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    International Nuclear Information System (INIS)

    Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

    2013-01-01

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors

  13. Spindle cell thymomas with neuroendocrine morphology: a clinicopathological and immunohistochemical study of 18 cases.

    Science.gov (United States)

    Weissferdt, Annikka; Moran, Cesar A

    2014-07-01

    To present 18 cases of spindle cell thymoma (WHO type A) with prominent neuroendocrine morphology. The patients were nine men and nine women aged 36-76 years (average: 56 years). Clinically, the patients presented with non-specific symptoms such as chest pain, or were entirely asymptomatic. None of the patients had a history of autoimmune syndrome. Surgical resection was performed in all patients. The tumour size ranged from 30 to 110 mm. Macroscopically, the tumours were described as light brown or tan masses with a homogeneous and solid appearance. Microscopically, all tumours showed areas that closely resembled the typical growth pattern of neuroendocrine tumours, i.e. rosette-like structures or a trabecular, insular or ribbon-like arrangement of tumour cells. Areas of more conventional spindle cell thymoma were present in all cases. Seven cases were encapsulated, and 10 cases were invasive tumours. Immunohistochemically, the tumours were positive for pancytokeratin but negative for synaptophysin and chromogranin A. Follow-up information for 10 patients showed that all patients were alive after a period ranging from 1 month to 6 years. Familiarity with this particular pattern of thymoma is important in order to separate this tumour from true neuroendocrine carcinoma and prevent unnecessary adjuvant treatment. © 2014 John Wiley & Sons Ltd.

  14. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

    Directory of Open Access Journals (Sweden)

    Chisato Ohe, MD

    2014-09-01

    Full Text Available Chromophobe renal cell carcinoma (ChRCC with neuroendocrine differentiation/morphology (NED/NEM is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years. One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

  15. Neuron-specific enolase is a useful maker of neuroendocrine origin in pheochromocytoma cell culture

    International Nuclear Information System (INIS)

    Abelin, N.; Dahia, P.L.M.; Martin, R.; Kato, S.; Toledo, S.P.A.

    1994-01-01

    Neuron-specific enolase (NSE) has been used as a marker for neuroendocrine tumors either in immunocytochemical studies or in serum measurements. In this paper NSE levels were determined in cultured pheochromocytoma cells to test whether it is also a useful marker in cell culture of tumors derived from neuroendocrine system. Cultured pheochromocytoma cells came from a primary explant and were grown in RPMI supplemented with 20% fetal calf serum, 100 μg/mL ampicillin and 100 μ/mL streptomycin. NSE was measured in culture medium and cell homogenates. Samples from different pheochromocytoma cultures were analyzed and compared to normal cultured fibroblast cells derived from human skin. NSE was measured by a commercially available radioimmunoassay kit. NSE levels were higher in cell homogenates as compared to those in culture medium, reaching levels as high as 6-fold in the former in TE cell line (26.46 ng/mL and 4.39 ng/mL, respectively). Serial measurements in culture medium from TE cell line evidenced decreasing values in subsequential subcultures (from 9.24 ng/mL during primary explant to 1.7 ng/mL in the tenth subculture). In cultured normal fibroblasts, NSE levels in cultured media were definitely lower than those obtained from pheochromocytoma cultures. These preliminary data suggest that NSE may be a useful marker of neuroendocrine derived tumors, such as pheochromocytoma, in culture. Thus, the simplicity and availability of NSE radioimmunoassay provides an alternative to catecholamine measurement to better characterize pheochromocytoma cell lines in culture, with the advantage of faster result at lower costs. (author). 18 refs, 2 tabs

  16. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

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    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

  17. Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

    Science.gov (United States)

    2018-03-12

    Atypical Carcinoid Tumor; Carcinoid Tumor; Digestive System Neuroendocrine Neoplasm; Enterochromaffin Cell Serotonin-Producing Pancreatic Neuroendocrine Tumor; Functional Pancreatic Neuroendocrine Tumor; Intermediate Grade Lung Neuroendocrine Neoplasm; Low Grade Lung Neuroendocrine Neoplasm; Lung Atypical Carcinoid Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Neuroendocrine Neoplasm; Nonfunctional Pancreatic Neuroendocrine Tumor; Pancreatic Neuroendocrine Tumor; Stage IIIA Digestive System Neuroendocrine Tumor AJCC v7; Stage IIIB Digestive System Neuroendocrine Tumor AJCC v7; Stage IV Digestive System Neuroendocrine Tumor AJCC v7

  18. The Function of Neuroendocrine Cells in Prostate Cancer

    Science.gov (United States)

    2015-06-20

    initiation cells for prostate cancer. Invited Speaker. Steering Committee Meeting, Intestinal Stem Cell Consortium (ISCC). Stowers Institute, Kansas City...unclear. A more recent publication showed that activation ofCXCR2by IL8 leads to cellular senescence, a state of stable proliferative arrest , via a p53...OnelliMR, ShahMH,NicolosoMS, deMartino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer

  19. EVOLUTION OF NEUROENDOCRINE CELL POPULATION AND PEPTIDERGIC INNERVATION, ASSESSED BY DISCRIMINANT ANALYSIS, DURING POSTNATAL DEVELOPMENT OF THE RAT PROSTATE

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    Rosario Rodríguez

    2011-05-01

    Full Text Available Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length on age groups. The following conclusions were drawn: a discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

  20. Neuroendocrine regulation of frog adrenocortical cells by neurotensin

    NARCIS (Netherlands)

    Sicard, F.; D, D.E.G.; Gras, M.; Leprince, J.; Conlon, J.M.; Roubos, E.W.; Vaudry, H.; Delarue, C.

    2005-01-01

    We previously characterized the primary structure of neurotensin (NT) from an extract of the intestine of the frog Rana esculenta. In this study, we provide evidence for the involvement of NT in the neurocrine regulation of the secretory activity of frog adrenocortical cells. Immunohistochemical

  1. Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

    Science.gov (United States)

    Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

    2017-06-01

    The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

  2. Primary large cell neuroendocrine carcinoma of the breast, a case report with an unusual clinical course.

    Science.gov (United States)

    Janosky, Maxwell; Bian, Jessica; Dhage, Shubhada; Levine, Jamie; Silverman, Joshua; Jors, Kathryn; Moy, Linda; Cangiarella, Joan; Muggia, Franco; Adams, Sylvia

    2015-01-01

    Large cell neuroendocrine carcinoma of the breast (NECB) is an extremely rare type of breast cancer; little is known about effective chemotherapies, and data on pathologic response to treatment are unavailable. We report the case of a 34-years-old woman with large cell NECB with initial clinical and pathologic evidence of treatment response to anthracycline-containing neo-adjuvant therapy. Histologic reassessment early during anthracycline chemotherapy revealed cell death with necrosis of 50% of the tumor cells seen in the biopsy specimen. After completing neo-adjuvant chemotherapy, the patient underwent breast-conserving surgery. Pathologic evaluation of the surgical specimen showed a partial response but margins were positive for residual carcinoma. Despite repeated neo-adjuvant chemotherapy, radiotherapy, and surgical resection, the tumor grew rapidly between surgeries and recurred systemically. Therefore, we review the literature on large cell NECB and its treatment options. © 2015 Wiley Periodicals, Inc.

  3. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion.

    Science.gov (United States)

    Barrios, Juliana; Patel, Kruti R; Aven, Linh; Achey, Rebecca; Minns, Martin S; Lee, Yoonjoo; Trinkaus-Randall, Vickery E; Ai, Xingbin

    2017-09-01

    Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating PNEC innervation and secretion of GABA. We found that PNECs were the only cellular source of GABA in airways. In addition, PNECs expressed NT4 as a target-derived mechanism underlying PNEC innervation during development. Early life allergen exposure elevated the level of NT4 and caused PNEC hyperinnervation and nodose neuron hyperactivity. Associated with aberrant PNEC innervation, the authors discovered that GABA hypersecretion was required for the induction of mucin Muc5ac expression. In contrast, NT4 -/- mice were protected from allergen-induced mucus overproduction and changes along the nerve-PNEC axis without any defects in inflammation. Last, GABA installation restored mucus overproduction in NT4 -/- mice after early life allergen exposure. Together, our findings provide the first evidence for NT4-dependent neural regulation of PNEC secretion of GABA in a neonatal disease model. Targeting the nerve-PNEC axis may be a valid treatment strategy for mucus overproduction in airway diseases, such as childhood asthma.-Barrios, J., Patel, K. R., Aven, L., Achey, R., Minns, M. S., Lee, Y., Trinkaus-Randall, V. E., Ai, X. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. © FASEB.

  4. Small-cell neuroendocrine carcinoma of the esophagus: an autopsy case report

    Directory of Open Access Journals (Sweden)

    Mariana Bellaguarda de Castro Sepulvida

    2014-03-01

    Full Text Available Small-cell neuroendocrine carcinoma is a well-known aggressive neoplasia, which is usually associated with a poor prognosis. The lung is the most common primary site, but other organs may be involved, especially those of the digestive tract. The authors report the case of a 71-year-old Caucasian, male patient who was admitted because of congestive heart failure and loss of vision accompanied by right proptosis. Skull and sinuses computed tomography showed a tumoral mass involving the posterior region of the right eye, local bones, and paranasal sinuses. Because of severe hemodynamic instability, the patient died and no diagnostic investigation could be performed. Autopsy findings revealed small-cell neuroendocrine carcinoma of the esophagus and metastases to the posterior region of the right ocular globe, which affected the sinuses, the muscles of the ocular region, the orbit bones, the skull, the meninges and the brain, plus the liver, adrenal glands, and the pericardium. This case called the author’s attention to the extent of the metastatic disease in a patient who was firstly interpreted as presenting solely with congestive heart failure. The autopsy findings substantially aid the understanding of the immediate cause of death.

  5. hGH and GHR expression in large cell neuroendocrine carcinoma of the colon and rectum.

    Science.gov (United States)

    Jukić, Zoran; Limani, Rinë; Luci, Lumturije Gashi; Nikić, Vivian; Mijić, August; Tomas, Davor; Krušlin, Božo

    2012-08-01

    Large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with a low frequency of occurrence in the digestive tract. We present a series of eight patients diagnosed with LCNEC of the colon and rectum. Grossly, tumors were presented as endophytic/ulcerative, annular and polypoid masses, with a gray-white color and necrosis in most cases. Histologically, they were high-grade tumors composed of large cells of organoid, nesting, trabecular, rosette-like and palisading patterns, with a high mitotic rate. Tumors were immunoreactive for neuroendocrine markers, including chromogranin A (2/8), synaptophysin (7/8), and neuron-specific enolase (8/8). Moreover, we analyzed the expression of growth hormone (hGH) and growth hormone receptor (GHR) in colorectal LCNECs and six tumors were immunoreactive for hGH, while five tumors were immunoreactive for GHR. To our knowledge hGH and GHR expression has not been previously analyzed in colorectal LCNEC. Their overexpression suggests a role of hGH and GHR in the development of colorectal LCNEC.

  6. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom

    2016-02-05

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

  7. Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

    Science.gov (United States)

    Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

    2017-09-01

    The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

  8. Morpho-functional architecture of the Golgi complex of neuroendocrine cells

    Directory of Open Access Journals (Sweden)

    Emma eMartínez-Alonso

    2013-03-01

    Full Text Available In neuroendocrine cells, prohormones move from the endoplasmic reticulum to the Golgi complex, where they are sorted and packed into secretory granules. The Golgi complex is considered the central station of the secretory pathway of proteins and lipids en route to their final destination. In most mammalian cells, it is formed by several stacks of cisternae connected by tubules, forming a continuous ribbon. This organelle shows an extraordinary structural and functional complexity, which is exacerbated by the fact that its architecture is cell type-specific and also tuned by the functional status of the cell. It is, indeed, one the most beautiful cellular organelles and, for that reason, perhaps the most extensively photographed by electron microscopists. In recent decades, an exhaustive dissection of the molecular machinery involved in membrane traffic and other Golgi functions has been carried out. Concomitantly, detailed morphological studies have been performed, including 3D analysis by electron tomography, and the precise location of key proteins has been identified by immunoelectron microscopy. Despite all this effort, some basic aspects of Golgi functioning remain unsolved. For instance, the mode of intra-Golgi transport is not known, and two opposing theories (vesicular transport and cisternal maturation models have polarized the field for many years. Neither of these theories explains all the experimental data so that new theories and combinations thereof have recently been proposed. Moreover, the specific role of the small vesicles and tubules which surround the stacks needs to be clarified. In this review, we summarize our current knowledge of the Golgi architecture in relation with its function and the mechanisms of intra-Golgi transport. Within the same framework, the characteristics of the Golgi complex of neuroendocrine cells are analyzed.

  9. Signet ring cell neuroendocrine tumor liver with mesenteric metastasis: Description of a rare phenomenon, with literature review

    Directory of Open Access Journals (Sweden)

    Sheefa Haq

    2015-01-01

    Full Text Available Primary hepatic signet ring cell neuroendocrine tumor (NET is extremely rare, and may show both neuroendocrine and glandular differentiation. Unlike the usual signet ring cells of adenocarcinoma, these cells are characterized by mucin negative, cytokeratin and chromogranin positive intracytoplasmic vacuoles resembling signet ring cells. These tumors are usually well demarcated surgically resectable lesions. To the best of our knowledge, we report the fifth case of primary hepatic signet ring cell NET, with the present case bearing multiple hepatic space occupying lesions and mesenteric metastasis. Due to very few isolated reports, prognosis of NET with signet ring cell morphology is largely unknown. Documentation of this case with review of related literature may enrich the existing knowledge regarding the outcome and management of this rare tumor.

  10. Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma.

    Science.gov (United States)

    Tsai, Harrison K; Lehrer, Jonathan; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L

    2017-11-13

    Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis. Moreover, past studies have focused on prototypical NEPC samples with classic immunohistochemistry profiles, whereas there is increasing recognition of atypical phenotypes. In the primary setting, small cell prostatic carcinoma (SCPC) is frequently admixed with adenocarcinomas that may be clonally related, and a minority of SCPCs express markers typical of prostatic adenocarcinoma while rare cases do not express neuroendocrine markers. We derived a meta-signature of prototypical high-grade NEPC, then applied it to develop a classifier of primary SCPC incorporating disease heterogeneity. Prototypical NEPC samples from 15 patients across 6 frozen tissue microarray datasets were assessed for genes with consistent outlier expression relative to adenocarcinomas. Resulting genes were used to determine subgroups of primary SCPCs (N=16) and high-grade adenocarcinomas (N=16) profiled by exon arrays using formalin-fixed paraffin-embedded (FFPE) material from our institutional archives. A subgroup classifier was developed using differential expression for feature selection, and applied to radical prostatectomy cohorts. Sixty nine and 375 genes demonstrated consistent outlier expression in at least 80% and 60% of NEPC patients, with close resemblance in expression between NEPC and small cell lung cancer. Clustering by these genes generated 3 subgroups among primary samples from our institution. Nearest centroid classification based on the predominant phenotype from each

  11. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Directory of Open Access Journals (Sweden)

    Sangbin Park

    2011-08-01

    Full Text Available Drosophila neuroendocrine cells comprising the corpora cardiaca (CC are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  12. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia of the Lung (DIPNECH): Current Best Evidence.

    Science.gov (United States)

    Wirtschafter, Eric; Walts, Ann E; Liu, Sandy T; Marchevsky, Alberto M

    2015-10-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.

  13. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

    Science.gov (United States)

    Lee, John K.; Phillips, John W.; Smith, Bryan A.; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F.; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G.; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Shokat, Kevan M.; Gustafson, W. Clay; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    SUMMARY MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  14. Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report

    Directory of Open Access Journals (Sweden)

    Jiang Shi-Xu

    2010-11-01

    Full Text Available Abstract Thymic large cell neuroendocrine carcinomas (LCNECs are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.

  15. Histone H1x is highly expressed in human neuroendocrine cells and tumours

    International Nuclear Information System (INIS)

    Warneboldt, Julia; Haller, Florian; Horstmann, Olaf; Danner, Bernhard C; Füzesi, László; Doenecke, Detlef; Happel, Nicole

    2008-01-01

    Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation. Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study. We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues. We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate

  16. Neuroendocrine aspects of prostate oncogenesis

    Directory of Open Access Journals (Sweden)

    P.V. Glybochko

    2010-03-01

    Full Text Available The prostate cancer is a widespread disease in Russia with high growth rate and high death rate. Active work in discovery of methods of early diagnostics of prostate cancer is carrying out. it will allow to increase considerably the efficiency of treatment. the data on topography, structural and functional organization, physiology and regulatory effect of neuroendocrine cells and neuroendocrine hormones and peptides of prostate produced by neuroendocrine cells are presented in the review. Neuroendocrine mechanisms of development, prospects of early diagnostics and prognosis of prostate cancer are analyzed

  17. Acute damage by naphthalene triggers expression of the neuroendocrine marker PGP9.5 in airway epithelial cells

    DEFF Research Database (Denmark)

    Poulsen, T.T.; Naizhen, X.; Linnoila, R.I.

    2008-01-01

    Protein Gene Product 9.5 (PGP9.5) is highly expressed in nervous tissue. Recently PGP9.5 expression has been found to be upregulated in the pulmonary epithelium of smokers and in non-small cell lung cancer, suggesting that it also plays a role in carcinogen-inflicted lung epithelial injury...... neuroendocrine markers was found in the non-neuroendocrine epithelial cells after naphthalene exposure. In contrast, immunostaining for the cell cycle regulator p27(Kip1), which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27(Kip1) in naphthalene exposed...... and further strengthens the accumulating evidence of PGP9.5 as a central player in lung epithelial damage and early carcinogenesis Udgivelsesdato: 2008/9/26...

  18. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  19. Immunohistochemical Analysis of Neuroendocrine (NE) Differentiation in Testicular Germ Cell Tumors (GCTs): Use of Confocal Laser Scanning Microscopy (CLSM) to Demonstrate Direct NE Differentiation from GCTs

    International Nuclear Information System (INIS)

    Kumaki, Nobue; Umemura, Shinobu; Kajiwara, Hiroshi; Itoh, Johbu; Itoh, Yoshiko; Osamura, R.Yoshiyuki

    2007-01-01

    Neuroendocrine (NE) differentiation is infrequent in testicular tumors and its histogenesis is not well understood. The present study is aimed at elucidating the pathway of neuroendocrine differentiation in germ cell tumors (GCTs) of the testis. In the analysis of 46 germ cell tumor components from 23 testicular tumors, we focused on GCTs with neuroendocrine differentiation, 7 teratoma, 1 embryonal carcinoma and 1 neuroendocrine carcinoma by immunohistochemical study and confocal laser scanning microscopy (CLSM) analysis. NE marker positive cells were noted in the tumor with collision of teratoma and embryonal carcinoma (E&T tumor), in the immature columnar cells of transitional form of embryonal carcinoma to teratoma (E-T cells) and neuroendocrine carcinoma cells, in addition to the well known mature intestinal mucosa in teratoma. Double staining for a NE marker (CGA) and a germ cell marker (PLAP) demonstrated the localization of both proteins in the same E-T cells confirmed by CLSM. Another finding, indicating the intimate relation between embryonal carcinoma and neuroendcrine differentiation, is that neuroendocrine carcinoma expressed a marker of embryonal carcinoma, CD30. The present results indicated that the NE cells might be differentiated from embryonal carcinoma, a view that has not been proposed before, but that is made in the present study using CLSM

  20. Progesterone arrested cell cycle progression through progesterone receptor isoform A in pancreatic neuroendocrine neoplasm.

    Science.gov (United States)

    Yazdani, Samaneh; Kasajima, Atsuko; Onodera, Yoshiaki; McNamara, Keely May; Ise, Kazue; Nakamura, Yasuhiro; Tachibana, Tomoyoshi; Motoi, Fuyuhiko; Unno, Michiaki; Sasano, Hironobu

    2018-04-01

    In pancreatic neuroendocrine neoplasms (Pan-NEN) progesterone signaling has been shown to have both inhibitory and stimulatory effects on cell proliferation. The ability of progesterone to inhibit tumor proliferation is of particular interest and is suggested to be mediated through the less abundantly expressed progesterone receptor (PR) isoform A (PRA). To date the mechanistic processes underlying this inhibition of proliferation remain unclear. To examine the mechanism of PRA actions, the human Pan-NEN cell line QGP-1, that endogenously expresses PR isoform B (PRB) without PRA, was transfected with PRA. PRA transfection suppressed the majority of cell cycle related genes increased by progesterone including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2). Importantly, following progesterone administration cell cycle distribution was shifted to S and G2/M phases in the naïve cell line but in PRA-transfected cells, this effect was suppressed. To see if these mechanistic insights were confirmed in patient samples PRA, PRB, CCNA2, CCNB, CDK1 and CDK2 immunoreactivities were assessed in Pan-NEN cases. Higher levels of cell cycle markers were associated with higher WHO grade tumors and correlations between the markers suggested formation of cyclin/CDK activated complexes in S and G2/M phases. PRA expression was associated with inverse correlation of all cell cycle markers. Collectively, these results indicate that progesterone signals through PRA negatively regulates cell cycle progression through suppressing S and G2/M phases and downregulation of cell cycle phases specific cyclins/CDKs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    H. IJsselstijn (Hanneke); N. Hung; J.C. de Jongste (Johan); D. Tibboel (Dick); E. Cutz

    1998-01-01

    textabstractCongenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We

  2. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

    Science.gov (United States)

    Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

    2016-01-01

    Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

  3. The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

    Science.gov (United States)

    Labrecque, Mark P.; Takhar, Mandeep K.; Nason, Rebecca; Santacruz, Stephanie; Tam, Kevin J.; Massah, Shabnam; Haegert, Anne; Bell, Robert H.; Altamirano-Dimas, Manuel; Collins, Colin C.; Lee, Frank J.S.; Prefontaine, Gratien G.; Cox, Michael E.; Beischlag, Timothy V.

    2016-01-01

    Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role Rb plays in mediating hypoxia-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that loss of Rb in conjunction with hypoxia leads to aberrant expression of hypoxia-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. PMID:27015368

  4. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    Science.gov (United States)

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  5. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome.

    Science.gov (United States)

    Elsenbruch, Sigrid; Lucas, Ayscha; Holtmann, Gerald; Haag, Sebastian; Gerken, Guido; Riemenschneider, Natalie; Langhorst, Jost; Kavelaars, Annemieke; Heijnen, Cobi J; Schedlowski, Manfred

    2006-10-01

    Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls. Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls. At baseline, immediately following public speaking, and after a recovery period, state anxiety, acute GI symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic hormone (ACTH) were measured, and numbers of circulating leukocytes and lymphocyte subpopulations were analyzed by flow cytometry. Public speaking led to significant cardiovascular activation, a significant increase in ACTH, and a redistribution of circulating leukocytes and lymphocyte subpopulations, including significant increases in natural killer cells and cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater state anxiety both at baseline and following public speaking. However, cardiovascular and endocrine responses, as well as the redistribution of circulating leukocytes and lymphocyte subpopulations after public speaking stress, did not differ for IBS patients compared with controls. In IBS patients without psychiatric comorbidity, the endocrine response as well as the circulation pattern of leukocyte subpopulations to acute psychosocial stress do not differ from healthy controls in spite of enhanced emotional responses. Future studies should discern the role of psychopathology in psychological and biological stress responses in IBS.

  6. Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland.

    Science.gov (United States)

    Andreasen, Simon; Persson, Marta; Kiss, Katalin; Homøe, Preben; Heegaard, Steffen; Stenman, Göran

    2016-04-01

    A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC. The patient died of her lung cancer after 19 months without evidence of recurrence of the LCNEC. Genomic profiling of the salivary gland LCNEC revealed a hypodiploid genome predominated by losses of whole chromosomes or chromosome arms involving chromosomes 3p, 4, 7q, 10, 11, 13, 16q and gains of 3q and 16p. In addition, there was a segmental gain of 9p23-p22.3 including the NFIB oncogene. Continued studies of salivary gland LCNEC may provide new knowledge concerning potential diagnostic biomarkers and may ultimately also lead to the identification of new treatment targets for patients with these aggressive carcinomas.

  7. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  8. Mating-Induced Increase in Germline Stem Cells via the Neuroendocrine System in Female Drosophila.

    Science.gov (United States)

    Ameku, Tomotsune; Niwa, Ryusuke

    2016-06-01

    Mating and gametogenesis are two essential components of animal reproduction. Gametogenesis must be modulated by the need for gametes, yet little is known of how mating, a process that utilizes gametes, may modulate the process of gametogenesis. Here, we report that mating stimulates female germline stem cell (GSC) proliferation in Drosophila melanogaster. Mating-induced increase in GSC number is not simply owing to the indirect effect of emission of stored eggs, but rather is stimulated by a male-derived Sex Peptide (SP) and its receptor SPR, the components of a canonical neuronal pathway that induces a post-mating behavioral switch in females. We show that ecdysteroid, the major insect steroid hormone, regulates mating-induced GSC proliferation independently of insulin signaling. Ovarian ecdysteroid level increases after mating and transmits its signal directly through the ecdysone receptor expressed in the ovarian niche to increase the number of GSCs. Impairment of ovarian ecdysteroid biosynthesis disrupts mating-induced increase in GSCs as well as egg production. Importantly, feeding of ecdysteroid rescues the decrease in GSC number caused by impairment of neuronal SP signaling. Our study illustrates how female GSC activity is coordinately regulated by the neuroendocrine system to sustain reproductive success in response to mating.

  9. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Diez Soraya

    2010-03-01

    Full Text Available Abstract Background Wnt-11 is a secreted protein that modulates cell growth, differentiation and morphogenesis during development. We previously reported that Wnt-11 expression is elevated in hormone-independent prostate cancer and that the progression of prostate cancer from androgen-dependent to androgen-independent proliferation correlates with a loss of mutual inhibition between Wnt-11- and androgen receptor-dependent signals. However, the prevalence of increased expression of Wnt-11 in patient tumours and the functions of Wnt-11 in prostate cancer cells were not known. Results Wnt-11 protein levels in prostate tumours were determined by immunohistochemical analysis of prostate tumour tissue arrays. Wnt-11 protein was elevated in 77/117 of tumours when compared with 27 benign prostatic hypertrophy specimens and was present in 4/4 bone metastases. In addition, there was a positive correlation between Wnt-11 expression and PSA levels above 10 ng/ml. Androgen-depleted LNCaP prostate cancer cells form neurites and express genes associated with neuroendocrine-like differentiation (NED, a feature of prostate tumours that have a poor prognosis. Since androgen-depletion increases expression of Wnt-11, we examined the role of Wnt-11 in NED. Ectopic expression of Wnt-11 induced expression of NSE and ASCL1, which are markers of NED, and this was prevented by inhibitors of cyclic AMP-dependent protein kinase, consistent with the known role of this kinase in NED. In contrast, Wnt-11 did not induce NSE expression in RWPE-1 cells, which are derived from benign prostate, suggesting that the role of Wnt-11 in NED is specific to prostate cancer. In addition, silencing of Wnt-11 expression in androgen-depleted LNCaP cells prevented NED and resulted in apoptosis. Silencing of Wnt-11 gene expression in androgen-independent PC3 cells also reduced expression of NSE and increased apoptosis. Finally, silencing of Wnt-11 reduced PC3 cell migration and ectopic

  10. The Light Green Cells of Lymnaea: a neuroendocrine model system for stimulus-induced expression of multiple peptide genes in a single cell type

    NARCIS (Netherlands)

    Geraerts, W. P.; Smit, A. B.; Li, K. W.; Hordijk, P. L.

    1992-01-01

    We review recent experiments showing that the cerebral neuroendocrine Light Green Cells (LGCs) of the freshwater snail, Lymnaea stagnalis, express a family of distinct though related molluscan insulin-related peptide (MIP) genes. The LGCs are involved in the regulation of a wide range of

  11. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  12. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium.

    Science.gov (United States)

    Weichselbaum, Markus; Sparrow, Malcolm P; Hamilton, Elisha J; Thompson, Philip J; Knight, Darryl A

    2005-10-10

    Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1) undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5), sensory nerves (calcitonin gene related peptide, CGRP), and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP). The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP) was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  13. Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila.

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    Jiangnan Luo

    Full Text Available Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM. Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B, whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin signaling components, such as Rheb (small GTPase, TOR and S6K (S6 kinase. After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.

  14. Focal adhesion kinase, a downstream mediator of Raf-1 signaling, suppresses cellular adhesion, migration, and neuroendocrine markers in BON carcinoid cells.

    Science.gov (United States)

    Ning, Li; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2010-05-01

    We have recently reported that activation of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade in gastrointestinal carcinoid cell line (BON) alters cellular morphology and neuroendocrine phenotype. The mechanisms by which Raf-1 mediates these changes in carcinoid cells are unclear. Here, we report that activation of the Raf-1 signaling cascade in BON cells induced the expression of focal adhesion kinase (FAK) protein, suppressed the production of neuroendocrine markers, and resulted in significant decreases in cellular adhesion and migration. Importantly, inactivation of MEK1/2 by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene or abolition of FAK induction in Raf-1-activated BON cells by targeted siRNA led to reversal of the Raf-1-mediated reduction in neuroendocrine markers and cellular adhesion and migration. Phosphorylation site-specific antibodies detected the phosphorylated FAK(Tyr407), but not FAK(Tyr397), in these Raf-1-activated cells, indicating that FAK(Tyr407) may be associated with changes in the neuroendocrine phenotype. Overexpression of constitutively active FAK plasmids (wild-type FAK or FAK(Tyr397) mutant) into BON cells reduced neuroendocrine markers, whereas the FAK(Tyr407) mutant plasmid did not show any decrease in the levels of neuroendocrine markers, indicating that phosphorylation of FAK at the Tyr(407) residue may be important for these effects. Our results showed for the first time that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulated the neuroendocrine and metastatic phenotype in BON cells. (c)2010 AACR.

  15. Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258 and its Therapeutic Implications

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    Shalini S. Yadav

    2017-06-01

    Full Text Available Prostate cancer (PCa remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT; however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC. With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC. This, along with previous observations of an increase in the number of such NE cells in aggressive tumors, has been suggested as a mechanism of resistance development during prostate cancer progression. Dovitinib (TKI-258/CHIR-258 is a pan receptor tyrosine kinase (RTK inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It has shown efficacy in mouse-model of PCa bone metastasis, and is presently in clinical trials for several cancers. We observed that both androgen receptor (AR positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. The NE differentiation was also observed when mice harboring PC3-xenografted tumors were systemically treated with Dovitinib. The mechanistic underpinnings of this differentiation are unclear, but seem to be supported through MAPK-, PI3K-, and Wnt-signaling pathways. Further elucidation of the differentiation process will enable the identification of alternative salvage or combination therapies to overcome the potential resistance development.

  16. Overcrowding-mediated stress alters cell proliferation in key neuroendocrine areas during larval development in Rhinella arenarum.

    Science.gov (United States)

    Distler, Mijal J; Jungblut, Lucas D; Ceballos, Nora R; Paz, Dante A; Pozzi, Andrea G

    2016-02-01

    Exposure to adverse environmental conditions can elicit a stress response, which results in an increase in endogenous corticosterone levels. In early life stages, it has been thoroughly demonstrated that amphibian larval growth and development is altered as a consequence of chronic stress by interfering with the metamorphic process, however, the underlying mechanisms involved have only been partially disentangled. We examined the effect of intraspecific competition on corticosterone levels during larval development of the toad Rhinella arenarum and its ultimate effects on cell proliferation in particular brain areas as well as the pituitary gland. While overcrowding altered the number of proliferating cells in the pituitary gland, hypothalamus, and third ventricle of the brain, no differences were observed in areas which are less associated with neuroendocrine processes, such as the first ventricle of the brain. Apoptosis was increased in hypothalamic regions but not in the pituitary. With regards to pituitary cell populations, thyrotrophs but not somatoatrophs and corticotrophs showed a decrease in the cell number in overcrowded larvae. Our study shows that alterations in growth and development, produced by stress, results from an imbalance in the neuroendocrine systems implicated in orchestrating the timing of metamorphosis. © 2016 Wiley Periodicals, Inc.

  17. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

    Science.gov (United States)

    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  18. Endocannabinoid Regulation of Neuroendocrine Systems.

    Science.gov (United States)

    Tasker, Jeffrey G; Chen, Chun; Fisher, Marc O; Fu, Xin; Rainville, Jennifer R; Weiss, Grant L

    2015-01-01

    The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus. Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems. Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function. Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C. The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964). © 2015 Elsevier Inc. All rights reserved.

  19. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  20. The demonstration of pulmonary neuroendocrine cell hyperplasia with tumorlets in a patient with chronic cough and a history of multiple medical problems.

    Science.gov (United States)

    Carmichael, Mark G; Zacher, Lisa L

    2005-05-01

    A 58-year-old woman presented with chronic cough felt to be multifactorial secondary to asthma, gastroesophageal reflux disease, and chronic sinusitis. Additional medical history included obstructive sleep apnea, type 2 diabetes, and hypertension. She had a 40- year history of tobacco use, but quit 10 years ago. Her examination was significant for obesity and cobble stoning of the oropharynx. Pulmonary function testing and arterial blood gases were unrevealing. Chest films were normal. High-resolution computed tomography revealed multiple focal lucencies in a mosaic pattern consistent with air trapping and small airways disease. Bronchoscopy revealed normal airways and a noninflammatory bronchoalveolar lavage. Transbronchial biopsies revealed inflammatory infiltrates of the peribronchiolar interstitium. Lung biopsy revealed pulmonary neuroendocrine cell hyperplasia with tumorlets that stained positive for neuroendocrine tissue. We present the case of a woman with chronic cough, multiple medical problems, and pulmonary neuroendocrine cell hyperplasia with tumorlets.

  1. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  2. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Odagiri, Kazumasa; Omura, Motoko; Hata, Masaharu; Aida, Noriko; Niwa, Tetsu; Ogino, Ichiro; Kigasawa, Hisato; Ito, Susumu; Adachi, Masataka; Inoue, Tomio

    2012-01-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6–19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18–203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients

  3. Neuroendocrine breast cancer.

    Science.gov (United States)

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-08-13

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.

  4. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  5. Neuroendocrine Role for VGF

    Directory of Open Access Journals (Sweden)

    Jo Edward Lewis

    2015-02-01

    Full Text Available The vgf gene (non-acronymic is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain derived neurotrophic factor, and glial derived growth factor. The VGF gene gives rise to a 68kDa precursor polypeptide which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific pro-hormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly the hypothalamus and hippocampus, and in peripheral tissues including the pituitary gland, the adrenal glands and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles and in this mini-review we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction and cognition.

  6. Manipulation of [C-11]-5-hydroxytryptophan and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells

    NARCIS (Netherlands)

    Neels, Oliver C.; Koopmans, Klaas P.; Jager, Pieter L.; Vercauteren, Laya; van Waarde, Aren; Doorduin, Janine; Timmer-Bosscha, Hetty; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.; Dierckx, Rudi A. J. O.; Kema, Ido P.; Elsinga, Philip H.

    2008-01-01

    [C-11]-5-Hydroxytryptophan ([C-11]HTP) and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine [F-18]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large

  7. Rapid Nongenomic Glucocorticoid Actions in Male Mouse Hypothalamic Neuroendocrine Cells Are Dependent on the Nuclear Glucocorticoid Receptor

    Science.gov (United States)

    Nahar, Jebun; Haam, Juhee; Chen, Chun; Jiang, Zhiying; Glatzer, Nicholas R.; Muglia, Louis J.; Dohanich, Gary P.; Herman, James P.

    2015-01-01

    Corticosteroids act classically via cognate nuclear receptors to regulate gene transcription; however, increasing evidence supports rapid, nontranscriptional corticosteroid actions via activation of membrane receptors. Using whole-cell patch clamp recordings in hypothalamic slices from male mouse genetic models, we tested for nongenomic glucocorticoid actions at glutamate and gamma aminobutyric acid (GABA) synapses in hypothalamic neuroendocrine cells, and for their dependence on the nuclear glucocorticoid receptor (GR). In enhanced green fluorescent protein-expressing CRH neurons of the paraventricular nucleus (PVN) and in magnocellular neurons of the PVN and supraoptic nucleus (SON), dexamethasone activated postsynaptic membrane-associated receptors and G protein signaling to elicit a rapid suppression of excitatory postsynaptic inputs, which was blocked by genetic deletion of type I cannabinoid receptors and a type I cannabinoid receptor antagonist. In magnocellular neurons, dexamethasone also elicited a rapid nitric oxide-dependent increase in inhibitory postsynaptic inputs. These data indicate a rapid, synapse-specific glucocorticoid-induced retrograde endocannabinoid signaling at glutamate synapses and nitric oxide signaling at GABA synapses. Unexpectedly, the rapid glucocorticoid effects on both excitatory and inhibitory synaptic transmission were lost with conditional deletion of GR in the PVN and SON in slices from a single minded-1-cre-directed conditional GR knockout mouse. Thus, the nongenomic glucocorticoid actions at glutamate and GABA synapses on PVN and SON neuroendocrine cells are dependent on the nuclear GR. The nuclear GR, therefore, is responsible for transducing the rapid steroid response at the membrane, or is either a critical component in the signaling cascade or regulates a critical component of the signaling cascade of a distinct membrane GR. PMID:26061727

  8. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  9. Primary Small Cell Neuroendocrine Carcinoma of the Nasal Cavity After Successful Curative Therapy of Nasopharyngeal Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Chien-Heng Lin

    2009-03-01

    Full Text Available Patients with head and neck cancer have a greater risk of developing second primary malignant neoplasms than patients with any other type of malignancy. Small cell neuroendocrine carcinoma (SNEC mainly occurs in the lung, and is rarely found in the head and neck region. Only a few cases of sinonasal SNEC have been reported in the English literature. A woman aged 53 years, who had undergone successful curative radiotherapy for nasopharyngeal carcinoma 10 years earlier, presented with a history of bleeding from the left nostril for several weeks. A computed tomography scan of the head and neck showed a mass in the left nasal cavity with extension into the maxillary sinus. A biopsy specimen was taken and pathology revealed SNEC. The patient underwent a full course of concurrent chemoradiotherapy. No local recurrence or distant metastasis was noted during the 12 months of follow-up.

  10. Neuroendocrine Cell Carcinoma of Unknown Primary Arising in Long Standing History of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stergios Boussios

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS. Cancer of unknown primary site (CUP is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS.

  11. Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats.

    Science.gov (United States)

    Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A

    2015-07-01

    Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells. © 2014 by The Author(s).

  12. The effect of transforming growth factor beta on human neuroendocrine tumor BON cell proliferation and differentiation is mediated through somatostatin signaling.

    Science.gov (United States)

    Leu, Frank P; Nandi, Minesh; Niu, Congrong

    2008-06-01

    The dual effect of the ubiquitous inflammatory cytokine transforming growth factor beta1 (TGF beta) on cellular proliferation and tumor metastasis is intriguing but complex. In epithelial cell- and neural cell-derived tumors, TGF beta serves as a growth inhibitor at the beginning of tumor development but later becomes a growth accelerator for transformed tumors. The somatostatin (SST) signaling pathway is a well-established antiproliferation signal, and in this report, we explore the interplay between the SST and TGF beta signaling pathways in the human neuroendocrine tumor cell line BON. We defined the SST signaling pathway as a determinant for neuroendocrine tumor BON cells in responding to TGF beta as a growth inhibitor. We also determined that TGF beta induces the production of SST and potentially activates the negative growth autocrine loop of SST, which leads to the downstream induction of multiple growth inhibitory effectors: protein tyrosine phosphatases (i.e., SHPTP1 and SHPTP2), p21(Waf1/Cip1), and p27(Kip1). Concurrently, TGF beta down-regulates the growth accelerator c-Myc protein and, collectively, they establish a firm antiproliferation effect on BON cells. Additionally, any disruption in the activation of either the TGF beta or SST signaling pathway in BON leads to "reversible" neuroendocrine-mesenchymal transition, which is characterized by the loss of neuroendocrine markers (i.e., chromogranin A and PGP 9.5), as well as the altered expression of mesenchymal proteins (i.e., elevated vimentin and Twist and decreased E-cadherin), which has previously been associated with elevated metastatic potential. In summary, TGF beta-dependent growth inhibition and differentiation is mediated by the SST signaling pathway. Therefore, any disruption of this TGF beta-SST connection allows BON cells to respond to TGF beta as a growth accelerator instead of a growth suppressor. This model can potentially apply to other cell types that exhibit a similar interaction of

  13. Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

    Science.gov (United States)

    Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

    2016-04-01

    Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  15. Neuroendocrine dysfunction in Sjogren's syndrome.

    Science.gov (United States)

    Tzioufas, Athanasios G; Tsonis, John; Moutsopoulos, Haralampos M

    2008-01-01

    Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations

  16. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Sørensen, Flemming Brandt

    2005-01-01

    tumors. Western blotting, immunohistochemistry, immunofluorescence microscopy and ELISA were applied. Western blot analysis detected a 32-kDa secretagogin band in samples from normal mucosa. Immunohistochemical analyses on tissue specimens showed that secretagogin is exclusively expressed...... in neuroendocrine cells and nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign hyperplasic polyps and adenomas showed a decreased number of secretagogin-expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine markers (chromogranin A, neuron-specific enolase......, synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas...

  17. Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.

    Science.gov (United States)

    Delk, Nikki A; Farach-Carson, Mary C

    2012-04-01

    Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

  18. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  19. Examining changes in cellular communication in neuroendocrine cells after noble metal nanoparticle exposure.

    Science.gov (United States)

    Love, Sara A; Liu, Zhen; Haynes, Christy L

    2012-07-07

    As nanoparticles enjoy increasingly widespread use in commercial applications, the potential for unintentional exposure has become much more likely during any given day. Researchers in the field of nanotoxicity are working to determine the physicochemical nanoparticle properties that lead to toxicity in an effort to establish safe design rules. This work explores the effects of noble metal nanoparticle exposure in murine chromaffin cells, focusing on examining the effects of size and surface functionality (coating) in silver and gold, respectively. Carbon-fibre microelectrode amperometry was utilized to examine the effect of exposure on exocytosis function, at the single cell level, and provided new insights into the compromised functions of cells. Silver nanoparticles of varied size, between 15 and 60 nm diameter, were exposed to cells and found to alter the release kinetics of exocytosis for those cells exposed to the smallest examined size. Effects of gold were examined after modification with two commonly used 'bio-friendly' polymers, either heparin or poly (ethylene glycol), and gold nanoparticles were found to induce altered cellular adhesion or the number of chemical messenger molecules released, respectively. These results support the body of work suggesting that noble metal nanoparticles perturb exocytosis, typically altering the number of molecules and kinetics of release, and supports a direct disruption of the vesicle matrix by the nanoparticle. Overall, it is clear that various nanoparticle physicochemical properties, including size and surface coating, do modulate changes in cellular communication via exocytosis.

  20. Senso-Neuroendocrine Cells Within The Cerebral Ganglion Of The Earthworm Aporrectodea Caliginosa

    OpenAIRE

    Al Yousuf, Shoa'a [شعاع السيد اليوسف

    1992-01-01

    Ciliated neurones of probable endocrine function are present inside and outside the cerebral ganglion of the earthworm Aporrectodea caliginosa. Cell fibers contain clusters ofsynaptoid vesicles in regions adjacent to the brain capsule or muscles. The cell bodies also send axons to terminate within the neuropile, where synapses and exocytosis of their secretory granules occur. Cytochemical studies indicate the presence of catecholamines within these granules. باستخدام المجهر الالكتروني النف...

  1. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Floridon, C.; Jensen, C.H.; Thorsen, P.

    2000-01-01

    -embryonic tissues from normal and pathological pregnancies revealed FA1 in stromal cells surrounding the blood islands of the yolk sac as well as in placental fibroblasts where the expression was most pronounced in diploid, androgenic complete hydatidiform moles. However, as measured by ELISA, the circulating...

  2. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis.

    Science.gov (United States)

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management.

  3. High glucose induces N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 T-type calcium channels in neuroendocrine-like differentiated human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Kazuki Fukami

    2017-01-01

    Full Text Available Given that Cav3.2 T-type Ca2+ channels were functionally regulated by asparagine (N-linked glycosylation, we examined effects of high glucose on the function of Cav3.2, known to regulate secretory function, in neuroendocrine-like differentiated prostate cancer LNCaP cells. High glucose accelerated the increased channel function and overexpression of Cav3.2 during neuroendocrine differentiation, the former prevented by enzymatic inhibition of N-glycosylation and cleavage of N-glycans. Hyperglycemia thus appears to induce N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 in neuroendocrine-like differentiated prostate cancer cells.

  4. A bipartite graph of Neuroendocrine System

    Science.gov (United States)

    Guo, Zhong-Wei; Zou, Sheng-Rong; Peng, Yu-Jing; Zhou, Ta; Gu, Chang-Gui; He, Da-Ren

    2008-03-01

    We present an empirical investigation on the neuroendocrine system and suggest describe it by a bipartite graph. In the net the cells can be regarded as collaboration acts and the mediators can be regarded as collaboration actors. The act degree stands for the number of the cells that secrete a single mediator. Among them bFGF (the basic fibroblast growth factor) has the largest node act degree. It is the most important mitogenic cytokine, followed by TGF-beta, IL-6, IL1-beta, VEGF, IGF-1and so on. They are critical in neuroendocrine system to maintain bodily healthiness, emotional stabilization and endocrine harmony. The act degree distribution shows a shifted power law (SPL) function forms [1]. The average act degree of neuroendocrine network is h=3.01, It means that each mediator is secreted by three cells on average. The similarity, which stands for the average probability of secreting the same mediators by all neuroendocrine cells, is observed as s=0.14. Our results may be used in the research of the medical treatment of neuroendocrine diseases. [1] Assortativity and act degree distribution of some collaboration networks, Hui Chang, Bei-Bei Su, Yue-Ping Zhou, Daren He, Physica A, 383 (2007) 687-702

  5. Ontogenesis of the reticulum with special reference to neuroendocrine and glial cells: a comparative analysis of the Merino sheep and Iberian red deer.

    Science.gov (United States)

    Franco, A; Masot, J; García, A; Redondo, E

    2012-10-01

    The present study was designed to compare the differences in the ontogenesis of the reticulum in sheep (domestic ruminant) and deer (wild ruminant). A total of 50 embryos and foetuses Merino sheep and 50 Iberian deer were used, from the first pre-natal life until birth. The appearance of the reticulum from the primitive gastric tube was earlier in the sheep (22% gestation, 33 days) than in the deer (25% gestation, 66 days). In both cases, it displayed a primitive epithelium of a stratified, cylindrical, non-ciliary type. At around 48% gestation in the sheep (72 days) and 36% (97 days) in the deer, the reticulum was configured of four clearly differentiated layers: mucosa (with epithelial layer and lamina propria), submucosa, tunica muscularis and serosa. The stratification of the epithelial layer was accompanied by modifications in its structure with the appearance of the primitive reticular ribs. The primary ribs began to be formed first in the deer, at 117 days of pre-natal life (40% gestation) and later in the sheep (79 days, 53% gestation). The differentiation of the corneum papillae in the primary ribs coincided with the appearance of secondary reticular ribs. These structures began to be formed first in the deer, at 142 days of pre-natal life (51% gestation) and later in the sheep (83 days, 55% gestation). The presence of neuroendocrine cells (non-neuronal enolase-positive cells) in the reticular mucosa was not detected until 97 days (36% gestation) in deer and 81 days (54% gestation) in sheep. The presence of glial cells (GFAP-positive cells) occurred at around 142 days (51% gestation) in deer and at 112 days (75% gestation) in sheep. In conclusion, the presence of neuroendocrine and glial cells was detected in deer at earlier stages than sheep. © 2012 Blackwell Verlag GmbH.

  6. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    neuroendocrine carcinoma (NEC) of the breast as having more than 50% neoplastic tumor cells expressing neuroendocrine. (NE) markers.[2] These tumors are usually seen in elderly women around sixth or seventh decade of life as reported in literatures.[1,3] Herein we report a case of primary NCE of breast in a middle ...

  7. A short history of neuroendocrine tumours and their peptide hormones

    DEFF Research Database (Denmark)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark

    2016-01-01

    The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The panc...

  8. Targeting neuroendocrine differentiation for prostate cancer radiosensitization

    Science.gov (United States)

    2017-12-01

    progression. Prostate, 2007. 67(7): p. 764-73. 17. Deeble, P.D., et al., Interleukin-6- and cyclic AMP -mediated signaling potentiates neuroendocrine...intracellular cyclic AMP . Proc Natl Acad Sci U S A, 1994. 91(12): p. 5330-4. 25. Amorino, G.P. and S.J. Parsons, Neuroendocrine cells in prostate cancer...Aggarwal S, Kim SW, Ryu SH, Chung WC and Koo JS. Growth suppression of lung cancer cells by targeting cyclic AMP response ele- ment-binding protein

  9. Neuro-endocrine tumours of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Soussi, A.C.; Benghiat, A.; Holgate, C.S.; Majumdar, B. (Derbyshire Royal Infirmary, Derby (UK))

    1990-06-01

    The authors report on two types of neuroendocrine carcinoma of the heat and neck, small cell carcinoma of the ethmoid and large cell carcinoma of the larynx, demonstrating a differential response to radiotherapy. (author).

  10. Phthalates Deregulate Cell Proliferation, but Not Neuroendocrine Transdifferentiation, in Human LNCaP Prostate Cancer Cell Model

    Czech Academy of Sciences Publication Activity Database

    Hrubá, Eva; Pernicová, Zuzana; Palková, L.; Souček, Karel; Vondráček, Jan; Machala, M.

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 56-61 ISSN 0015-5500 R&D Projects: GA MŠk(CZ) EE2.3.30.0030; GA MŠk(CZ) ED1.100/02/0123 Institutional support: RVO:68081707 Keywords : phthalates * prostate cancer cells * cell cycle modulation Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

  11. [Laryngeal neuroendocrine carcinoma: a case report].

    Science.gov (United States)

    Hallaoui, Y; El Kohen, A; Sefiani, S; Benchekroun, L; Jazouli, N; Kzadri, M

    2004-01-01

    Laryngeal neuroendocrine carcinomas are uncommon and not well known tumors. Three histological subtypes, each of them with a different prognosis and treatment, can be identified. We report a case of a large cell laryngeal neuroendocrine carcinoma in 32 old-year boy who presented a right glotto-subglottic tumoral process. The patient was treated by total laryngectomy associated with bilateral functional neck dissection but without postoperative chemotherapy. A disease recurrence occured three months after surgery consisting on a massive involvment of laterocervical and sus clavicular lymph nodes. The authors discussed the clinical features, the histological and immunohistochemical characteristics, the treatment and the prognosis of laryngeal neuroendocrine carcinoma, according to literature. (full article translated in English available on www.ent-review.com).

  12. Targeting Neuroendocrine Differentiation for Prostate Cancer Radiosensitization

    Science.gov (United States)

    2014-10-01

    doses when ACREB was expressed (Fig. 6A). Because clonogenic assay assesses the reproductive ability of cells after a single exposure, which is...29] Slovin SF. Neuroendocrine differentiation in prostate cancer: a sheep in wolf’s clothing? Nat Clin Pract Urol. 2006;3:138-144. [30] Lilleby W

  13. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    Pavel M.E., Baum U., Hahn E.G., Hensen J. Doxorubucin and streptozocin after failed biotherapy of Neuroendocrine tumors. Int J. Gastrointest Cancer 2005; 35 179-185. 33. Yao J.C., Phan A., Hoff P.M., et al. Targeting vas- cular endothelial growth factor in advanced carci- noid tumors: a random assignment phase II study.

  14. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  15. Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature

    Directory of Open Access Journals (Sweden)

    Antonio D'Antonio

    2016-02-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT scan of pelvis showed an enlarged uterus (20,0 × 12,0 cm with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option.

  16. EGF Prevents the Neuroendocrine Differentiation of LNCaP Cells Induced By Serum Deprivation: The Modulator Role of P13K/Akt

    Directory of Open Access Journals (Sweden)

    Rosa M. Martín-Orozco

    2007-08-01

    Full Text Available The primary focus of this investigation was to study the relationship between neuroendocrine (NE differentiation, epidermal growth factor (EGF because both have been implicated in the progression of prostate cancer. For this purpose, we used gefitinib, trastuzumab, which are inhibitors of EGF receptor (EGFR, ErbB2, respectively. EGF prevents NE differentiation induced by androgen depletion. This effect is prevented by gefitinib, which blocks the activation of EGFR, ErbB2, stimulation of mitogen-activated protein kinase (MAPK, cell proliferation induced by EGF. Conversely, trastuzumab does not inhibit the effect of EGF on EGFR phosphorylation, MAPK activity, cell proliferation, NE differentiation, although it reduces ErbB2 levels specifically, suggesting that ErbB2 is not necessary to inhibit NE differentiation. Prevention of NE differentiation by EGF is mediated by a MAPK-dependent mechanism, requires constitutive Akt activation. The abrogation of the PI3K/Akt pathway changes the role of EGF from inhibitor to inductor of NE differentiation. We show that EGFR tyrosine kinase, MAPK, PI3K inhibitors inhibit the cell proliferation stimulated by EGF but induce the acquisition of NE phenotype. Altogether, the present data should be borne in mind when designing new clinical schedules for the treatment of prostate cancer, including the use of ErbB receptors, associated signaling pathway inhibitors.

  17. The neuropeptide schistosomin and haemolymph from parasitized snails induce similar changes in excitability in neuroendocrine cells controlling reproduction and growth in a freshwater snail

    NARCIS (Netherlands)

    Hordijk, P. L.; de Jong-Brink, M.; ter Maat, A.; Pieneman, A. W.; Lodder, J. C.; Kits, K. S.

    1992-01-01

    Infection of the snail Lymnaea stagnalis with the schistosome parasite Trichobilharzia ocellata results in inhibition of reproduction and in giant growth. Parasite-related effects on the neuroendocrine centres that control these processes were studied electrophysiologically. Haemolymph from infected

  18. Perinatal exposure to organohalogen pollutants decreases vasopressin content and its mRNA expression in magnocellular neuroendocrine cells activated by osmotic stress in adult rats

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported t...

  19. Development of the Neuroendocrine Hypothalamus.

    Science.gov (United States)

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-03-15

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. Copyright © 2016 John Wiley & Sons, Inc.

  20. Radiology of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hako, R.; Hakova, H.; Gulova, I.

    2011-01-01

    Neuroendocrine tumors arise in the bronchopulmonary or gastrointestinal tract, but they can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Most NETs have nonspecific imaging characteristics. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging should involve multi-phase computed tomography, contrast material-enhanced magnetic resonance imaging, contrast-enhanced ultrasonography and other one. Hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Transcatheter arterial embolization may be used alone or in combination with chemo embolization. Ablative techniques, hepatic cryotherapy and percutaneous ethanol injection may then be undertaken. A multidisciplinary approach to treatment and follow-up is important. (author)

  1. Immunohistochemical study of pancreatic neuroendocrine tumor in Panthera tigris tigris.

    Science.gov (United States)

    Nyska, A; Goldstein, J; Eshkar, G; Klein, B

    1996-07-01

    The histological and immunohistochemical characteristics of a case of pancreatic neuroendocrine tumor are described in a 14-yr-old female Bengal tiger (Panthera tigris tigris) housed at the New Biblical Zoo of Jerusalem, Jerusalem, Israel, 1994. The neoplastic cells were immunohistochemically negative for insulin and glucagon, slightly positive for neuron-specific enolase, moderately positive for serotonin and somatostatin, and markedly positive for chromogranine A and gastrin. This is the first documentation of a pancreatic neuroendocrine tumor in the tiger.

  2. Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor

    Directory of Open Access Journals (Sweden)

    Natsuko Makihara

    2012-06-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

  3. Radionuclide Therapy for Neuroendocrine Tumors.

    Science.gov (United States)

    Cives, Mauro; Strosberg, Jonathan

    2017-02-01

    Peptide receptor radionuclide therapy (PRRT) is a form of systemic radiotherapy that allows targeted delivery of radionuclides to tumor cells expressing high levels of somatostatin receptors. The two radiopeptides most commonly used for PRRT, 90 Y-DOTATOC and 177 Lu-DOTATATE, have been successfully employed for more than a decade for the treatment of advanced neuroendocrine tumors (NETs). Recently, the phase III, randomized NETTER-1 trial has compared 177 Lu-DOTATATE versus high-dose octreotide LAR in patients with progressive, metastatic midgut NETs, demonstrating exceptional tolerability and efficacy. This review summarizes recent developments in the field of radionuclide therapy for gastroenteropancreatic and lung NETs and considers possible strategies to further enhance its clinical efficacy.

  4. Chronic effects of neuroendocrine regulatory peptide (NERP-1 and -2) on insulin secretion and gene expression in pancreatic β-cells.

    Science.gov (United States)

    Kim, Ji-Won; Rhee, Marie; Park, Jae-Hyung; Yamaguchi, Hideki; Sasaki, Kazuki; Minamino, Naoto; Nakazato, Masamitsu; Song, Dae-Kyu; Yoon, Kun-Ho

    2015-02-06

    Neuroendocrine regulatory peptides (NERP-1 and -2) are novel amidated peptides derived from VGF, a polypeptide secreted from neurons and endocrine cells through a regulated pathway. Dr. Nakazato Masamitsu reported that NERP-1 and -2 may have a local modulator function on the human endocrine system, and clearly showed expression of NERP-1 and -2 in human pancreas islets. Based on these data, we investigated the alteration of insulin secretion, insulin granule-related protein, and pancreas-specific transcription factors in response to NERPs expression. We confirmed the expression of NERP-1 and -2 in the pancreas of a human diabetes patient, in addition to diabetic animal models. When INS1 cells and primary rat islets were incubated with 10nM NERPs for 3 days, glucose-stimulated insulin secretion levels were blunted by NERP-1 and -2. The number of insulin granules released from the readily releasable pool, which is associated with the first phase of glucose-stimulated insulin release, was decreased by NERP-1 and -2. Insulin granule-related proteins and mRNAs were down-regulated by NERP-2 treatment. NERP-2 decreased the expression of BETA2/NeuroD and insulin and controlled the nucleo-cytoplasmic translocation of FOXO1 and Pdx-1. We observed that NERP-2 levels were dramatically increased in diabetic pancreas. In conclusion, NERP-2 may play an important role in insulin secretion through the regulation of insulin secretory granules and β-cell transcription factors. In addition, NERP-2 expression is increased in diabetic conditions. Therefore, we suggest that NERPs may be potent endogenous suppressors of glucose-dependent insulin secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity

    Science.gov (United States)

    Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

    2013-01-01

    For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of “neuroendocrine self-peptides” has been proposed, together with the definition of “neuroendocrine self.” Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic

  6. Primary giant hepatic neuroendocrine carcinoma: a case report.

    Science.gov (United States)

    Rocca, Aldo; Calise, Fulvio; Marino, Giuseppina; Montagnani, Stefania; Cinelli, Mariapia; Amato, Bruno; Guerra, Germano

    2014-01-01

    Carcinoid tumours arise from neuroendocrine cells and may develop in almost any organ. These type of tumours actually are correctly termed neuroendocrine tumours. Hepatic neuroendocrine carcinomas rarely arise as primary tumour; in fact on 100 cases reported in literature just a few of these are of primary nature. We report the case of a giant hepatic neuroendocrine carcinoma in a 55-year-old man. The symptoms were only recurrent hypoglycemia and an abdominal mass. Diagnosis was performed by blood analysis, ultrasonography, TC scan and In111-DTPA-octreotide scan. Surgical treatment occurred by an en bloc removal of the mass and a wide resection with free margins. Histological examination confirmed diagnosis. Clinical and instrumental diagnostic follow-up show the patient still alive, in very good conditions and disease free two years after surgery. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Neuroendocrine carcinoma of the prostate gland.

    Science.gov (United States)

    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas; Mora, Adam

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease.

  8. Mediastinal Teratoma with Neuroendocrine Features in 34-Year-Old Male with Syncope

    Directory of Open Access Journals (Sweden)

    Peter A. Andrawes

    2015-01-01

    Full Text Available Neuroendocrine tumors that arise in an extragonadal teratoma are extremely rare. Somatic-type malignancy, defined as any sarcoma, carcinoma, leukemia, or lymphoma developing in a germ cell tumor, occurs in approximately 2% of all germ cell tumors. Our case represents a mediastinal mass that was incidentally found in a patient with syncope. Surgical resection confirmed mature teratoma with neuroendocrine features.

  9. Neuroendocrine Carcinoma: Immunohistochemistry Department Of Cancer Institute 1996 - 2000

    Directory of Open Access Journals (Sweden)

    Yazdani F

    2003-07-01

    Full Text Available Dispersed neuroendocrine system (D.N.S consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:"nMaterials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute."nResults: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent. The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen."nConclusion: Immunohistochemically N.S.E (Neuron Specific Enolase show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A."n(Epithelial Membrane Antigen were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and

  10. Segregation of neuronal and neuroendocrine differentiation in the sympathoadrenal lineage.

    Science.gov (United States)

    Huber, Katrin

    2015-01-01

    Neuronal and neuroendocrine cells possess the capacity for Ca(2+)-regulated discharge of messenger molecules, which they release into synapses or the blood stream, respectively. The neural-crest-derived sympathoadrenal lineage gives rise to the sympathetic neurons of the autonomic nervous system and the neuroendocrine chromaffin cells of the adrenal medulla. These cells provide an excellent model system for studying common and distinct developmental mechanisms underlying the acquisition of neuroendocrine and neuronal properties. As catecholaminergic cells, they possess common markers related to noradrenaline synthesis, storage and release, but they also display diverging gene expression patterns and are morphologically and functionally different. The precise mechanisms that underlie the diversification of sympathoadrenal cells into neurons and neuroendocrine cells are not fully understood. However, in the past we could show that the establishment of a chromaffin phenotype does not depend on signals from the adrenal cortex and that chromaffin cells and sympathetic neurons apparently differ from the onset of their catecholaminergic differentiation. Nevertheless, the cues that specifically induce neuroendocrine features remain elusive. The early development of the progenitors of chromaffin cells and sympathetic neurons depends on a common set of transcription factors with overlapping but distinct influences on their development. In addition to the well-defined role of transcription factors as developmental regulators, our understanding of post-transcriptional gene regulation by microRNAs has substantially increased within the last few decades. This review highlights the major similarities and differences between chromaffin cells and sympathetic neurons, summarizes our current knowledge of the roles of selected transcription factors, microRNAs and environmental signals for the neuroendocrine differentiation of sympathoadrenal cells, and draws comparisons with the

  11. Role of High-Resolution Chest Computed Tomography in a Child with Persistent Tachypnoea and Intercostal Retractions: A Case Report of Neuroendocrine Cell Hyperplasia

    Science.gov (United States)

    Lelii, Mara; Patria, Maria Francesca; Pinzani, Raffaella; Tenconi, Rossana; Mori, Alessandro; Bonelli, Nicola; Principi, Nicola

    2017-01-01

    Background: Chronic interstitial lung diseases in children (chILD) are a heterogeneous group of disorders that can represent a clinical challenge for pediatric pneumologists. Among them, neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease prevalent in the first years of life that spontaneously improves over time. The clinical presentation of NEHI is indistinguishable from other interstitial lung diseases, so a correct and non-invasive diagnosis by chest computed tomography (CT) without lung biopsy might not be simple. Case presentation: An 8-month-old male infant presented with a history of chronic tachypnoea and dyspnoea since 6 months of age. The patient was born at term, with APGAR scores of 9 and 10 at 1 and 5 min, respectively. Since his second month of life, the patient suffered from abnormal breathing, which was characterized by mild tachypnoea and costal retractions that worsened during breastfeeding, crying, and respiratory infections. Bilateral inspiratory crackles, preferential to the lung bases, without oxygen desaturation were detected. A chest X-ray showed a diffuse over-inflation of the lungs, but laboratory tests did not reveal any abnormalities. High-resolution chest CT documented patchy areas of ground-glass opacity involving the right upper lobe, middle lobe, and lingula, and showed mosaic areas of air-trapping, suggesting a diagnosis of NEHI. The infant was discharged without therapy and gradually improved over time. At 1 year of age, the patient was eupnoeic and chest auscultation had normalized. Conclusions: NEHI is an interstitial disease of infancy characterized by tachypnoea from the first months of life, with a good prognosis and for which a rational diagnostic approach is crucial for making a specific, early diagnosis. Initially, clinical suspicions can be confirmed with reasonable accuracy by a CT scan of the chest. Other more invasive and more expensive investigations should be reserved for selected cases that do

  12. Gastroenteropancreatic neuroendocrine tumors (GEP-NETS)

    International Nuclear Information System (INIS)

    Vargas Martinez, Cristian Camilo; Castano Llano, Rodrigo

    2010-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are rare neoplasms which can occur anywhere in the gastrointestinal tract. Their particular characteristics include uptake of silver salts, neuroendocrine cell marker expression and hormonal secretory granules. Depending on their size, anatomical location and upon whether or not metastasis has occurred, these tumors can show different clinical patterns and have different prognoses. Early diagnosis is essential for treating these lesions and improving the patients' prognoses, but it requires a high degree of suspicion and confirmation by special testing. Surgical treatment is the first choice, but other medical therapy can be helpful for patients who have unresectable disease. This review presents the most relevant aspects of classification, morphology, methods of locating tumors, diagnosis and treatment of GEP-NETS. It presents only the Colombian experience in the epidemiology and management of these tumors.

  13. Neuroendocrine Carcinomas of the Gastroenteropancreatic System

    DEFF Research Database (Denmark)

    Ilett, Emma Elizabeth; Langer, Seppo W; Olsen, Ingrid Holst

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type....... Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4-16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning...... detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation...

  14. Molecular basis for vulnerability to mitochondrial and oxidative stress in a neuroendocrine CRI-G1 cell line.

    Directory of Open Access Journals (Sweden)

    Natasha Chandiramani

    2011-01-01

    Full Text Available Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types.Starting with an insulinoma cell line as a model for a neuronal/endocrine cell type, we isolated a novel subclonal line (named CRI-G1-RS that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors than the parental CRI-G1 line (renamed CRI-G1-RR for clarity. Compared to parental RR cells, RS cells were also more vulnerable to direct oxidative stress, but equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition-induced apoptosis. Thus, differential vulnerability to mitochondrial toxins between these two cell types likely reflects differences in their ability to handle metabolically generated reactive oxygen species rather than differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1 inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2 decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3 increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; (4 increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate; and (5 reconstitution of glucose-stimulated insulin secretion.The molecular profile presented here will enable identification of individual genes or gene clusters that shape vulnerability to mitochondrial dysfunction and

  15. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    Science.gov (United States)

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies.

  16. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl; Wolstenholme, Jennifer; Trudeau, Vance L

    2014-07-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  17. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  18. Interplay of CREB and ATF2 in Ionizing Radiation-Induced Neuroendocrine Differentiation of Prostate Cancer Cells

    Science.gov (United States)

    2012-06-01

    AND SALIVARY GLANDS TELL US ABOUT THE OXIDATIVE STRESS STATUS OF THE PROSTATE? A PRECLINICAL STEP TOWARDS INDIVIDUALIZATION OF PROSTATE CANCER ...eugonadal). Serum testosterone levels were determined after 72hrs and the prostate, salivary glands and dermal papillary cells (DPC) of the hair...were no inter-individual differences between the OS status of the prostate, salivary glands and DPC (p0.01). CONCLUSIONS: The intensity of prostatic

  19. Neuroendocrine targets of endocrine disruptors.

    Science.gov (United States)

    Gore, Andrea C

    2010-01-01

    The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions.

  20. Mixed acinar-neuroendocrine carcinoma of the pancreas

    DEFF Research Database (Denmark)

    Jakobsen, Mark; Klöppel, Günter; Detlefsen, Sönke

    2016-01-01

    cells in the cystic areas were reminiscent of acinar cells, and the majority was arranged in a solid growth pattern. Immunohistochemistry revealed >30% positivity for chymotrypsin, chromogranin A, synaptophysin, and CD56. The diagnosis of a mixed acinar-neuroendocrine carcinoma (MAEC) was made. Review...

  1. Neuroendocrine immunoregulation in multiple sclerosis.

    Science.gov (United States)

    Deckx, Nathalie; Lee, Wai-Ping; Berneman, Zwi N; Cools, Nathalie

    2013-01-01

    Currently, it is generally accepted that multiple sclerosis (MS) is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  2. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  3. Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

    Science.gov (United States)

    Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Bartho, Julia; Blois, Sandra M; Karpf, Eva F; Sedlmayr, Peter; Klapp, Burghard F; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C

    2010-03-01

    Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH

  4. Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

    Science.gov (United States)

    2015-10-15

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Multiple Endocrine Neoplasia Type 1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor

  5. Minireview: Role of glia in neuroendocrine function.

    Science.gov (United States)

    Garcia-Segura, Luis M; McCarthy, Margaret M

    2004-03-01

    Long relegated to the backwaters of neuroendocrinology, it is becoming increasingly apparent that glial cells of the central and peripheral nervous system are key participants because they are capable of both sending and receiving hormonal signals. Hormones are also a critical component of neuronal/glial cross talk, leading to neuromodulatory and neurotrophic actions under physiological and pathological conditions. In the peripheral nervous system, hormonal actions on Schwann cells and hormonal metabolites produced by these glial cells promote myelin formation and the remyelination and regeneration of injured nerves. In the central nervous system, glial cells participate in the hormonal regulation of synaptic function, synaptic plasticity, myelin formation, cognition, sleep, and the response of nervous tissue to injury. In addition, central glial cells participate in the regulation of hormonal secretion by hypothalamic neurons. Therefore, glial cells are a key element to understanding hormonal actions in the nervous system and the regulation of neuroendocrine events.

  6. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  7. Dermatomyositis Associated with Lung Neuroendocrine Carcinoma

    Science.gov (United States)

    Takashima, Reina; Takamatsu, Kazufumi; Shinkawa, Yutaka; Yagita, Masato; Fukui, Motonari; Fujita, Masaaki

    2017-01-01

    Dermatomyositis is associated with various types of malignancy. However, the association of dermatomyositis with lung neuroendocrine carcinoma is rare. We herein report a case of dermatomyositis with lung neuroendocrine carcinoma. PMID:28321077

  8. Dermatomyositis Associated with Lung Neuroendocrine Carcinoma

    OpenAIRE

    Takashima, Reina; Takamatsu, Kazufumi; Shinkawa, Yutaka; Yagita, Masato; Fukui, Motonari; Fujita, Masaaki

    2017-01-01

    Dermatomyositis is associated with various types of malignancy. However, the association of dermatomyositis with lung neuroendocrine carcinoma is rare. We herein report a case of dermatomyositis with lung neuroendocrine carcinoma.

  9. Neuroendocrine-immune interactions and responses to exercise.

    Science.gov (United States)

    Fragala, Maren S; Kraemer, William J; Denegar, Craig R; Maresh, Carl M; Mastro, Andrea M; Volek, Jeff S

    2011-08-01

    This article reviews the interaction between the neuroendocrine and immune systems in response to exercise stress, considering gender differences. The body's response to exercise stress is a system-wide effort coordinated by the integration between the immune and the neuroendocrine systems. Although considered distinct systems, increasing evidence supports the close communication between them. Like any stressor, the body's response to exercise triggers a systematic series of neuroendocrine and immune events directed at bringing the system back to a state of homeostasis. Physical exercise presents a unique physiological stress where the neuroendocrine and immune systems contribute to accommodating the increase in physiological demands. These systems of the body also adapt to chronic overload, or exercise training. Such adaptations alleviate the magnitude of subsequent stress or minimize the exercise challenge to within homeostatic limits. This adaptive capacity of collaborating systems resembles the acquired, or adaptive, branch of the immune system, characterized by the memory capacity of the cells involved. Specific to the adaptive immune response, once a specific antigen is encountered, memory cells, or lymphocytes, mount a response that reduces the magnitude of the immune response to subsequent encounters of the same stress. In each case, the endocrine response to physical exercise and the adaptive branch of the immune system share the ability to adapt to a stressful encounter. Moreover, each of these systemic responses to stress is influenced by gender. In both the neuroendocrine responses to exercise and the adaptive (B lymphocyte) immune response, gender differences have been attributed to the 'protective' effects of estrogens. Thus, this review will create a paradigm to explain the neuroendocrine communication with leukocytes during exercise by reviewing (i) endocrine and immune interactions; (ii) endocrine and immune systems response to physiological stress

  10. Imaging and Therapy of Neuroendocrine Tumors with Radiolabeled Somatostatin Analogs

    NARCIS (Netherlands)

    T. Brabander (Tessa)

    2017-01-01

    markdownabstractNeuroendocrine tumors are a heterogeneous group of tumors, but they generally express a high number of somatostatin receptors on their cell membranes. This receptor is a target for somatostatin analogs, which can be labeled with radionuclides for both imaging and therapy. In this

  11. Expression and Clinicopathologic Significance of Human Achaete-scute Homolog 1 in Pulmonary Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Donghan ZHENG

    2010-04-01

    Full Text Available Background and objective Human achaete-scute homolog 1 (hASH1 gene plays a critical role in development of the central nervous system, automatic nervous system, adrenal medullary chromaffin cells, thyroid C cells and pulmonary neuroendocrine cells. The aim of this study is to determine hASH1 gene expression in the normal lung tissue and various types of lung tumors, to analyze whether its expression correlated with pulmonary neuroendocrine markers, and to explore the possibility of hASH1 as clinical pathological markers in the neuroendocrine tumors compared with previous neuroendocrine tumor markers. Methods hASH1, Chromogranin A, Synaptophysin and CD56 expression were examined in lung tumor specimens (lung inflammatory pseudotumor, squamous cell carcinoma, adenocarcinomas, large cell carcinoma, typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas and small cell lung carcinoma and corresponding normal lung specimens using immunohistochemistry (S-P method. Western blot and reverse transcription polymerase chain reaction (RT-PCR assay were applied to detect the expressions of hASH1 protein and mRNA in lung cancer tissues. Results hASH1 expression was positive in 2/16 (12.5% typical carcinoids, 15/20 (75% atypical carcinoids, 6/10 (60% large cell neuroendocrine carcinomas and 31/40 (77.5% small cell lung carcinoma, respectively, but not in any normal lung tissue (0/10, lung inflammatory pseudotumor (0/49, squamous cell carcinoma (0/30, adenocarcinomas (0/30 or large cell carcinoma (0/20. There was a significant difference in hASH1 expression between typical carcinoids and atypical carcinoids (P 0.05. hASH1 expression highly closely correlated with Chromogranin A, Synaptophysin and CD56 expression (P < 0.05. Conclusion hASH1 is a new kind of highly specific markers of pulmonary neuroendocrine tumours, and may be applied to clinical pathology diagnosis of the pulmonary neuroendocrine tumors.

  12. Neuroendocrine tumors and fibrosis: An unsolved mystery?

    Science.gov (United States)

    Laskaratos, Faidon-Marios; Rombouts, Krista; Caplin, Martyn; Toumpanakis, Christos; Thirlwell, Christina; Mandair, Dalvinder

    2017-12-15

    Neuroendocrine tumors are a heterogeneous group of slow-growing neoplasms arising mainly from the enterochromaffin cells of the digestive and respiratory tract. Although they are relatively rare, their incidence is rising. It has long been observed that they often are associated with the development of fibrosis, both local and distant. Fibrotic complications, such as carcinoid heart disease and mesenteric desmoplasia, may lead to considerable morbidity or even affect prognosis. The elucidation of the pathophysiology of fibrosis would be of critical importance for the development of targeted therapeutic strategies. In this article, the authors review the available evidence regarding the biological basis of fibrosis in neuroendocrine tumors. They explore the role of the tumor microenvironment and the interplay between tumor cells and fibroblasts as a key factor in fibrogenesis and tumor development/progression. They also review the role of serotonin, growth factors, and other peptides in the development of carcinoid-related fibrotic reactions. Cancer 2017;123:4770-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Immunohistochemical identification of neuron-specific enolase, synaptophysin, chromogranin and endocrine granule constituent in neuroendocrine tumours

    DEFF Research Database (Denmark)

    Vyberg, M; Horn, T; Francis, D

    1990-01-01

    Immunohistochemical identification of neuroendocrine tumour markers in paraffin embedded material from 22 tumours (5 small cell carcinomas of the lung (SCCL), 12 carcinoids, 2 medullary thyroid carcinomas, 2 pheochromocytomas and one paraganglioma) with electron microscopically verified dense...

  14. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...

  15. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment. Copyright © 2012 S. Karger AG, Basel.

  16. Electroconvulsive therapy's mechanism of action: neuroendocrine hypotheses.

    Science.gov (United States)

    Haskett, Roger F

    2014-06-01

    Despite a range of etiological theories since the introduction of electroconvulsive therapy (ECT) more than 75 years ago, its mechanism of action remains poorly understood. The neuroendocrine hypothesis is based on the seizure-related release of hypothalamic hormones into the blood and cerebrospinal fluid and evidence of endocrine dysfunction in many patients with severe mood disorder. The specific effect of ECT was hypothesized to result from the transverse passage of current through the brain with direct stimulation of axial structures including the diencephalon. The prompt release of adrenocorticotropic hormone, cortisol, and prolactin into blood followed ECT with a return to pretreatment baseline levels in several hours. The elevated levels of hormones were absorbed by the cerebrospinal fluid, providing contact with brain cells and central nervous system structures. An apparently specific pattern of ECT-induced hormone changes, limited to prolactin and cortisol, suggested that ECT released a substance with dopaminergic antagonist and antipsychotic properties. As hypothalamic dysfunction is a key finding in endogenomorphic depression and the abnormal endocrine and physiological functions usually normalize with recovery, this led to a search for biological markers that would supplement clinical assessment of diagnosis and treatment response. One of these, the overnight dexamethasone suppression test found that 40% to 50% of melancholic depressed patients had abnormal results, whereas 90% of control patients suppressed normally. This was followed by a period of uncritical overenthusiasm followed by wholesale rejection of the clinical neuroendocrine strategies. Several key methodological issues received inadequate attention, and there have been calls to revisit this topic.

  17. Neuroendocrine carcinoma of the mammary gland in a dog.

    Science.gov (United States)

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations.

    Directory of Open Access Journals (Sweden)

    Nicola Fusco

    Full Text Available Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

  19. A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland.

    Science.gov (United States)

    Kasajima, Atsuko; Cameselle-Teijeiro, José; Loidi, Lourdes; Takahashi, Yoshio; Nakashima, Noriaki; Sato, Satoko; Fujishima, Fumiyoshi; Watanabe, Mika; Nakazawa, Tadao; Naganuma, Hiroshi; Kondo, Tetsuo; Kato, Ryohei; Sasano, Hironobu

    2016-12-01

    Neuroendocrine tumors of the thyroid gland are generally considered to derive from parafollicular endocrine cells (C cells) and are generally referred to as medullary thyroid carcinomas (MTC). Calcitonin secretion is almost always detected in MTC and a prerequisite for both clinical and pathological diagnosis. Thyroid neuroendocrine tumors without any apparent calcitonin secretion reflect a diagnostic dilemma because non-calcitonin-producing MTCs have virtually not been characterized. Here, we report a case of primary thyroid neuroendocrine tumors lacking calcitonin secretion or expression. The tumor cells expressed cytokeratins, chromogranin A, and synaptophysin, all of which were consistent with epithelial and neuroendocrine differentiation. Thyroid transcription factor-1 paired box gene 8, and carcinoembryonic antigen were also immunohistochemically detected, consistent with its thyroid origin. However, the tumor was negative for calcitonin both by immunohistochemistry and in situ hybridization, hence, not meeting the definition of MTC. Despite the loss of calcitonin expression, immunoreactivity for the calcitonin-gene-related peptide was detected in the tumor. Somatic gene mutations of RET, H-RAS, K-RAS, or BRAF were not detected in this case. A limited number of calcitonin non-producing thyroid neuroendocrine tumors are available in the scientific literature available in English, and its etiology and clinical manifestations remain largely unknown. Our case, along with the rare, previously reported cases, suggests that calcitonin non-producing neuroendocrine tumors of the thyroid gland are most likely derived from C cells, but should be differentiated from ordinary MTCs.

  20. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  1. Quantitative proteomics in teleost fish: Insights and challenges for neuroendocrine and neurotoxicology research

    OpenAIRE

    Martyniuk, Christopher J.; Popesku, Jason T.; Chown, Brittany; Denslow, Nancy D.; Trudeau, Vance L.

    2011-01-01

    Neuroendocrine systems integrate both extrinsic and intrinsic signals to regulate virtually all aspects of an animal’s physiology. In aquatic toxicology, studies have shown that pollutants are capable of disrupting the neuroendocrine system of teleost fish, and many chemicals found in the environment can also have a neurotoxic mode of action. Omics approaches are now used to better understand cell signaling cascades underlying fish neurophysiology and the control of pituitary hormone release,...

  2. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1–7 Cells for Evaluation of the Neuroendocrine Effects of Essential Oils

    Directory of Open Access Journals (Sweden)

    Dai Mizuno

    2015-01-01

    Full Text Available Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer’s disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells. In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2, aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen. Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils.

  3. Radiosensitivity related to neuroendocrine and endodermal differentation in lung carcinoma lines

    International Nuclear Information System (INIS)

    Duchesne, G.; Casoni, A.; Pera, M.

    1988-01-01

    A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. 30 refs.; 3 figs.; 3 tabs

  4. A Neuroendocrine Carcinoma of Undetermined Origin in a Dog

    OpenAIRE

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-01-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-l...

  5. A neuroendocrine carcinoma of undetermined origin in a dog.

    Science.gov (United States)

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-09-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.

  6. Neuroendocrine regulation of lactation and milk production.

    Science.gov (United States)

    Crowley, William R

    2015-01-01

    Prolactin (PRL) released from lactotrophs of the anterior pituitary gland in response to the suckling by the offspring is the major hormonal signal responsible for stimulation of milk synthesis in the mammary glands. PRL secretion is under chronic inhibition exerted by dopamine (DA), which is released from neurons of the arcuate nucleus of the hypothalamus into the hypophyseal portal vasculature. Suckling by the young activates ascending systems that decrease the release of DA from this system, resulting in enhanced responsiveness to one or more PRL-releasing hormones, such as thyrotropin-releasing hormone. The neuropeptide oxytocin (OT), synthesized in magnocellular neurons of the hypothalamic supraoptic, paraventricular, and several accessory nuclei, is responsible for contracting the myoepithelial cells of the mammary gland to produce milk ejection. Electrophysiological recordings demonstrate that shortly before each milk ejection, the entire neurosecretory OT population fires a synchronized burst of action potentials (the milk ejection burst), resulting in release of OT from nerve terminals in the neurohypophysis. Both of these neuroendocrine systems undergo alterations in late gestation that prepare them for the secretory demands of lactation, and that reduce their responsiveness to stimuli other than suckling, especially physical stressors. The demands of milk synthesis and release produce a condition of negative energy balance in the suckled mother, and, in laboratory rodents, are accompanied by a dramatic hyperphagia. The reduction in secretion of the adipocyte hormone, leptin, a hallmark of negative energy balance, may be an important endocrine signal to hypothalamic systems that integrate lactation-associated food intake with neuroendocrine systems. © 2015 American Physiological Society.

  7. Nuclear medicine applications for neuroendocrine tumors.

    Science.gov (United States)

    Chatal, J F; Le Bodic, M F; Kraeber-Bodéré, F; Rousseau, C; Resche, I

    2000-11-01

    Sensitive, specific radiopharmaceuticals are available for scintigraphic diagnosis and internal radiotherapy of neuroendocrine tumors. (123)I-MIBG (metaiodobenzylguanidine) scintigraphy is the examination of choice for visualizing tumor sites of pheochromocytoma. In the event of malignant pheochromocytoma or carcinoid tumor, this examination allows assessment of the presence or absence of tumor uptake and can guide radiotherapy with (131)I-MIBG. The peptides secreted by neuroendocrine tumors can be radiolabeled for targeting of their specific receptors. Scintigraphy using a (111)In-labeled somatostatin analog (octreotide) is the examination of choice for diagnosis of the spread of gastroenteropancreatic and carcinoid tumors, as it is more sensitive than morphologic imaging techniques. It can also guide radiotherapy performed with the same pharmaceutical vector. These same two agents (MIBG and octreotide) can be used therapeutically by replacing (123)I with (131)I and (111)In by (90)Y. A transient palliative effect is obtained for a variable number of tumors (most often large ones) that take up the radiopharmaceutic agent well. There is general consensus that, for relatively radioresistant solid tumors, this type of radiotherapy is efficient only in the event of small tumor targets (a few millimeters in diameter) whose uptake is maximal, allowing more homogeneous distribution than that achieved with large tumors. Thus for optimal control of the disease it is recommended first to use scintigraphic imaging to confirm that the tumor takes up the radiopharmaceutical agent in question ((123)I-MIBG or (111)In-octreotide) and then reduce the tumor burden surgically before injecting high therapeutic activity (possibly with reinjection of peripheral stem cells). This treatment can be repeated three times every 3 months before evaluating the response. In these conditions, internal radiotherapy can be beneficial or even determinant for controlling disease progression.

  8. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently.

    Science.gov (United States)

    Hagforsen, Eva; Michaëlsson, Gerd; Stridsberg, Mats

    2010-11-01

    Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors. The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin. Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.

  10. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Science.gov (United States)

    Bertani, Helga; Messerotti, Alessandro; Di Benedetto, Fabrizio; Manta, Raffaele; Greco, Milena; Casoni, Federica; Losi, Luisa; Conigliaro, Rita

    2011-01-01

    Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10%) (1). Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2). Myasthenia gravis (MG) is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR). MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3). No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour. PMID:21603138

  11. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    -lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent arid should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroen-docrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

  12. Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Engelund Luna, Iben; Monrad, Nina; Binderup, Tina

    2016-01-01

    OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological, and bio......OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological...

  13. Primary Neuroendocrine Carcinoma of Ocular Adnexa

    Directory of Open Access Journals (Sweden)

    Daisuke Yamanouchi

    2013-01-01

    Full Text Available We present our findings in a case of primary neuroendocrine carcinoma (NEC of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

  14. The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer

    Science.gov (United States)

    2009-01-01

    for hyaluronic acid and mediates epithelial cell adhesion by its involvement in cell-cell and cell-matrixinteractions [11]. The CD44 isoforms are also...cells in prostate cancer). 2. Invited Speaker, 15th Annual Meeting of the Chinese Urological Society, Kunming, China, September 2008 (Neuroendocrine...School of Medicine to be Professor of Pathology and Director of Urologic Pathology based on experience supported by the award. CONCLUSION

  15. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M.; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E. S.; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M.; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E.; Chisholm, Townley W.; Kim, Seung K.

    2016-01-01

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. PMID:27527793

  16. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research

    Directory of Open Access Journals (Sweden)

    Lutz Kockel

    2016-10-01

    Full Text Available Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals.

  17. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research.

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E S; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E; Chisholm, Townley W; Kim, Seung K

    2016-10-13

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. Copyright © 2016 Kockel et al.

  18. Stimulus-dependent translocation of egg-laying hormone encoding mRNA into the axonal compartment of the neuroendocrine caudodorsal cells

    NARCIS (Netherlands)

    van Minnen, J.; Bergman, J. J.

    2003-01-01

    To get insight into the stimulus-dependent translocation of mRNA encoding neuropeptides to the axonal compartment of neurons, we investigated this process in the egg-laying hormone producing caudodorsal cells of the mollusk Lymnaea stagnalis. The axonal compartment including the nerve terminals of

  19. Stimulus-independent translocation of egg-laying hormone encoding mRNA into the axonal compartment of the neuroendocrine caudodorsal cells

    NARCIS (Netherlands)

    van Minnen, J.; Bergman, J.J.

    2003-01-01

    To get insight into the stimulus-dependent translocation of mRNA encoding neuropeptides to the axonal compartment of neurons, we investigated this process in the egg-laying hormone producing caudodorsal cells of the mollusk Lymnaea stagnalis. The axonal compartment including the nerve terminals of

  20. (CT, MRI, USG) radiological diagnostics of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Cwikla, J.; Furmanek, M.; Walecki, J.; Sankowski, A.; Pawlowska-Detko, A.

    2007-01-01

    Neuroendocrine tumors (NET) consists of a heterogeneneous group of neoplasma, that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, which can be used in the localization and treatment of these tumours. Conventionally NETs may present with a wide variety of functional or nonfuctional endocrinesyndromes and may be familial and have other associated tumors, also they have different histology and prognosis. They originate from endocrine glands such as the pituitary, the parathyroids, and the neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive system (gastroenteropancreatic GEP-NET0 and respiratory tracts. GEp-NET are the the most common including more 70% of all NETs. Imaging modalities and assessment of specific tumors markers offers high sensitivity in establishing the diagnosis and can also have pronostic significance. One of most important single imaging techniques in terms of initial identification and staging o GET-NET are CT and somatostatin receptor scintigraphy (SRS). Other investigation like magnetic resonance imaging (MRI), endoscopic (EUS) are used for the precise localization of GEP-NET. Another techniques including functional approach 123 I MIBG (meta-iodobenzylguanidine scintigraphy) and FDG PET.Important using of imaging approach is monitoring of response on treatment. (author)

  1. Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation.

    Science.gov (United States)

    Jiborn, Thomas; Abrahamson, Magnus; Gadaleanu, Virgil; Lundwall, Ake; Bjartell, Anders

    2006-07-01

    To investigate the expression of cystatin C and the relationship with neuroendocrine differentiation and proliferation in benign and malignant prostatic tissues, as cystatin C, the most important inhibitor of human lysosomal cysteine proteases, is considered to be a major regulator of pathological protein degradation in inflammatory and neoplastic diseases. Immunoreactivity for cystatin C, prostate-specific antigen, Ki-67 and the neuroendocrine marker chromogranin A was examined in whole-mount radical prostatectomy specimens and using tissue microarrays. Cystatin C in tissue homogenates was analysed by Western blotting and enzyme-linked immunosorbent assay (ELISA). The expression and relative levels of cystatin C mRNA were assessed by in situ hybridization and quantitative real-time polymerase chain reaction (QRT-PCR). The intensity of cystatin C immunostaining in Gleason grade 2 and 3 prostate cancer was significantly higher than in benign prostatic tissues, but decreased significantly with increasing Gleason grades. There was strong expression of cystatin C in neuroendocrine-like cells, which increased significantly with increasing Gleason grades. The Ki-67 immunoreactivity also increased significantly during de-differentiation. In situ hybridization showed staining patterns in concordance with the immunohistochemical results. ELISA showed high concentrations of cystatin C in benign and malignant tissue extracts and QRT-PCR further corroborated that the cystatin C gene is highly expressed in both benign and malignant prostatic tissues. There was a significant decrease in the immunohistochemical expression of cystatin C in non-neuroendocrine prostate cancer cells, concomitant with increasing Gleason grades. That there were more strongly cystatin C-positive neuroendocrine-like cells in prostate cancer than in benign prostatic tissue suggests a connection between cystatin C and neuroendocrine differentiation in prostate cancer progression.

  2. Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system

    Directory of Open Access Journals (Sweden)

    Sivero Luigi

    2016-01-01

    Full Text Available The authors evaluated the role of endoscopic techniques in the diagnosis and in the potential treatment of neuroendocrine tumors (NET localized in the gastro-entero-pancreatic system, on the basis of their experience and of the international literature. NET are rare tumors that arise from neuroendocrine cells of the gastrointestinal tract and pancreas. It is a possibility that both the digestive endoscopy and EUS play an important role in the diagnosis, staging and surveillance of this disease. In some cases, especially in the early stages, surgical endoscopy allows the treatment of such tumors.

  3. [Neuroendocrine tumours of the alimentary tract--history and at present].

    Science.gov (United States)

    Mandys, V

    2009-07-01

    Histological classification of the neuroendocrine tumours ("carcinoids") of the alimentary tract, as well as the opinion on biological behaviour of these tumours, changed rapidly within the last decade. Advances in knowledge of cellular biology of the diffuse endocrine system and in clinical diagnostics and treatment of tumours lead to the creation of a new histological classification of neuroendocrine tumours. This classification, apart from essential histological picture and immunohistological characterisation of the markers of neuroendocrine differentiation, also includes definition of biological properties of tumours based on their site of origin, mitotic and proliferative activity of the tumour cells and clinicopathological correlation, including the size of the tumour and its progression. Exact classification of an individual tumour into a corresponding category is an essential condition to select adequate following diagnostic procedures and optimal therapeutic strategy.

  4. Neuroendocrine and Molecular Interactions in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Selma Bozkurt Zincir

    2014-08-01

    Full Text Available There are three basic pillars for the development of eating disorders: genetic predisposition, neuro-endocrine-molecular changes in the brain and metabolic response to it. As a result of neuroendocrine research, a close relationship has been found between neuroendocrine functions and symptom domains of psychiatric disorders such as eating disorders and mood disorders. Certain hormones, neurotransmitters and other molecules which might have effect on the basis of eating disorders can be listed as estrogen, serotonin, leptin, ghreline, alpha-melanocyte stimulating hormone, cholecystokinin, dopamine, noradrenaline, brain-derived neurotropic factor, agouti-related protein, neuropeptide-Y, opioids and their receptors, thiamine, zinc, omega-3 acids. In this review, main neuroendocrine-molecular changes and interactions that occur in the eating disorders have been discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 389-400

  5. Neuroendocrine Disturbances in Huntington's Disease

    Science.gov (United States)

    Saleh, Nadine; Moutereau, Stéphane; Durr, Alexandra; Krystkowiak, Pierre; Azulay, Jean-Philippe; Tranchant, Christine; Broussolle, Emmanuel; Morin, Françoise; Bachoud-Lévi, Anne-Catherine; Maison, Patrick

    2009-01-01

    Background Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized, in addition to neurological impairment, by weight loss suggesting endocrine disturbances. The aims of this study were to look for neuroendocrine disturbances in patients with Huntington's disease (HD) and to determine the relationship with weight loss seen in HD Methods and Finding We compared plasma levels of hormones from the five pituitary axes in 219 patients with genetically documented HD and in 71 sex- and age-matched controls. Relationships between hormone levels and disease severity, including weight-loss severity, were evaluated. Growth hormone (GH) and standard deviation score of insulin-like growth factor 1 (SDS IGF-1) were significantly higher in patients than in controls (0.25 (0.01–5.89) vs. 0.15 (0.005–4.89) ng/ml, p = 0.013 and 0.16±1.02 vs. 0.06±0.91, p = 0.039; respectively). Cortisol was higher (p = 0.002) in patients (399.14±160.5 nmol/L vs. 279.8±130.1 nmol/L), whereas no differences were found for other hormone axes. In patients, elevations in GH and IGF-1 and decreases in thyroid-stimulating hormone, free triiodothyronine and testosterone (in men) were associated with severity of impairments (Independence scale, Functional score, Total Functional Capacity, Total Motor score, Behavioral score). Only GH was independently associated with body mass index (β = −0.26, p = 0.001). Conclusion Our data suggest that the thyrotropic and in men gonadotropic axes are altered in HD according to the severity of the disease. The somatotropic axis is overactive even in patients with early disease, and could be related to the weight loss seen in HD patients. PMID:19319184

  6. DIABETES MELLITUS IN NEUROENDOCRINE DISEASES

    Directory of Open Access Journals (Sweden)

    I. V. Trigolosova

    2014-01-01

    early disability and death of patients with neuroendocrine diseases.

  7. The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning

    Science.gov (United States)

    Conradt, Elisabeth; Hawes, Katheleen; Guerin, Dylan; Armstrong, David A.; Marsit, Carmen J.; Tronick, Edward; Lester, Barry M.

    2016-01-01

    This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of "NR3C1," "11ß-HSD2," and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive…

  8. Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women.

    Science.gov (United States)

    Ronaldson, Amy; Gazali, Ahmad M; Zalli, Argita; Kaiser, Frank; Thompson, Stephen J; Henderson, Brian; Steptoe, Andrew; Carvalho, Livia

    2016-05-01

    The percentage of regulatory T cells (TRegs)-a subtype of T lymphocyte that suppresses the immune response-appears to be reduced in a number of stress-related diseases. The role of the TReg in stress-disease pathways has not yet been investigated. The aim of the study was to investigate the association between biological responsivity to acute psychosocial stress and the percentage of TRegs in healthy older adults. The secondary purpose was to measure the associations between TReg percentage and psychological and physical well-being in the participants. Salivary cortisol and plasma interleukin (IL)-6 samples were obtained from 121 healthy older men and women from the Whitehall II cohort following acute psychophysiological stress testing. Three years later at a follow-up visit, we measured TReg percentages and psychological and physical well-being were recorded using the Short Form 36 Health Survey and the Center for Epidemiologic Studies Depression Scale. Blunted cortisol responses (p = 0.004) and elevated IL-6 responses (p = 0.027) to acute psychophysiological stress were associated with greater TReg percentage independently of age, sex, BMI, smoking status, employment grade, time of testing, and baseline measures of cortisol and IL-6, respectively. Percentage of TRegs was associated cross-sectionally with lower physical (p = 0.043) and mental health status (p = 0.008), and higher levels of depressive symptoms (p = 0.002), independently of covariates. Increased levels of TRegs may act as a defence against increased inflammation and may be a pre-indication for chronically stressed individuals on the cusp of clinical illness.

  9. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

    DEFF Research Database (Denmark)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

    2009-01-01

    in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

  10. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

    Science.gov (United States)

    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  11. The Long Intron 1 of Growth Hormone Gene from Reeves' Turtle (Chinemys reevesii) Correlates with Negatively Regulated GH Expression in Four Cell Lines.

    Science.gov (United States)

    Liu, Wen-Sheng; Ma, Jing-E; Li, Wei-Xia; Zhang, Jin-Ge; Wang, Juan; Nie, Qing-Hua; Qiu, Feng-Fang; Fang, Mei-Xia; Zeng, Fang; Wang, Xing; Lin, Xi-Ran; Zhang, Li; Chen, Shao-Hao; Zhang, Xi-Quan

    2016-04-12

    Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves' turtle (Chinemys reevesii) have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH) cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp), comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS) of the turtle's GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO) cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH) gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves' turtle might correlate with downregulated gene expression.

  12. The Long Intron 1 of Growth Hormone Gene from Reeves’ Turtle (Chinemys reevesii Correlates with Negatively Regulated GH Expression in Four Cell Lines

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Liu

    2016-04-01

    Full Text Available Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves’ turtle (Chinemys reevesii have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp, comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS of the turtle’s GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves’ turtle might correlate with downregulated gene expression.

  13. Peptide receptor therapies in neuroendocrine tumors

    NARCIS (Netherlands)

    Bodei, L.; Ferone, D.; Grana, C. M.; Cremonesi, M.; Signore, A.; Dierckx, R. A.; Paganelli, G.

    Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, able to produce bioactive amines and hormones. NETs tend to be slow growing and are often diagnosed when metastatic. The localization of a NETs and the assessment of the extent of disease are

  14. Molecular neuroendocrine targets for obesity therapy.

    Science.gov (United States)

    de Kloet, Annette D; Woods, Stephen C

    2010-10-01

    Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. During the review period, considerable progress occurred in the understanding of previously described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of the neuroendocrine regulation of energy homeostasis has been expanded. Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical-weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging.

  15. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  16. [Neuroendocrine tumors of the stomach (stomach carcinoid)].

    Science.gov (United States)

    Federmann, M; Bansky, G; Flury, R

    1994-09-27

    We report about two patients with gastric neuroendocrine tumours (carcinoids) and chronic atrophic gastritis. A 68-year-old woman presented with nonspecific dyspeptic complaints. Gastroscopy revealed a single neuroendocrine tumour of the corpus. 33 months after endoscopic therapy she is free of detectable tumour. As cause of an upper gastrointestinal bleeding in a 75-year-old woman, a small ulcerated fundic neuroendocrine tumour was found together with other multiple tumours. Repeated endoscopic removals of these and further developing similar tumours were necessary during a follow-up of 25 months. Neuroendocrine tumours of the stomach are rare and are potentially malignant. According to their clinical context they can be divided into three subtypes: 1. tumours in chronic atrophic gastritis, 2. tumours in multiple endocrine neoplasia type I, 3. sporadic tumours, not associated with particular diseases. The first two types may be gastrin-promoted; they occur often multifocal only in the nonantral mucosa and seem to behave relatively benign. Metastasis limited to regional lymph nodes has not been described often. The very rare third type appears solitary in the whole stomach and seems to have a higher malignant potential with frequent distant metastasis to the liver. Therapy should be mainly guided by subtype and tumour size.

  17. Other PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter; Glaudemans, Andor W J M

    In this article the applicability of (124)I-MIBG and (11)C-5-HTP PET for the detection of abdominal gastro-enteropancreatic neuroendocrine tumors is discussed. (124)I-MIBG is a positron-emitting variant of (123)I-MIBG and therefore suited for PET imaging. Due to the better intrinsic characteristics

  18. Nuclear Medicine Imaging of Neuroendocrine Tumors

    NARCIS (Netherlands)

    Brabander, Tessa; Kwekkeboom, Dik J.; Feelders, Richard A.; Brouwers, Adrienne H.; Teunissen, Jaap J. M.; Papotti, M; DeHerder, WW

    2015-01-01

    An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy

  19. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  20. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  1. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    Pancreatic neuroendocrine tumors (PNET) are increasingly being discovered. A case of PNET diagnosed and treated during the management of acute appendicitis is presented and discussed. The importance of imaging modalities in patients with acute abdominal pain is emphasized. To the best our knowledge, this is the ...

  2. Diagnosis and treatment of bronchopulmonary neuroendocrine tumours

    DEFF Research Database (Denmark)

    Tabaksblat, Elizaveta Mitkina; Langer, Seppo W; Knigge, Ulrich

    2016-01-01

    Bronchopulmonary neuroendocrine tumours (BP-NET) are a heterogeneous population of neoplasms with different pathology, clinical behaviour and prognosis compared to the more common lung cancers. The management of BP-NET patients is largely based on studies with a low level of evidence...

  3. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    preoperative ultrasound examination. Histopathological examination showed only a gangrenous appendix without any neuroendocrine tissue. After the appendectomy, repeat ultrasound and MRI confirmed the presence of a solid pancreatic mass (Fig. 1). Biochemical parameters including tumor markers (24-h urine sample ...

  4. Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review

    Science.gov (United States)

    Ilett, Emma Elizabeth; Langer, Seppo W.; Olsen, Ingrid Holst; Federspiel, Birgitte; Kjær, Andreas; Knigge, Ulrich

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities. PMID:26854147

  5. Breast carcinoma with neuroendocrine features: a brief review

    Directory of Open Access Journals (Sweden)

    Petra Jurčić

    2016-06-01

    Full Text Available Breast carcinoma with neuroendocrine features (BCNF is a rare entity that is defined by a neuroendocrine (NE architecture and cytomorphology combined with an immunohistochemical expression of chromogranin A or B and/or synaptophysin. According to the 2012 World Health Organization (WHO classification, they are classified into three subtypes: invasive breast carcinoma with NE differentiation, well-differentiated NE tumor, and poorly differentiated small cell carcinoma. BCNF are typically positive for the estrogen and progesterone receptor and negative for Her-2/ neu protein. The clinical features are not sufficiently specific to distinguish BCNF from other breast carcinomas. BCNF can mimic benign lesions on mammography, so the additional use of ultrasound or MRI can improve detection. Other imaging tests are useful to detect or rule out metastatic disease. Although standardized treatment guidelines have not yet been established, the mainstay of treatment for early BCNFs is surgery. Adjuvant treatment decisions should be individualized and should take into consideration the prognostic and predictive factors, clinical evidence and the patient’s overall health treatment preferences. Therapeutic options in the metastatic setting include surgery, chemotherapy, peptide receptor radionuclide therapy and molecular-targeted agents. These options are not mutually exclusive and are interchangeable.

  6. Interferon treatment of neuroendocrine tumour xenografts as monitored by MRI

    International Nuclear Information System (INIS)

    Elvin, A.; Oeberg, K.; Lindgren, P.G.; Lundkvist, M.; Wilander, E.; Ericsson, A.; Hemmingsson, A.

    1994-01-01

    The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 nude mice (Balb/c). The purpose of the present study was to establish an animal model that would allow monitoring with magnetic resonance imaging (MRI) of changes induced by interferon (IFN) therapy and to evaluate whether the therapeutic response, as expressed by changes in MR signal characteristics and tumour proliferative activity, could be modulated by different IFN dosages. IFN did not seem to have any obvious antiproliferative effect on the LCC-18 tumour cell line transplanted to nude mice and no convincing treatment-related changes in rho values or T1 and T2 relaxation values were observed. The animal model was probably unsuitable for demonstration of IFN effects. (orig.)

  7. The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Schimmack, Simon; Lawrence, Ben; Svejda, Bernhard; Alaimo, Daniele; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Kidd, Mark; Modlin, Irvin

    2012-05-15

    Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker. Functional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses. In BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior. Copyright © 2011 American Cancer Society.

  8. [Contemporary nuclear medicine diagnostics of neuroendocrine tumors].

    Science.gov (United States)

    2015-01-01

    The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline analogue labeled with iodine-131 or -123 (131/123I-MIBG); or 3) 99mTc(V)-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine). Conventional and contemporary (PET/ CT) somatostatin receptor detection showed identical high spe- cificity (92%), but conventional had very low sensitivity (52%) compared to PET/CT (97%). It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT) methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional (131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method ([18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA) shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET

  9. Primary neuroendocrine carcinoma of thymus: A rare cause of Cushing′s syndrome

    Directory of Open Access Journals (Sweden)

    Arora Raman

    2010-01-01

    Full Text Available Thymomas constitute majority of the thymic neoplasms. In contrast, neuroendocrine tumors (carcinoid and neuroendocrine carcinoma of thymus are extremely rare. Thymic carcinoids may present rarely with Cushing′s syndrome due to the ectopic production of adrenocorticotropic hormone (ACTH. Recognition of this association is imperative for appropriate management of patients. We describe three cases of rare atypical carcinoid tumor (neuroendocrine carcinoma of the thymus. Case 1, of a 26-year-old man presenting with Cushing′s syndrome, case 2 - a 23-year-old female with Cushingoid features, and Case 3 - a 39-year-old man complaining of progressively worsening dyspnea. Computed tomography (CT scans of chest in all three patients revealed anterior mediastinal mass. Excision of tumors and histological examination of the three tumors showed a carcinoid tumor with nuclear pleomorphism, increased mitotic activity and focal necrosis. The features suggested a diagnosis of atypical carcinoid tumor in all the three cases. The tumor cells in Cases 1 and 2 showed focal immunohistochemical staining for ACTH. Atypical carcinoid (neuroendocrine carcinoma, well-differentiated and moderately-differentiated of the thymus is a rare thymic tumor which carries a worse prognosis compared to thymoma and requires aggressive therapy. Hence, an accurate diagnosis is essential.

  10. Colonic neuroendocrine carcinoma in a child

    International Nuclear Information System (INIS)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes; Sathiapalan, Rajeev; Kofide, Amani; Tulbah, Asthma Mahmoud Mohamed; Al-Mehaidib, Ali

    2005-01-01

    A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia) presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea and low-grade fever. Radiological investigations with barium follow-through, CT, PET and octreotide scans revealed a primary caecal/ascending proximal colonic mass with liver and bony metastases. Urine screen for 5HIAA was positive. Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma. The radiological work-up and the usefulness of various imaging modalities in the diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated the primary tumour and the metastatic locations more vividly than the octreotide scan, which is currently considered to be the most specific imaging modality for neuroendocrine masses. (orig.)

  11. Neuroendocrine causes of amenorrhea--an update.

    Science.gov (United States)

    Fourman, Lindsay T; Fazeli, Pouneh K

    2015-03-01

    Secondary amenorrhea--the absence of menses for three consecutive cycles--affects approximately 3-4% of reproductive age women, and infertility--the failure to conceive after 12 months of regular intercourse--affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception.

  12. Neuroendocrine Causes of Amenorrhea—An Update

    Science.gov (United States)

    Fourman, Lindsay T.

    2015-01-01

    Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

  13. Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature.

    Science.gov (United States)

    Amorim, Gustavo Moreira; Quintella, Danielle; Cuzzi, Tullia; Rodrigues, Rosangela; Ramos-E-Silva, Marcia

    2015-01-01

    We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor) is discussed.

  14. Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gustavo Moreira Amorim

    2015-10-01

    Full Text Available We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor is discussed.

  15. Neuroendocrine regulation of appetitive ingestive behavior

    Directory of Open Access Journals (Sweden)

    Erin eKeen-Rhinehart

    2013-11-01

    Full Text Available Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e. food stored for future consumption and endogenous (i.e. body fat stores fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g. foraging, food hoarding, and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing. Quantifiable appetitive behaviors are part of many the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as NPY, AgRP and alpha-MSH, to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the neuroendocrine regulation of the motivation to engage in ingestive

  16. Skin manifestations of endocrine and neuroendocrine tumors.

    Science.gov (United States)

    Leventhal, Jonathan S; Braverman, Irwin M

    2016-06-01

    The skin signs of benign and malignant endocrine and neuroendocrine tumors are manifold and early identification of these dermatologic features is crucial in initiating timely diagnosis and management. This article reviews the salient cutaneous features of these tumors that arise in the classic endocrine glands, lung and gastrointestinal tract either as individual neoplasms or as part of a syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Neuroendocrine regulation of appetitive ingestive behavior.

    Science.gov (United States)

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E

    2013-11-15

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endogenous (i.e., body fat stores) fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g., foraging, food hoarding), and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing). Quantifiable appetitive behaviors are part of the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as neuropeptide Y (NPY), agouti-related protein (AgRP) and α-melanocyte stimulating hormone (α-MSH), to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the

  18. Neuroendocrine regulation of appetitive ingestive behavior

    OpenAIRE

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E.

    2013-01-01

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endo...

  19. Perinatal TCDD exposure alters developmental neuroendocrine system.

    Science.gov (United States)

    Ahmed, R G

    2011-06-01

    This study tested whether maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may disrupt the development of neuroendocrine system of their offspring during the perinatal period. TCDD (0.2 or 0.4 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1 to lactation day (LD) 30. Potential effects on neuroendocrine function were evaluated by measuring serum thyroid hormone levels in pregnant rats and their offspring and measuring some biochemical parameters in cerebellum of these offspring on GD 16 and 19, and LD 10, 20, and 30. In both treated groups, a decrease in serum thyroxine (T4), triiodothyronine (T3) and increase in thyrotropin (TSH) levels were noticed during the tested days in dams and offspring, as well as GH levels were decreased in offspring with respect to control group. In cerebellum of control offspring, the levels of monoamines, γ-aminobutyric acid (GABA) and acetylcholinesterase (AchE) were found to be increased from GD 16 to LD 30. The hypothyroid conditions due to both maternal administrations of TCDD produced inhibitory effects on monoamines and AchE, and stimulatory actions on GABA in cerebellum of offspring. These alterations were dose and age dependent. Overall, these results suggest that TCDD may act as neuroendocrine disruptor. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  20. Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors.

    Science.gov (United States)

    Moris, Dimitrios; Ntanasis-Stathopoulos, Ioannis; Tsilimigras, Diamantis I; Adam, Mohamad A; Yang, Chi-Fu Jeffrey; Harpole, David; Theocharis, Stamatios

    2018-01-01

    Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance. This review provides an insight into promising molecules and genes that are implicated in NET carcinogenesis, cell-cycle regulation, chromatin remodeling, apoptosis, intracellular cascades and cell-cell interactions. Additionally it supports a basis for classifying these tumors into categories that distinct molecular characteristics and disease natural history, which may have a direct impact on treatment options. In light of the recent approval of everolimus, mammalian target of rapamycin pathway inhibition and related biomarkers may play a central role in the treatment of pulmonary NETs. Future clinical trials that integrate molecular profiling are deemed necessary in order to treat patients with NET on a personalized basis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Conditional overexpression of the wild-type Gs alpha as the gsp oncogene initiates chronic extracellularly regulated kinase 1/2 activation and hormone hypersecretion in pituitary cell lines.

    Science.gov (United States)

    Romano, D; Magalon, K; Pertuit, M; Rasolonjanahary, R; Barlier, A; Enjalbert, A; Gerard, C

    2007-06-01

    In pituitary cells, activation of the cAMP pathway by specific G protein-coupled receptors controls differentiative functions and proliferation. Constitutively active forms of the alpha subunit of the heterotrimeric G(s) protein resulting from mutations at codon 201 or 227 (gsp oncogene) were first identified in 30-40% of human GH-secreting pituitary adenomas. This rate of occurrence suggests that the gsp oncogene is not responsible for initiating the majority of these tumors. Moreover, there is a large overlap between the clinical phenotypes observed in patients with tumors bearing the gsp oncogene and those devoid of this oncogene. To explore the role of G(s)alpha in GH-secreting adenomas, we obtained somatolactotroph GH4C1 cell lines by performing doxycycline-dependent conditional overexpression of the wild-type G(s)alpha protein and expression of the gsp oncogene. Although the resulting adenylyl cyclase and cAMP levels were 10-fold lower in the wild-type G(s)alpha-overexpressing cell line, a sustained MAPK ERK1/2 activation was observed in both cell lines. Overexpression of the wild-type G(s)alpha protein as the gsp oncogene initiated chronic activation of endogenous prolactin synthesis and release, as well as chronic activation of ERK1/2-sensitive human prolactin and GH promoters.

  2. Secretagogin is a new neuroendocrine marker in the human prostate

    DEFF Research Database (Denmark)

    Adolf, Katja; Wagner, Ludwig; Bergh, Anders

    2007-01-01

    marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue. METHODS: We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN......BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca(2+) binding protein, as a novel NE...... and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P marker in the prostate with more extended...

  3. Neuroendocrine tumor of the skin of head and neck

    Directory of Open Access Journals (Sweden)

    Stošić Srboljub

    2005-01-01

    Full Text Available Background. Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. Case report. We showed two cases (females of 89 and 70 years old hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the beginning of the treatment. The second patient with this neuroendocrine tumor with the high malignancy potential and huge regional metastasis, was treated surgically, and died a month and a half after the operation. Conclusion. These two cases confirmed the aggressive and recidivant growth of this tumor with the difficult pathologic investigation, and the extremely bad prognosis inspite of the treatment.

  4. Neuroendocrine underpinnings of sex differences in circadian timing systems.

    Science.gov (United States)

    Yan, Lily; Silver, Rae

    2016-06-01

    There are compelling reasons to study the role of steroids and sex differences in the circadian timing system. A solid history of research demonstrates the ubiquity of circadian changes that impact virtually all behavioral and biological responses. Furthermore, steroid hormones can modulate every attribute of circadian responses including the period, amplitude and phase. Finally, desynchronization of circadian rhythmicity, and either enhancing or damping amplitude of various circadian responses can produce different effects in the sexes. Studies of the neuroendocrine underpinnings of circadian timing systems and underlying sex differences have paralleled the overall development of the field as a whole. Early experimental studies established the ubiquity of circadian rhythms by cataloging daily and seasonal changes in whole organism responses. The next generation of experiments demonstrated that daily changes are not a result of environmental synchronizing cues, and are internally orchestrated, and that these differ in the sexes. This work was followed by the revelation of molecular circadian rhythms within individual cells. At present, there is a proliferation of work on the consequences of these daily oscillations in health and in disease, and awareness that these may differ in the sexes. In the present discourse we describe the paradigms used to examine circadian oscillation, to characterize how these internal timing signals are synchronized to local environmental conditions, and how hormones of gonadal and/or adrenal origin modulate circadian responses. Evidence pointing to endocrinologically and genetically mediated sex differences in circadian timing systems can be seen at many levels of the neuroendocrine and endocrine systems, from the cell, the gland and organ, and to whole animal behavior, including sleep/wake or rest/activity cycles, responses to external stimuli, and responses to drugs. We review evidence indicating that the analysis of the circadian

  5. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  6. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: tales from a teleost model

    DEFF Research Database (Denmark)

    Azeredo, Rita; Machado, M.; Afonso, A.

    2017-01-01

    cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together with a high production of brain monoamine and cortisol levels, suggests that tryptophan might mediate regulatory mechanisms of neuroendocrine and immune systems...... the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2x dietary requirement level) or a control......, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led...

  7. Triple malignancy in a single patient including a cervical carcinoma, a basal cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-09-01

    Full Text Available Abstract Introduction The occurrence of multiple primary cancers is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported. Case presentation We report here a case of a 78-year-old Moroccan woman presenting initially with a synchronous double malignancy, the first in her cervix and the second in her skin. Our patient was treated with radiation therapy for both tumors and remained in good control for 17 years, when she developed a metastatic disease from a neuroendocrine carcinoma of an unknown primary site. Conclusions Although the association of multiple primary cancers can be considered a rare occurrence, improving survival in cancer patients has made this situation more frequent.

  8. Effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella

    DEFF Research Database (Denmark)

    Cymborowski, B.; Sørensen, Ilona Kryspin

    1975-01-01

    1. Studies were made on the effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella. It was shown that resperine greatly restricts the development of this insect. 2. Reserpine causes inhibition of the activity of the neurosecretory cells of pars intercerebralis....... mellonella. 4. A discussion is given of the probable participation of ecdysone in regulation of the level of sodium and potassium ions in the haemolymph of G. mellonella....

  9. Primary neuroendocrine carcinoma of the thymus | Gaude | Nigerian ...

    African Journals Online (AJOL)

    Primary neuroendocrine tumors of the thymus, previously known as carcinoid tumors of the thymus, are unusual and rare tumors, and prognosis for these patients has been difficult to predict. We hereby report a case of primary neuroendocrine tumor of the thymus that had an aggressive and fatal course in spite of surgical ...

  10. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... these PET tracers further....

  11. Chronic diarrhea as presenting symptom for a metastasic neuroendocrine tumor

    International Nuclear Information System (INIS)

    Hani A, Albis Cecilia; Garcia A, Jairo Alberto

    2007-01-01

    We describe the clinical case of a 74 years old female patient presenting with a watery diarrhea syndrome, having severe hypokalaemia and liver metastases. In her necropsy a pancreatic neuroendocrine tumor was found. We present a literature review about pancreas neuroendocrine tumours, focusing in the VIPoma, which may correspond with the clinical features of this particular patient

  12. Quantitative proteomics in teleost fish: insights and challenges for neuroendocrine and neurotoxicology research.

    Science.gov (United States)

    Martyniuk, Christopher J; Popesku, Jason T; Chown, Brittany; Denslow, Nancy D; Trudeau, Vance L

    2012-05-01

    Neuroendocrine systems integrate both extrinsic and intrinsic signals to regulate virtually all aspects of an animal's physiology. In aquatic toxicology, studies have shown that pollutants are capable of disrupting the neuroendocrine system of teleost fish, and many chemicals found in the environment can also have a neurotoxic mode of action. Omics approaches are now used to better understand cell signaling cascades underlying fish neurophysiology and the control of pituitary hormone release, in addition to identifying adverse effects of pollutants in the teleostean central nervous system. For example, both high throughput genomics and proteomic investigations of molecular signaling cascades for both neurotransmitter and nuclear receptor agonists/antagonists have been reported. This review highlights recent studies that have utilized quantitative proteomics methods such as 2D differential in-gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) in neuroendocrine regions and uses these examples to demonstrate the challenges of using proteomics in neuroendocrinology and neurotoxicology research. To begin to characterize the teleost neuroproteome, we functionally annotated 623 unique proteins found in the fish hypothalamus and telencephalon. These proteins have roles in biological processes that include synaptic transmission, ATP production, receptor activity, cell structure and integrity, and stress responses. The biological processes most represented by proteins detected in the teleost neuroendocrine brain included transport (8.4%), metabolic process (5.5%), and glycolysis (4.8%). We provide an example of using sub-network enrichment analysis (SNEA) to identify protein networks in the fish hypothalamus in response to dopamine receptor signaling. Dopamine signaling altered the abundance of proteins that are binding partners of microfilaments, integrins, and intermediate filaments, consistent with data suggesting dopaminergic

  13. Quantitative proteomics in teleost fish: Insights and challenges for neuroendocrine and neurotoxicology research

    Science.gov (United States)

    Martyniuk, Christopher J.; Popesku, Jason T.; Chown, Brittany; Denslow, Nancy D.; Trudeau, Vance L.

    2012-01-01

    Neuroendocrine systems integrate both extrinsic and intrinsic signals to regulate virtually all aspects of an animal’s physiology. In aquatic toxicology, studies have shown that pollutants are capable of disrupting the neuroendocrine system of teleost fish, and many chemicals found in the environment can also have a neurotoxic mode of action. Omics approaches are now used to better understand cell signaling cascades underlying fish neurophysiology and the control of pituitary hormone release, in addition to identifying adverse effects of pollutants in the teleostean central nervous system. For example, both high throughput genomics and proteomic investigations of molecular signaling cascades for both neurotransmitter and nuclear receptor agonists/antagonists have been reported. This review highlights recent studies that have utilized quantitative proteomics methods such as 2D differential in-gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) in neuroendocrine regions and uses these examples to demonstrate the challenges of using proteomics in neuroendocrinology and neurotoxicology research. To begin to characterize the teleost neuroproteome, we functionally annotated 623 unique proteins found in the fish hypothalamus and telencephalon. These proteins have roles in biological processes that include synaptic transmission, ATP production, receptor activity, cell structure and integrity, and stress responses. The biological processes most represented by proteins detected in the teleost neuroendocrine brain included transport (8.4%), metabolic process (5.5%), and glycolysis (4.8%). We provide an example of using sub-network enrichment analysis (SNEA) to identify protein networks in the fish hypothalamus in response to dopamine receptor signaling. Dopamine signaling altered the abundance of proteins that are binding partners of microfilaments, integrins, and intermediate filaments, consistent with data suggesting dopaminergic

  14. Role of neuroendocrine and neuroimmune mechanisms in chronic inflammatory rheumatic diseases--the 10-year update.

    Science.gov (United States)

    Straub, Rainer H; Bijlsma, Johannes W J; Masi, Alfonse; Cutolo, Maurizio

    2013-12-01

    Neuroendocrine immunology in musculoskeletal diseases is an emerging scientific field. It deals with the aspects of efferent neuronal and neurohormonal bearing on the peripheral immune and musculoskeletal systems. This review aims to add new information that appeared since 2001. The following PubMed search sentence was used to find a total of 15,462 references between 2001 and March 2013: "(rheum* OR SLE OR vasculitis) AND (nerve OR hormone OR neurotransmitter OR neuropeptide OR steroid)." In a continuous process, year by year, this search strategy yielded relevant papers that were screened and collected in a database, which build the platform of this review. The main findings are the anti-inflammatory role of androgens, the loss of androgens (androgen drain), the bimodal role of estrogens (support B cells and inhibit macrophages and T cells), increased conversion of androgens to estrogens in inflammation (androgen drain), disturbances of the gonadal axis, inadequate amount of HPA axis hormones relative to inflammation (disproportion principle), biologics partly improve neuroendocrine axes, anti-corticotropin-releasing hormone therapies improve inflammation (antalarmin), bimodal role of the sympathetic nervous system (proinflammatory early, anti-inflammatory late-most probably due to catecholamine-producing local cells), anti-inflammatory role of alpha melanocyte-stimulating hormone, vasoactive intestinal peptide, and the Vagus nerve via α7 nicotinergic receptors. Circadian rhythms of hypothalamic origin are responsible for circadian rhythms of symptoms (neuroimmune link revealed). Important new pain-sensitizing immunological pathways were found in the last decade. The last decade brought much new information that gave birth to the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets. In addition, a new theory linked evolutionary medicine, neuroendocrine regulation of distribution of energy-rich fuels, and volume

  15. [Neuroendocrine effect of sex hormones].

    Science.gov (United States)

    Babichev, V N

    2005-01-01

    The paper provides a generalization of data and the results of own experiments on influence ovarian steroids on the hypothalamus and other brain areas related to reproduction. Ovarian hormones have widespread effects throughout the brain: on catecholaminergic neurons and serotonergic pathways and the basal forebrain cholinergic system, as well as the hipocampus, spinal cord, nigrostriatal and mesolimbic system, in addition to glial cells and blood-brain barrier. The widespread influences of these various neuronal systems ovarian steroids have measurable effects on mood and affect as well as on cognition, with implications for dementia. There are developmentally programmed sex differenced in hippocampal structure that may help to explain differences in the strategies which male and female rats use to solve spatial navigation problems. The multiple sites and mechanisms of estrogen action in brain underlie a variety of importants effects on cognitive and other brain functions--coordination of movement, pain, affective state, as well as possible protection in Alzheimer's disease. Estrogen withdrawal after natural or surgical menopause can lead to a host of changes in brain function and behavior.

  16. The neuroendocrine control of the innate immune system in health and brain diseases.

    Science.gov (United States)

    Bellavance, Marc-André; Rivest, Serge

    2012-07-01

    The innate immune reaction takes place in the brain during immunogenic challenges, injury, and disease. Such a response is highly regulated by numerous anti-inflammatory mechanisms that may directly affect the ultimate consequences of such a reaction within the cerebral environment. The neuroendocrine control of this innate immune system by glucocorticoids is critical for the delicate balance between cell survival and damage in the presence of inflammatory mediators. Glucocorticoids play key roles in regulating the expression of inflammatory genes, and they also have the ability to modulate numerous functions that may ultimately lead to brain damage or repair after injury. Here we review these mechanisms and discuss data supporting both neuroprotective and detrimental roles of the neuroendocrine control of innate immunity. © 2012 John Wiley & Sons A/S.

  17. Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2013-01-01

    Full Text Available Neuroendocrine tumors (NETs are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.

  18. Novel mechanisms for neuroendocrine regulation of aggression.

    Science.gov (United States)

    Soma, Kiran K; Scotti, Melissa-Ann L; Newman, Amy E M; Charlier, Thierry D; Demas, Gregory E

    2008-10-01

    In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives gonadal hormones, primarily testosterone, which modulate relevant neural circuits. While this paradigm has been extremely useful, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when gonads are regressed and circulating testosterone levels are typically low. Studies in birds and mammals suggest that an adrenal androgen precursor-dehydroepiandrosterone (DHEA)-may be important for the expression of aggression when gonadal testosterone synthesis is low. Circulating DHEA can be metabolized into active sex steroids within the brain. Another possibility is that the brain can autonomously synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative neuroendocrine mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the "costs" of high circulating testosterone during particular seasons. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. Such mechanisms may be important for the control of aggression in many vertebrate species, including humans.

  19. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system.

    Science.gov (United States)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L; Jung, Anita G; Gether, Ulrik; Kjaerulff, Ole

    2009-11-20

    The protein interacting with C kinase 1 (PICK1) protein was first identified as a novel binding partner for protein kinase C. PICK1 contains a membrane-binding BAR domain and a PDZ domain interacting with many synaptic proteins, including the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1-expressing cells form a subpopulation of neurons. PICK1 immunoreactivity was neither detected in glutamatergic nor in dopaminergic neurons. Also, we observed PICK1 expression in only a few GABAergic neurons, located in the antennal lobe. In contrast, we detected robust PICK1 immunolabeling of peptidergic neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells also occurs in mammals, as it was also observed in a rat insulinoma cell line derived from pancreatic beta-cells. At the subcellular level, PICK1 was found in the perinuclear zone but surprisingly not in synaptic domains. We conclude that PICK1 may serve an important role in the neuroendocrine system both in insects and vertebrates.

  20. Neuroendocrine Tumors of the Esophagus: State of the Art in Diagnostic and Therapeutic Management.

    Science.gov (United States)

    Schizas, Dimitrios; Mastoraki, Aikaterini; Kirkilesis, George I; Sioulas, Athanasios D; Papanikolaou, Ioannis S; Misiakos, Evangelos P; Arkadopoulos, Nikolaos; Liakakos, Theodore

    2017-12-01

    Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms composed of cells containing dense-core neuroendocrine secretory granules in their cytoplasm. NETs of the esophagus are exceedingly uncommon, with a parallel absence of data published on clinical features, prognosis, and proposed treatment strategies. As relevant classification is not well-established, knowledge acquired in NETs of lung and gastrointestinal sites usually guides esophageal NET management. Associated subtypes are divided based upon shared neuroendocrine features into small and large cell NET, typical and atypical carcinoid. Common presenting symptoms include dysphagia, abdominal discomfort, weight loss, melena, and on occasion, signs of carcinoid syndrome. Endoscopic findings describe a polypoid, nodular elevated lesion with an overlying surface depicted as mostly smooth and glistening. Disease metastasis is assessed using anatomical imaging, including computed tomography (CT), endoscopic ultrasonography (EUS), and positron emission tomography (PET)-CT. Prognosis is influenced by the extent of lymph node metastasis and potential lymphovascular invasion. Furthermore, proliferative activity, estimated using mitotic count or Ki-67 immunostaining, has been suggested as a significant prognostic parameter. Therapeutic approach depends on clinical staging. Nevertheless, currently, a specific treatment algorithm for esophageal NETs has not been elucidated. Endoscopic resection has been proposed in NETs less than 1 cm in size with absence of regional lymph node metastasis, while surgical excision combined with adjuvant chemotherapy remains the treatment of choice.

  1. Gut Microbiota: The Conductor in the Orchestra of Immune-Neuroendocrine Communication.

    Science.gov (United States)

    El Aidy, Sahar; Dinan, Timothy G; Cryan, John F

    2015-05-01

    It is well established that mammals are so-called super-organisms that coexist with a complex microbiota. Growing evidence points to the delicacy of this host-microbe interplay and how disruptive interventions could have lifelong consequences. The goal of this article was to provide insights into the potential role of the gut microbiota in coordinating the immune-neuroendocrine cross-talk. Literature from a range of sources, including PubMed, Google Scholar, and MEDLINE, was searched to identify recent reports regarding the impact of the gut microbiota on the host immune and neuroendocrine systems in health and disease. The immune system and nervous system are in continuous communication to maintain a state of homeostasis. Significant gaps in knowledge remain regarding the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. Recent evidence from experimental animal models found that stimulation of subsets of immune cells by the gut microbiota, and the subsequent cross-talk between the immune cells and enteric neurons, may have a major impact on the host in health and disease. Data from rodent models, as well as from a few human studies, suggest that the gut microbiota may have a major role in coordinating the communication between the immune and neuroendocrine systems to develop and maintain homeostasis. However, the underlying mechanisms remain unclear. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, the immune system, and the neuroendocrine system in a network of communication to eventually translate these findings to the human situation, both in health and disease. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  2. Neuroendocrine tumor presenting like lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  3. Neuroendocrine tumor of the inguinal node: A very rare presentation

    Directory of Open Access Journals (Sweden)

    Niharika Bisht

    2017-12-01

    Full Text Available Neuroendocrine tumors are a broad family of tumors arising most commonly in the gastrointestinal tract and the bronchus pulmonary tree. The other common sounds are the parathyroid, pituitary and adrenal gland. Inguinal node as a primary presentation of a neuroendocrine tumor is an extremely rare presentation. We present the case of a 43-year-old-male who presented with the complaints of an inguinal node swelling without any other symptoms and on further evaluation was diagnosed to have a non-metastatic neuroendocrine tumor of the inguinal node. He was treated with a combination of chemotherapy and surgery and is presently awaiting completion chemotherapy.

  4. Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

    Science.gov (United States)

    Pelosi, Giuseppe; Papotti, Mauro; Rindi, Guido; Scarpa, Aldo

    2014-06-01

    Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations

  5. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

    Directory of Open Access Journals (Sweden)

    Akihiro Ohmoto

    2017-01-01

    Full Text Available Pancreatic neuroendocrine neoplasms (pNENs are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC, will be needed to improve the prognosis.

  6. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    Directory of Open Access Journals (Sweden)

    Fabiana Policeni

    2016-01-01

    Full Text Available Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient′s left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI.

  7. Neuroendocrine dysfunction in fibromyalgia and migraine.

    Science.gov (United States)

    Valença, Marcelo Moraes; Medeiros, Fabíola Lys; Martins, Hugo A; Massaud, Rodrigo Meirelles; Peres, Mario F P

    2009-10-01

    Fibromyalgia (FM) and migraine are common chronic disorders that predominantly affect women. The prevalence of headache in patients with FM is high (35%-88%), with migraine being the most frequent type. A particular subgroup of patients with FM (approximately half) presents with a combined clinical form of these two painful disorders, which may exhibit a different manner of progression regarding symptomatology and impact on daily activities. This article reviews several common aspects of the pathophysiology regarding pain control mechanisms and neuroendocrine dysfunction occurring in FM and migraine, particularly in the chronic form of the latter. We also discuss the participation of hypothalamic and brainstem centers of pain control, the putative role played by neurotransmitters or neuromodulators on central sensitization, and changes in their levels in the cerebrospinal fluid. Understanding their mechanisms will help to establish new treatment strategies for treating these disabling brain disorders.

  8. [Neuroendocrine disturbances after acquired brain damage].

    Science.gov (United States)

    Kreitschmann-Andermahr, I; Brabant, G

    2011-04-01

    Hypopituitarism is not a rare disease and its clinical signs and symptoms deserve the attention of the clinically practising neurologist. Next to the classical cause of hypopituitarism mediated by tumours of the hypothalamo-pituitary region, a number of recent articles have highlighted the high frequency of central endocrine disturbances in patients with brain damage, i. e. not only after traumatic brain injury and subarachnoid haemorrhage but also as a consequence of the treatment of childhood brain tumours. This article provides an overview of the clinical symptomatology and pathophysiology of hypopituitarism as well as the current knowledge about neuroendocrine disturbances in the adult patient suffering from the above-mentioned disorders. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

    Science.gov (United States)

    Sargos, P; Ferretti, L; Gross-Goupil, M; Orre, M; Cornelis, F; Henriques de Figueiredo, B; Houédé, N; Merino, C; Roubaud, G; Dallaudiére, B; Richaud, P; Fléchon, A

    2014-09-01

    Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

  10. Hypothesis: Musculin is a hormone secreted by skeletal muscle, the body's largest endocrine organ. Evidence for actions on the endocrine pancreas to restrain the beta-cell mass and to inhibit insulin secretion and on the hypothalamus to co-ordinate the neuroendocrine and appetite responses to exercise.

    Science.gov (United States)

    Engler, Dennis

    2007-01-01

    Recent studies indicate that skeletal muscle may act as an endocrine organ by secreting interleukin-6 (IL-6) into the systemic circulation. From an analysis of the actions of IL-6 and of additional literature, we postulate that skeletal muscle also secretes an unidentified hormone, which we have named Musculin (Latin: musculus = muscle), which acts on the pancreatic beta-cell to restrain the size of the (beta-cell mass and to tonically inhibit insulin secretion and biosynthesis. It is suggested that the amount of Musculin secreted is determined by, and is positively correlated with, the prevailing insulin sensitivity of skeletal muscle, thereby accounting for the hyperinsulinemia that occurs in insulin resistant disorders such as type 2 diabetes mellitus, obesity, and the polycystic ovary syndrome. In addition, it is postulated that Musculin acts on the hypothalamus (arcuate nucleus, dorsomedial hypothalamic nucleus) to co-ordinate the neuroendocrine and appetite responses to exercise. However, the possibilities that Musculin may act on additional central nervous system sites and that an additional hormone(s) may be responsible for these actions are not excluded. It is suggested that a search be made for Musculin, since analogues of such a substance may be of therapeutic benefit in the treatment of the current global diabetes and obesity epidemic.

  11. The role of neuroendocrine pathways in prognosis after stroke.

    Science.gov (United States)

    El Husseini, Nada; Laskowitz, Daniel T

    2014-02-01

    A number of neuroendocrine changes have been described after stroke, which may serve adaptive or deleterious functions. The neuroendocrine changes include activation of the hypothalamo-pituitary-adrenal axis, sympathetic nervous system and alterations of several hormonal levels. Alterations of the HPA axis, increased catecholamines, natriuretic peptides and, decreased melatonin and IGF-1 levels are associated with poor post-stroke outcome, although there is no definitive proof of causality. Therefore, it remains to be established whether alteration of neuroendocrine responses could be used as a potential therapeutic target to improve stroke outcome. This article gives an overview of the major neuroendocrine pathways altered by stroke and highlights their potential for clinical use and further neurotherapeutic development by summarizing the evidence for their association with stroke outcome including functional outcome, post-stroke infection, delirium, depression and stroke-related myocardial injury.

  12. Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children

    Directory of Open Access Journals (Sweden)

    Inês Pinto

    2017-04-01

    Conclusion: These results highlight the importance of taking into account family functioning, parental mental state and gender, when investigating neuroendocrine biomarkers in obese children associated with symptoms of anxiety and depression.

  13. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Francesco, E-mail: f.tonelli@dfc.unifi.it; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)

    2012-05-07

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  14. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  15. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  16. Ghrelin and pre-proghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis Grelina e pré-progrelina em tumores neuroendócrinos do estômago associados à gastrite atrófica do corpo

    Directory of Open Access Journals (Sweden)

    Letícia Figueiredo Moreira

    2010-08-01

    Full Text Available INTRODUCTION: Ghrelin is a 28 amino acid peptide secreted mainly by endocrine cells present in the gastric mucosa and acknowledged as an endogenous releaser of growth hormone. The immunohistochemical expression of ghrelin has been described in neuroendocrine tumors, and it is believed that may exert modulating action related to the growth of these tumors. OBJECTIVE: To study the presence of ghrelin and preproghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis. METHODS: Endoscopic biopsies from 15 patients with neuroendocrine tumor of the gastric mucosa associated with atrophic body gastritis were performed for immunohistochemistry, and specific chromogranin, ghrelin and preproghrelin antibodies were applied. The immunohistochemical expression was assessed in tumor cells and endocrine micronodular hyperplasia present in mucosa adjacent to the tumor, and it was classified in relation to the number of stained cells. RESULTS: Chromogranin was positive in 14 out of 15 tumors. Ghrelin and preproghrelin immunoreactive cells were detected in 11 (73% and 13 (87% tumors, respectively. There was a significant correlation between the immunohistochemical results of both antigen expressions (kappa = 81%. Ghrelin and preproghrelin expression was detected in hyperplastic nodules present in the mucosa adjacent to the tumor in seven and eight cases, respectively. There was no correlation between these results and those observed in neoplastic cells. CONCLUSION: Ghrelin and preproghrelin immunoreactive cells may be found in variable number in Type I neuroendocrine gastric tumors and in hyperplastic nodules associated with these tumors. However, it remains unclear what role these peptides play on the development of these tumors.INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos, reconhecido como liberador endógeno do hormônio do crescimento, sendo secretado principalmente por células endócrinas da mucosa g

  17. The coordinated expression, interaction and evolution of the neuroendocrine genes.

    Science.gov (United States)

    Tiwary, Basant K

    2012-11-01

    The neuroendocrine system is a complex biological system controlled by various neuropeptides and hormones. The evolution and network properties of neuroendocrine genes are analyzed along with their expression profiles. The neuroendocrine genes show very similar expression profiles and local network properties across a wide range of tissues consistent with the physiological roles of their proteins. Moreover, the coordinated evolution of 10 neuroendocrine genes involved in mammalian reproduction and homeostasis is demonstrated using several methods, such as correlated evolution, relative-rate test, relative-ratio test and codon usage bias. The neuroendocrine genes seem to evolve predominantly under similar selective strengths and regimes of purifying selection, which is well reflected in their evolutionary fingerprints. This result demonstrates for the first time a key role of natural selection in creating and maintaining a well-designed neuroendocrine system at the genomic level. It also indicates that component properties of a complex system at a higher physiological scale may determine component properties at a lower genomic scale and/or vice versa.

  18. Behavioral and neuroendocrine characteristics of the night-eating syndrome.

    Science.gov (United States)

    Birketvedt, G S; Florholmen, J; Sundsfjord, J; Osterud, B; Dinges, D; Bilker, W; Stunkard, A

    1999-08-18

    Investigators first described the night-eating syndrome (NES), which consists of morning anorexia, evening hyperphagia, and insomnia, in 1955, but, to our knowledge, this syndrome has never been subjected to careful clinical study. To characterize NES on the basis of behavioral characteristics and neuroendocrine data. A behavioral observational study was conducted between January 1996 and June 1997 in a weight and eating disorders program at the University of Pennsylvania. A neuroendocrine study was conducted from May through August 1997 at the Clinical Research Center of the University Hospital, Tromso, Norway. The behavioral study included 10 obese subjects who met criteria for NES and 10 matched control subjects. The neuroendocrine study included 12 night eaters and 21 control subjects. Behavioral study subjects were observed for 1 week on an outpatient basis, and neuroendocrine study subjects were observed during a 24-hour period in the hospital. The behavioral study measured timing of energy intake, mood level, and sleep disturbances. The neuroendocrine study measured circadian levels of plasma melatonin, leptin, and cortisol. In the behavioral study, compared with control subjects, night eaters had more eating episodes in the 24 hours (mean [SD], 9.3 [0.6] vs 4.2 [0.2]; Pvs 15%; Pmelatonin and leptin levels (Pcortisol (P = .001). A coherent pattern of behavioral and neuroendocrine characteristics was found in subjects with NES.

  19. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Julia Lipianskaya

    2014-08-01

    Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

  20. Pulmonary neuroendocrine carcinoma mimicking neurocysticercosis: a case report.

    Science.gov (United States)

    Lam, John C; Robinson, Stephen R; Schell, Andrew; Vaughan, Stephen

    2016-06-02

    Neurocysticercosis occurs when the eggs of the pork tapeworm (Taenia solium) migrate and hatch into larvae within the central nervous system. Neurocysticercosis is the most common cause of seizures in the developing world and is characterized on brain imaging by cysts in different stages of evolution. In Canada, cases of neurocysticercosis are rare and most of these patients acquire the disease outside of Canada. We report the case of a patient with multiple intracranial lesions whose history and diagnostic imaging were consistent with neurocysticercosis. Pathological investigations ultimately demonstrated that her brain lesions were secondary to malignancy. Brain metastases are considered to be the most common cause of intracranial cystic lesions. We present the case of a 60-year-old Canadian-born Caucasian woman with a subacute history of ataxia, lower extremity hyper-reflexia, and otalgia who resided near a pig farm for most of her childhood. Computed tomography and magnetic resonance imaging showed that she had multiple heterogeneous intracranial cysts, suggestive of neurocysticercosis. Despite a heavy burden of disease, serological tests for cysticercosis were negative. This result and a lack of the central scolices on neuroimaging that are pathognomonic of neurocysticercosis prompted whole-body computed tomography imaging to identify another etiology. The whole-body computed tomography revealed right hilar lymphadenopathy associated with soft tissue nodules in her chest wall and abdomen. A biopsy of an anterior chest wall nodule demonstrated high-grade poorly differentiated carcinoma with necrosis, which stained strongly positive for thyroid transcription factor-1 and synaptophysin on immunohistochemistry. A diagnosis of stage 4 metastatic small cell neuroendocrine carcinoma was made and our patient was referred for oncological palliative treatment. This case illustrates the importance of the diagnostic approach to intracranial lesions. Our patient

  1. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles.

    Science.gov (United States)

    Grippo, Angela J; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks of social isolation versus paired housing. In Experiment 1, oxytocin-immunoreactive cell density was higher in the hypothalamic paraventricular nucleus (PVN) and plasma oxytocin was elevated in isolated females, but not in males. In Experiment 2, sucrose intake, used as an operational definition of hedonia, was reduced in both sexes following 4 weeks of isolation. Animals then received a resident-intruder test, and were sacrificed either 10 min later for the analysis of circulating hormones and peptides, or 2h later to examine neural activation, indexed by c-Fos expression in PVN cells immunoreactive for oxytocin or corticotropin-releasing factor (CRF). Compared to paired animals, plasma oxytocin, ACTH and corticosterone were elevated in isolated females and plasma oxytocin was elevated in isolated males, following the resident-intruder test. The proportion of cells double-labeled for c-Fos and oxytocin or c-Fos and CRF was elevated in isolated females, and the proportion of cells double-labeled for c-Fos and oxytocin was elevated in isolated males following this test. These findings suggest that social isolation induces behavioral and neuroendocrine responses relevant to depression in male and female prairie voles, although neuroendocrine responses in females may be especially sensitive to isolation.

  2. Effects of Enteromyxum scophthalmi experimental infection on the neuroendocrine system of turbot, Scophthalmus maximus (L.).

    Science.gov (United States)

    Losada, A P; Bermúdez, R; Faílde, L D; Di Giancamillo, A; Domeneghini, C; Quiroga, M I

    2014-10-01

    Enteromyxum scophthalmi is an intestinal myxosporean parasite responsible for serious outbreaks in turbot Scophthalmus maximus (L.) culture, in North-western Spain. The disease affects the digestive tract, provokes severe catarrhal enteritis, emaciation and high rates of mortality. The digestive parasitization triggers a response with the coordinate participation of immune and neuroendocrine systems through the action of peptides released by enteroendocrine cells and present in nervous elements, acting as neuro-immune modulators. The present study was designed to assess the response of the turbot neuroendocrine system against E. scophthalmi infection. Immunohistochemical tests were applied to sections of the gastrointestinal tract of uninfected and E. scophthalmi-infected turbot to characterize the presence of bombesin (BOM), glucagon (GLUC), somatostatin (SOM), leu-enkephalin (LEU) and met-enkephalin (MET). The occurrence of E. scophthalmi in the turbot gastrointestinal tract increased the number of enteroendocrine cells immunoreactive to SOM, LEU and MET. On the other hand, BOM and GLUC immunoreactive cells were less numerous in the gastrointestinal tract of the parasitized turbot. Scarce immunoreactivity to BOM, GLUC and SOM was observed in nerve fibres and neurons of the myenteric plexus of control and infected fish. The results indicate that E. scophthalmi infection in turbot induced changes in the neuroendocrine system, with the diminution of the anorexigenic peptides BOM and GLUC; the increase of enkephalins, related to pro-inflammatory processes; and the increase of SOM, which may cause inhibitory effects on the immune response, constituting a compensatory mechanism to the exacerbated response observed in E. scophthalmi-infected turbot. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Review of radionuclide treatment for neuroendocrine tumors

    International Nuclear Information System (INIS)

    Jeong, Hwan Jeong

    2006-01-01

    Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. 131 I-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. 111 In, 90 Y and 177 Lu radiolabelled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. For all radionuclides used for therapy, long-tem and survival statistics are not yet available and only partial tumour responses have been obtained using 131 I-MIBG and 111 In-octreotide. Experimental results using 90 Y-DOTA-lanreotide as well as 90 Y-DOTA-D -Phe1-Tyr 3 -octreotide and/or 177 Lu-DOTA-Tyr 3 -octreotate have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy. It may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation

  4. GEPNETs update: Radionuclide therapy in neuroendocrine tumors.

    Science.gov (United States)

    van der Zwan, Wouter A; Bodei, Lisa; Mueller-Brand, Jan; de Herder, Wouter W; Kvols, Larry K; Kwekkeboom, Dik J

    2015-01-01

    Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, 'targeted' therapies. They also compare favorably to PFS data for liver-directed therapies. Two decades after the introduction of PRRT, there is a growing need for randomized controlled trials comparing PRRT to 'standard' treatment, that is treatment with agents that have proven benefit when tested in randomized trials. Combining PRRT with liver-directed therapies or with targeted therapies could improve treatment results. The question to be answered, however, is whether a combination of therapies performed within a limited time-span from one another results in a better PFS than a strategy in which other therapies are reserved until after (renewed) tumor progression. Randomized clinical trials comparing PRRT with other treatment modalities should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs. © 2015 European Society of Endocrinology.

  5. Diagnosis and Management of Rectal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Shreya Chablaney

    2017-11-01

    Full Text Available The incidence of rectal neuroendocrine tumors (NETs has increased by almost ten-fold over the past 30 years. There has been a heightened awareness of the malignant potential of rectal NETs. Fortunately, many rectal NETs are discovered at earlier stages due to colon cancer screening programs. Endoscopic ultrasound is useful in assessing both residual tumor burden after retrospective diagnosis and tumor characteristics to help guide subsequent management. Current guidelines suggest endoscopic resection of rectal NETs ≤10 mm as a safe therapeutic option given their low risk of metastasis. Although a number of endoscopic interventions exist, the best technique for resection has not been identified. Endoscopic submucosal dissection (ESD has high complete and en-bloc resection rates, but also an increased risk of complications including perforation. In addition, ESD is only performed at tertiary centers by experienced advanced endoscopists. Endoscopic mucosal resection has been shown to have variable complete resection rates, but modifications to the technique such as the addition of band ligation have improved outcomes. Prospective studies are needed to further compare the available endoscopic interventions, and to elucidate the most appropriate course of management of rectal NETs.

  6. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

    2016-04-15

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  7. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  8. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...... and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging. METHODS: The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline...

  9. Impact of Prenatal Stress on Neuroendocrine Programming

    Directory of Open Access Journals (Sweden)

    Odile Viltart

    2007-01-01

    programming strongly, notably when hormonal surges occur during sensitive periods of development, so-called developmental windows of vulnerability. Stressful events occurring during the perinatal period may impinge on various aspects of the neuroendocrine programming, subsequently amending the offspring's growth, metabolism, sexual maturation, stress responses, and immune system. Such prenatal stress-induced modifications of the phenotypic plasticity of the progeny might ultimately result in the development of long-term diseases, from metabolic syndromes to psychiatric disorders. Yet, we would like to consider the outcome of this neuroendocrine programming from an evolutionary perspective. Early stressful events during gestation might indeed shape internal parameters of the developing organisms in order to adapt the progeny to its everyday environment and thus contribute to an increased reproductive success, or fitness, of the species. Moreover, parental care, adoption, or enriched environments after birth have been shown to reverse negative long-term consequences of a disturbed gestational environment. In this view, considering the higher potential for neonatal plasticity within the brain in human beings as compared to other species, long-term consequences of prenatal stress might not be as inexorable as suggested in animal-based studies published to date.

  10. Neuroendocrine and Metabolic Disorders in Bulimia Nervosa.

    Science.gov (United States)

    Milano, Walter; Capasso, Anna

    2017-12-11

    Bulimia nervosa, is an eating disorder characterized by excessive influence of weight and body shape on the levels of self-esteem, with pervasive feelings of failure and inadequacy. The eating is characterized by the presence of episodes of uncontrolled eating (Binge), during which the person ingests mass wide variety of foods and the feeling of not being able to stop eating. This review focuses on the metabolic and hormonal alterations in the in bulimia nervosa. A literature search was conducted using the electronic database Medline and PubMed and with additional hand searches through the reference list obtained from the articles found. Journal were searched up to 2015. Inclusion criteria were: 1) full text available in English; 2) published in a peer-reviewed journal and using the following keywords: neurotrasmitters (AgRP, BDNF, αMSH, NP Y, endocannabinoids, adiponectin, CCK, ghrelin, GLP-1, insulin, leptin, PP, PYY), hormones (FSH, LH, estrogen, progesterone, testosterone) and bulimia nervosa, eating disorders. All data reported in the present review indicated that changes in the central and peripheral neuroendocrine equilibria may favor the onset and influence the course and prognosis of an DA. However, it is still questionable whether the alterations of the peptides and hormones regulating the mechanisms of eating behavior are the cause or consequence of a compromised diet. The results of the present review indicate that the altered balance of the various peptides or hormones can be relevant not only for the genesis and / or maintenance of altered dietary behaviors, but also for the development of specific psychopathological aspects in eating disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Second cancers in patients with neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Hui-Jen Tsai

    Full Text Available BACKGROUND: Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs. However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR to analyze the incidence and distribution of second cancers after the diagnosis of NETs. METHODS: NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR and 95% confidence interval (CI for the risk of second cancers associated with sex, age, and primary NET sites. RESULTS: A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63% developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96, especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22. There appeared to be no preference of second cancer type according to the primary sites of NETs. CONCLUSIONS: Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted.

  12. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.

    Science.gov (United States)

    Park, Hyeong-Kyu; Ahima, Rexford S

    2015-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Neuroendocrine Adenoma of the Middle Ear: A Rare Histopathological Diagnosis

    Directory of Open Access Journals (Sweden)

    Zubair Hasan

    2016-01-01

    Full Text Available Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours.

  14. Nasal neuroendocrine carcinoma in a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus).

    Science.gov (United States)

    Kubo, M; Matsuo, Y; Okano, T; Sakai, H; Masegi, T; Asano, M; Uchida, K; Yanai, T

    2009-01-01

    Neuroendocrine carcinoma was diagnosed in the left nasal cavity of a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus). Microscopically, the tumour consisted of sheets of anaplastic cells separated by narrow zones of fibrovascular stroma. The neoplastic cells had varying numbers of cytoplasmic granules stained by the Grimelius method. Immunohistochemically, the neoplastic cells were variably labelled for cytokeratin AE1/AE3, vimentin, chromogranin A and S-100. Ultrastructurally, some of the neoplastic cells had cytoplasmic membrane-bound dense-core granules of approximate diameter 140-240nm. The tumour had infiltrated the cerebrum and metastasized to the pituitary gland, mandibular and pulmonary lymph nodes, lungs, thyroid gland and adrenal glands.

  15. Neuroendocrine tumor liver metastases treated with yttrium-90 radioembolization.

    Science.gov (United States)

    Fan, Katherine Y; Wild, Aaron T; Halappa, Vivek G; Kumar, Rachit; Ellsworth, Susannah; Ziegler, Mark; Garg, Tanu; Rosati, Lauren M; Su, Zheng; Hacker-Prietz, Amy; Pawlik, Timothy M; Cosgrove, David P; Hong, Kelvin K; Kamel, Ihab R; Geschwind, Jean-Francois; Herman, Joseph M

    2016-09-01

    Yttrium-90 (Y-90) radioembolization is an emerging treatment option for unresectable neuroendocrine liver metastases (NELM). However, the data regarding this treatment are currently limited. This study evaluates the efficacy and tolerability of Y-90 radioembolization and identifies prognostic factors for radiographic response and survival. Thirty-eight patients underwent Y-90 radioembolization for NELM at our institution between April 2004 and February 2012. Patients were assessed radiographically (RECIST criteria, enhancement), serologically, and clinically at 1month, and then at every 3months after treatment for tumor response, toxicity, and survival outcomes. Median length of follow-up was 17.0months (IQR, 9.0-37.0). Median survival was 29.2months. Three patients (9%) had a radiographic complete response to treatment, 6 (17%) had a partial response, 21 (60%) had stable disease, and 5 (14%) developed progressive disease. Two factors were significantly associated with a good radiographic response (complete/partial response): islet cell histological subtype (p=0.043) and hepatic tumor burden ≥33% (p=0.031). Multivariate analysis revealed that patients requiring multiple Y-90 treatments (HR 2.9, p=0.035) and patients who had previously failed systemic therapy with octreotide/chemotherapy (HR 4.4, p=0.012) had worse survival. Grade 3 serologic toxicity was observed in 2 patients (5%; hyperbilirubinemia, elevated alkaline phosphatase) after treatment. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). No grade 4 or 5 toxicity was reported. Y-90 radioembolization is a promising treatment option for inoperable NELM and is associated with low rates of grade≥3 toxicity. Copyright © 2016. Published by Elsevier Inc.

  16. A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit

    Science.gov (United States)

    Turaka, Kiran; Mashayekhi, Arman; Shields, Carol L.; Lally, Sara E.; Kligman, Brad; Shields, Jerry A.

    2011-01-01

    Purpose/Background: To report the clinical and radiographic features and treatment outcome of neuroendocrine tumor (carcinoid) metastasis to the orbit. Materials and Methods: Retrospective chart review of four cases. Results: Mean patient age at the time of diagnosis of the primary neuroendocrine tumor and orbital metastasis was 58 and 66 years, respectively, with a mean duration of 8 years between diagnosis of primary tumor and orbital metastasis. Primary neuroendocrine tumor sites were gastrointestinal tract (n = 2), lung (n = 1), and testicle (n = 1). The most common presenting symptom was diplopia (three cases). Magnetic resonance imaging revealed orbital tumor in all cases. Octreotide scan was positive in one case. Treatment was tumor excision in three cases followed by external beam radiotherapy in two cases and one patient was followed without treatment. Tumor cells showed immunoreactivity to chromogranin, synaptophysin, and neuron-specific enolase in all cases. Mean follow-up after orbital tumor diagnosis was 39 months. Three patients had known systemic extraorbital metastasis before orbital involvement (mean interval of 5.9 years) and one case had immediately after development of orbital metastasis. One patient had multiple recurrences of orbital metastasis and eventually underwent exenteration. Two patients died of disseminated metastasis between 2 and 3 years after diagnosis of orbital metastasis. Conclusion: All four patients with orbital metastasis from neuroendocine tumor had evidence of systemic extraorbital metastasis. Aggressive metastatic neuroendocine tumors of orbit can lead to local recurrence even after surgical excision and radiation. Imaging tests were helpful in allowing early diagnosis and for monitoring after treatment. PMID:22279400

  17. Peptide receptor radionuclide therapy of neuroendocrine tumours; Traitement des tumeurs neuro-endocrines par les peptides radiomarques

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Nuclear Medicine Div., Milan (Italy); Giammarile, F. [Centre hospitalier Lyon-Sud, EA 3738, HCL, UCBL, 69 - Pierre-Benite (France)

    2009-02-15

    Neuroendocrine tumours are considered relatively rare tumours that have the characteristic property of secreting bioactive substances, such as amines and hormones. They constitute a heterogeneous group, characterized by good prognosis, but important disparities of the evolutionary potential. In the aggressive forms, the therapeutic strategies are limited. The metabolic or internal radiotherapy, using radiolabelled peptides, which can act at the same time on the primary tumour and its metastases, constitutes a tempting therapeutic alternative, currently in evolution. The prospects are related to the development of new radiopharmaceuticals, with the use of other peptide analogues whose applications will overflow the framework of the neuro-endocrine tumours. (authors)

  18. Cross-talk among immune and neuroendocrine systems in molluscs and other invertebrate models.

    Science.gov (United States)

    Malagoli, Davide; Ottaviani, Enzo

    2017-02-01

    The comparison between immune and neuroendocrine systems in vertebrates and invertebrates suggest an ancient origin and a high degree of conservation for the mechanisms underlying the integration between immune and stress responses. This suggests that in both vertebrates and invertebrates the stress response involves the integrated network of soluble mediators (e.g., neurotransmitters, hormones and cytokines) and cell functions (e.g., chemotaxis and phagocytosis), that interact with a common objective, i.e., the maintenance of body homeostasis. During evolution, several changes observed in the stress response of more complex taxa could be the result of new roles of ancestral molecules, such as ancient immune mediators may have been recruited as neurotransmitters and hormones, or vice versa. We review older and recent evidence suggesting that immune and neuro-endocrine functions during the stress response were deeply intertwined already at the dawn of multicellular organisms. These observations found relevant reflections in the demonstration that immune cells can transdifferentiate in olfactory neurons in crayfish and the recently re-proposed neural transdifferentiation in humans. Copyright © 2016. Published by Elsevier Inc.

  19. Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

    Directory of Open Access Journals (Sweden)

    Susanne Grässel

    2018-01-01

    Full Text Available Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH, adrenocorticotropin (ACTH and β-endorphin (β-ED, and sympathetic neuropeptides like vasoactive intestinal peptide (VIP and neuropeptide y (NPY. Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs. In particular, α-MSH, ACTH and specific melanocortin-receptor (MCR agonists appear to have promising anti-inflammatory actions demonstrated in animal models of experimentally induced arthritis and osteoarthritis (OA. Sympathetic neuropeptides have obtained increasing attention as they have crucial trophic effects that are critical for joint tissue and bone homeostasis. VIP and NPY are implicated in direct and indirect activation of several anabolic signaling pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase-activating polypeptide (PACAP proved to be chondroprotective and, thus, might be a novel target in OA. Taken together, it appears more and more likely that the anabolic effects of these neuroendocrine peptides or their respective receptor agonists/antagonists may be exploited for the treatment of patients with inflammatory and degenerative joint diseases in the future.

  20. A Novel Case of Functional Gastric Neuroendocrine Carcinoma Occurred after Endoscopic Submucosal Dissection

    Directory of Open Access Journals (Sweden)

    Yoshiaki Shibata

    2013-01-01

    Full Text Available In Japan, endoscopic submucosal dissection (ESD is becoming a standard treatment for intramucosal differentiated gastric cancer. Although ESD is associated with a high cure rate for patients with early gastric cancer, tumors may recur, albeit rarely. We performed ESD on an 80-year-old man with a small depressed type of gastric cancer of the posterior wall of the cardia, found to be locally invasive on histology. Thirty months later, local recurrence and multiple liver metastases were detected, accompanied by frequent severe hypoglycemia. Despite chemotherapy, the patient died 6 months after relapse. On autopsy, the recurrent gastric lesion and liver metastases were examined immunohistochemically. Several characteristic tumor cells were positive for chromogranin A, cluster of differentiation (CD 56, Ki-67, and insulin-like growth factor (IGF-II. Western blot analysis of the patient’s serum obtained during a hypoglycemic attack showed the high molecular weight form of IGF-II or “big” IGF-II. The patient was diagnosed with non-islet cell tumor hypoglycemia (NICTH, with “big” IGF-II being produced by the gastric neuroendocrine carcinoma. This is the novel case of a functional gastric neuroendocrine carcinoma that occurred after ESD and induced a hypoglycemic attack associated with NICTH.

  1. Neuroendocrine tumors of the lung: major radiologic findings in a series of 22 histopathologically confirmed cases

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam, E-mail: marcelk46@yahoo.com.br [Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP), SP (Brazil); Department of Diagnostic and Interventional Radiology, Heidelberg University (Germany); Barreto, Andre Rodrigues Facanha [Clinica Radius, Clinica Sao Carlos Imagem and Santa Casa de Misericordia de Fortaleza, Fortaleza, CE (Brazil); Chagas Neto, Francisco Abaete [Program of Health Sciences Applied to the Locomotor System - Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, SP (Brazil); Muglia, Valdair Francisco; Elias Junior, Jorge [Division of Radiology, Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRPUSP), Ribeirao Preto, SP (Brazil)

    2012-07-15

    Objective: To describe key imaging findings in a series of cases of primary neuroendocrine tumors of the lung (NTLs), with emphasis on computed tomography changes. Materials And Methods: Imaging studies of 22 patients (12 men, mean age 60 years) with histopathologically confirmed diagnosis, evaluated in the author's institution during the last five years were retrospectively reviewed by two radiologists, with findings being consensually described focusing on changes observed at computed tomography. Results: The authors have described five typical carcinoids, three atypical carcinoids, three large-cell neuroendocrine carcinomas (LCNCs), and 11 small-cell lung cancers (SCLCs). Only one typical carcinoid presented the characteristic appearance of central endobronchial nodule with distal pulmonary atelectasis, while the others were pulmonary nodules or masses. The atypical carcinoids corresponded to peripheral heterogeneous masses. One out of the three LCNCs was a peripheral homogeneous mass, while the others were ill-defined and heterogeneous. The 11 SCLCs corresponded to central, infiltrating and heterogeneous masses with secondary pleuropulmonary changes. Calcifications were absent both in LGNCs and SCLCs. Metastases were found initially and also at follow-up of all the cases of LCNCs and SCLCs. Conclusion: Although some imaging features may be similar, radiologic findings considered together with clinical information may play a relevant role in the differentiation of histological types of NTLs. (author)

  2. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors.

    Science.gov (United States)

    Dralle, Henning; Krohn, Sabine L; Karges, Wolfram; Boehm, Bernhard O; Brauckhoff, Michael; Gimm, Oliver

    2004-12-01

    Nonfunctioning neuroendocrine pancreatic tumors (NFNEPTs) comprise about one-third of pancreatic endocrine tumors. Based on immunohistochemistry, nonfunctioning tumors are difficult to distinguish from functioning ones; therefore the final diagnosis is basically the result of a synopsis of pathology and clinical data. Owing to their incapacity to produce hormone-dependent symptoms, NFNEPTs are detected incidentally or because of uncharacteristic symptoms resulting from local or distant growth. About two-thirds of NFNEPTs are located in the pancreatic head, so jaundice may be a late symptom of this tumor. Modern diagnostic procedures are best applied by a stepwise approach: first endoscopic ultrasonography and computed tomography/magnetic resonance imaging followed by somatostatin receptor scintigraphy or positron emission tomography (or both). Due to significant false-positive and false-negative findings, for decision-making the latter should be confirmed by a second imaging modality. Regarding indications for surgery and the surgical approach to the pancreas, three pancreatic manifestations of NFNEPTs can be distinguished: (1) solitary benign non-multiple endocrine neoplasia type 1 (non-MEN-1); (2) multiple benign MEN-1; and (3) malignant NFNEPTs. Reviewing the literature and including our experience with 18 NFNEPTs (8 benign, 10 malignant) reported here, the following conclusions can be drawn: (1) Solitary benign non-MEN-1 NFNEPTs can be removed by enucleation or by pancreas-, spleen-, and duodenum-preserving techniques in most cases. The choice of surgical technique depends on the location and site of the tumor and its anatomic relation to the pancreatic duct. (2) With multiple benign MEN-1 NFNEPTs, because of the characteristics of the underlying disease a preferred, more conservative concept (removal of only macrolesions) competes with a more radical procedure (left pancreatic resection with enucleation of head macrolesions). Further studies are necessary to

  3. Primary neuroendocrine carcinoma of breast: a rare case report ...

    African Journals Online (AJOL)

    Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due its rare incidence and lack of definitive criteria for diagnosis. We present a case of PNEC of breast in a middle aged lady. A 34 years lady presented with a breast lump since 1 month, who underwent modified radical ...

  4. Sexual differentiation and the neuroendocrine hypothesis of autism.

    Science.gov (United States)

    Aiello, Timothy P; Whitaker-Azmitia, Patricia M

    2011-10-01

    The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphic-the amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-β estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Copyright © 2011 Wiley-Liss, Inc.

  5. Neuroendocrine Tumour in a Patient with Neurofibromatosis Type 1 ...

    African Journals Online (AJOL)

    We report the case of an HIV-positive female patient with neurofibromatosis type 1 who was treated for recurrent peptic ulcer disease and later developed diabetes mellitus and chronic diarrhoea. A metastasising somatostatinoma was histologically proven and evidence of a concomitant gastrin-producing neuroendocrine ...

  6. Neuroendocrine differentiation in a case of cervical cancer | Rashed ...

    African Journals Online (AJOL)

    Neuroendocrine neoplasms may occur in the uterine cervix, although rarely; it accounts for 0.5-1% of all malignant tumors of the uterine cervix. A case report of an Ethiopian female presented at the Gynecology Out-Patient Clinic at Jimma University Hospital, complaining from irregular vaginal bleeding over the previous ...

  7. Capnocytophaga Lung Abscess in a Patient with Metastatic Neuroendocrine Tumor

    OpenAIRE

    Thirumala, Raghu; Rappo, Urania; Babady, N. Esther; Kamboj, Mini; Chawla, Mohit

    2012-01-01

    Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor.

  8. Capnocytophaga lung abscess in a patient with metastatic neuroendocrine tumor.

    Science.gov (United States)

    Thirumala, Raghu; Rappo, Urania; Babady, N Esther; Kamboj, Mini; Chawla, Mohit

    2012-01-01

    Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor.

  9. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  10. Fish caudal neurosecretory system: a model for the study of neuroendocrine secretion.

    Science.gov (United States)

    McCrohan, Catherine R; Lu, Weiqun; Brierley, Matthew J; Dow, Louise; Balment, Richard J

    2007-01-01

    The caudal neurosecretory system (CNSS) is unique to fish and has suggested homeostatic roles in osmoregulation and reproduction. Magnocellular neuroendocrine Dahlgren cells, located in the terminal segments of the spinal cord, project to a neurohaemal organ, the urophysis, from which neuropeptides are released. In the euryhaline flounder Platichthys flesus Dahlgren cells synthesise at least four peptides, including urotensins I and II and CRF. These peptides are differentially expressed with co-localisation of up to three in a single cell. Dahlgren cells display a range of electrical firing patterns, including characteristic bursting activity, which is dependent on L-type Ca(2+) and Ca-activated K(+)channels. Activity is modulated by a range of extrinsic and intrinsic neuromodulators. This includes autoregulation by the secreted peptides themselves, leading to enhanced bursting. Electrophysiological and mRNA expression studies have examined changes in response to altered physiological demands. Bursting activity is more robust and more Dahlgren cells are recruited in seawater compared to freshwater adapted fish and this is mirrored by a reduction in mRNA expression for L-type Ca(2+) and Ca-activated K(+) channels. Acute seawater/freshwater transfer experiments support a role for UII in adaptation to hyperosmotic conditions. Responses to stress suggest a shared role for CRF and UI, released from the CNSS. We hypothesise that the Dahlgren cell population is reprogrammed, both in anticipation of and in response to changed physiological demands, and this is seen as changes in gene expression profile and electrical activity. The CNSS shows striking parallels with the hypothalamic-neurohypophysial system, providing a highly accessible system for studies of neuroendocrine mechanisms. Furthermore, the presence of homologues of urotensins throughout the vertebrates has sparked new interest in these peptides and their functional evolution.

  11. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report

    Directory of Open Access Journals (Sweden)

    Nicolas M. Orsi

    2016-08-01

    Full Text Available Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10–12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade, arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area.

  12. Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin.

    Science.gov (United States)

    Horowitz, Mark A; Zunszain, Patricia A

    2015-09-01

    Major depressive disorder has been linked to alterations in several interacting systems, particularly with respect to neuroendocrine and neuroinflammatory dysfunction. Increased levels of both cortisol and proinflammatory cytokines have regularly been described. This presents an apparent paradox, given the well-known anti-inflammatory properties of glucocorticoids, including inhibition of cytokine release. There are two competing theories to resolve this paradox: one proposes that reduced glucocorticoid signaling, as a result of glucocorticoid resistance, creates a permissive environment for an overactive innate immune system; the other theory focuses on evidence that glucocorticoids can be proinflammatory under some circumstances, depending on context and temporal factors. This review assesses the evidence base and limitations of both theories, discussing animal and clinical data, and preliminary work in human neural cells. Further work to delineate the relationship between neuroimmune and neuroendocrine systems in depression will be critical for understanding the biological perturbations underpinning depression, and therefore, for discerning treatment targets, and we include suggestions for future directions. © 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  13. Role of the endocannabinoid system in the neuroendocrine responses to inflammation.

    Science.gov (United States)

    De Laurentiis, Andrea; Araujo, Hugo A; Rettori, Valeria

    2014-01-01

    A few years ago the endocannabinoid system has been recognized as a major neuromodulatory system whose main functions are to exert and maintain the body homeostasis. Several different endocannabinoids are synthesized in a broad class of cell types, including those in the brain and the immune system; they bind to cannabinoid G-protein-coupled receptors, having profound effects on a variety of behavioral, neuroendocrine and autonomic functions. The coordinated neural, immune, behavioral and endocrine responses to inflammation are orchestrated to provide an important defense against infections and help homeostasis restoration in the body. These responses are executed and controlled mainly by the hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal system is essential for survival and plays a role recovering the homeostasis under a variety of stress conditions, including inflammation and infection. Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions. In the present review we focused on the endocannabinoids actions on the neuroendocrine response to inflammation and infection. We provide a detailed overview of the current understanding of the role of the endocannabinoid system in the recovering of homeostasis as well as potential pharmacological therapies based on the manipulation of endocannabinoid system components that could provide novel treatments for a wide range of disorders.

  14. Antiphase signalling in the neuroendocrine-immune system in healthy humans.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Muscarella, Lucia Anna; Fazio, Vito Michele; Piepoli, Ada; Pazienza, Valerio; Dagostino, Mariangela Pia; Giuliani, Francesco; Polyakova, Victoria O; Kvetnoy, Igor

    2011-07-01

    Any quantity varying in the spatial-temporal dimension may be considered as a signal. Human lymphocyte cell surface molecules and subsets present circadian variation and this variation may represent a kind of signalling in the neuroendocrine-immune system. We have analyzed the dynamics of variation of specific lymphocyte subsets in healthy humans. In our study, lymphocyte subpopulation analyses were performed and cortisol, melatonin, GH and TSH serum levels were measured on blood samples collected every 4h for 24 hours from eleven healthy men, ages 35-53 years (mean=44±6SD). A clear circadian rhythm was validated for CD8 and cortisol with acrophase during the day and for CD3, CD4, melatonin, GH and TSH with acrophase at night. Cross-correlation showed that CD3 correlated positively with CD4 (ρ=0.67, Pneuroendocrine hormones and might represent a way of signal transmission among the multiple components of the neuroendocrine-immune system. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

    Directory of Open Access Journals (Sweden)

    McAleese Jonathan

    2007-07-01

    Full Text Available Abstract Background Neuroendocrine tumours (NET are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare. Case presentation We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on 123I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy. Conclusion These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.

  16. Missing and Possible Link between Neuroendocrine factors, Neuropsychiatric Disorders and Microglia

    Directory of Open Access Journals (Sweden)

    Takahiro A. Kato

    2013-07-01

    Full Text Available Endocrine systems have long been suggested to be on of the important factors in neuropsychiatric disorders, while the underlying mechanisms have not been well understood. Traditionally, neuropsychiatric disorders have been mainly considered the consequence of abnormal conditions in neural circuitry. Beyond the neuronal doctrine, microglia, one of the glial cells with inflammatory/immunological functions in the CNS, have recently been suggested to play important roles in neuropsychiatric disorders. However, the crosstalk between neuroendocrine factors, neuropsychiatric disorders and microglia has been unsolved. Therefore, we herein introduce and discuss a missing and possible link between these three factors; especially highlighting the following hormones; (1 Hypothalamic-Pituitary-Adrenal (HPA axis-related hormones such as corticotropin-releasing hormone (CRH and glucocorticoids, (2 sex-related hormones such as estrogen and progesterone, and (3 oxytocin. A growing body of evidence has suggested that these hormones have a direct effect on microglia. We hypothesize that hormone-induced microglial activation and the following microglia-derived mediators may lead to maladaptive neuronal networks including synaptic dysfunctions, causing neuropsychiatric disorders. Future investigations to clarify the correlation between neuroendocrine factors and microglia may contribute to a novel understanding of the pathophysiology of neuropsychiatric disorders.

  17. Salvage treatment after r-interferon α-2a in advanced neuroendocrine tumors

    International Nuclear Information System (INIS)

    Zilembo, N.; Buzzoni, R.; Bajetta, E.; Di Bartolomeo, M.; De Braud, F.; Castellani, R.; Maffioli, L.; Celio, L.; Villa, E.; Lorusso, V.; Fosser, V.; Buzzi, F.

    1993-01-01

    The use of interferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN α-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIBG uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m 2 intravenously days 1, 2, 3 and epirubicin 75 mg/m 2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective. (orig.)

  18. The gsp oncogene disrupts Ras/ERK-dependent prolactin gene regulation in gsp inducible somatotroph cell line.

    Science.gov (United States)

    Pertuit, M; Romano, D; Zeiller, C; Barlier, A; Enjalbert, A; Gerard, C

    2011-04-01

    The MAPK ERK1/2 cascade regulates all the critical cellular functions, and in many pathological situations, these regulatory processes are perturbed. It has been clearly established that this cascade is an integrative point in the control of the pituitary functions exerted by various extracellular signals. In particular, ERK1/2 cross talk with the cAMP pathway is determinant in the control of somatolactotroph hormonal secretion exerted via neuropeptide receptors. GH-secreting adenomas are characterized by frequent cAMP pathway alterations, such as constitutive activation of the α-subunit of the heterotrimeric Gs protein (the gsp oncogene), overexpression of Gsα, and changes in the protein kinase A regulatory subunits. However, it has not yet been established exactly how these alterations result in GH-secreting adenomas or how the ERK1/2 cascade contributes to the process of GH-secreting adenoma tumorigenesis. In this study on the conditional gsp-oncogene-expressing GH4C1 cell line, expression of the gsp oncogene, which was observed in up to 40% of GH-secreting adenomas, was found to induce sustained ERK1/2 activation, which required activation of the protein kinase A and the GTPases Ras and Rap1. All these signaling components contribute to the chronic activation of the human prolactin promoter. The data obtained here show that Ras plays a crucial role in these processes: in a physiopathological context, i.e. in the presence of the gsp oncogene, it switched from being a repressor of the cAMP/ protein kinase A ERK-sensitive prolactin gene control exerted by neuropeptides to an activator of the prolactin promoter.

  19. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury.

    Science.gov (United States)

    Zihl, Josef; Almeida, Osborne F X

    2015-05-20

    Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  20. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Josef Zihl

    2015-05-01

    Full Text Available Endocrine dysfunction is a common effect of traumatic brain injury (TBI. In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  1. [The behavioral-neuroendocrine mechanism of development of homosexuality].

    Science.gov (United States)

    Xue, Hui; Tai, Fa-Dao

    2007-10-01

    In this review, we primarily focus on the behavioral-neuroendocrine mechanism of development of homosexuality from genetic, neuroendocrine neuroanatomical and behavioral studies. Besides the influence of genetics and environment, sexual orientation was determined by the early perinatal hormone exposure. Gonadal steroidal hormone interacted with many neurotransmitters in individual development by hypothalamus pituitary adrenal axis and hypothalamus pituitary gonadal axis, which regulated the individual's sexual orientation. It was summarized here about the future directions on sexual orientation and demonstrated problems which would have to investigate next step. All these may be beneficial for our understanding of the homosexuality and paying attention to psychological and physiological health of homosexuality, which is useful to prevent the development of teenage homosexuality.

  2. Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.

  3. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    OpenAIRE

    Zihl, J.; Almeida, O.

    2015-01-01

    Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental f...

  4. Peptide Receptor Radionuclide Therapy in the Treatment of Neuroendocrine Tumors.

    Science.gov (United States)

    Kwekkeboom, Dik J; Krenning, Eric P

    2016-02-01

    Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors patients. Most studies report objective response rates in 15% to 35% of patients. Progression-free (PFS) and overall survival (OS) compare favorably with that for somatostatin analogues, chemotherapy, or newer, "targeted" therapies. Prospective, randomized data regarding the potential PFS and OS benefit of PRRT compared with standard therapies is anticipated. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  6. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    Directory of Open Access Journals (Sweden)

    Arpad eDobolyi

    2012-10-01

    Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control

  7. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dilemmas in Endoscopic Management of Rectal Neuroendocrine Tumors: A Case-Based Discussion

    Directory of Open Access Journals (Sweden)

    Brian P. Rajca

    2015-01-01

    Full Text Available Rectal neuroendocrine tumors are uncommon neoplasms that historically were regarded as having an indolent course. Due to the widespread use of screening colonoscopy neuroendocrine tumors of the rectum are identified with increasing frequency. More recent literature has suggested that rectal neuroendocrine tumors may progress in a more malignant fashion than previously believed. In this case-based discussion we present management dilemmas, analyze current guidelines, and highlight the role of endoscopic ultrasound, endoscopic resection, and surgery.

  9. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  10. Neuroendocrine mechanisms for immune system regulation during stress in fish.

    Science.gov (United States)

    Nardocci, Gino; Navarro, Cristina; Cortés, Paula P; Imarai, Mónica; Montoya, Margarita; Valenzuela, Beatriz; Jara, Pablo; Acuña-Castillo, Claudio; Fernández, Ricardo

    2014-10-01

    In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Neuroendocrine brake for the treatment of morbid obesity. Preliminary report

    Directory of Open Access Journals (Sweden)

    Aureo Ludovico de Paula

    2005-06-01

    Full Text Available Objectives: To demonstrate the preliminary results of a newtechnique named neuroendocrine brake, for surgical treatment ofmorbid obesity. Methods: In November 2003, three patientsunderwent the neuroendocrine brake operation performed by thelaparoscopic approach. The mean age was 46.4 years; all patientswere female. Mean BMI was 42.3 kg/m2. The patients selectedpresented some relative or absolute contraindications to the useof gastrointestinal bypass techniques, including gastric ulcer anda family history of gastric malignancy(1 and chronic anemia (2.All patients had associated diseases, including type II diabetesmellitus (2, hypertension (2, obstructive sleep apnea (1,dyslipidemia (3, cholecystolithiasis (1, gastric ulcer (1 andchronic anemia (2. The laparoscopic technique consisted of anileal interposition at the proximal jejunum and longitudinalgastrectomy. Results: There was no conversion to open surgery orpostoperative complications. Sixteen months later, the meanpercentage of initial body weight loss was 44.6% and the meanBMI was 24.3 kg/m2. Glucose, triglyceride and cholesterol levelswere normalized, and sleep apnea showed remission. Conclusion:In spite of the reduced number of patients and short term followup, the good results suggest that the neuroendocrine brake maybecome an option for surgical treatment of morbid obesity in thenear future.

  12. Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells

    International Nuclear Information System (INIS)

    Colturato, Maria Tereza

    2005-01-01

    mixture (simple purification) and to produce the radiopharmaceutical with high specific activity (complex purification and HPLC), were both efficient in the separation of the species in the reaction mixtures, as demonstrated by quality control procedures. Biological distribution studies were accomplished by venous administration of the radiopharmaceuticals in laboratory animals: biodistribution study of [ 131 I]VIP and [ 131 I]VIP 10-28 in normal Swiss mice, [ 131 I]VIP not purified and purified in Swiss mice with tumor and [ 131 I]VIP and [ 131 I]VIP 10-28 in Nude mice with tumor, scintigraphic images of [ 131/123 I]VIP and [ 123 I]VIP 10-28 in Swiss and Nude mice and Wistar rats with tumor. In vitro studies were accomplished to determine the percentage of [ 131 I]VIP and [ 131 I]VIP 10-28 bound to plasmatic proteins, stability study of [ 131 I]VIP and [ 131 I]VIP 10-28 in human plasma and the affinity and internalization of [ 131 I]VIP and [ 131 I]VIP 10-28 by tumour adenocarcinoma cells of human rectal colon (HT-29). All biological distribution studies demonstrated that both [ 131/123 I]VIP and [ 131/123 I]VIP 10-28 showed fast blood clearance, low renal and liver uptake, relative uptake in thyroid, showing in vivo dehalogenation and good uptake in tumour. Comparative biological distribution of the radiopharmaceuticals showed high uptake in the stomach for both peptides. The blood clearance of the fragment was slower, and influences the visualization of the tumour mass. The radiopharmaceuticals, [ 123 I]VIP and [ 123 I]VIP 10-28, were obtained with high radiochemical purity, but with low radiochemical yield when comparing with labeling procedures using iodine-131. Quality control assays of [ 123 I]Na indicated that the presence of radiochemical and radionuclide impurities influenced on labeling results. (author)

  13. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

    Meltzer, H Y; Fang, V S; Tricou, B J; Robertson, A

    1982-01-01

    Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors

  14. [Neuropeptides, Cytokines and Thymus Peptides as Effectors of Interactions Between Thymus and Neuroendocrine System].

    Science.gov (United States)

    Torkhovskaya, T I; Belova, O V; Zimina, I V; Kryuchkova, A V; Moskvina, S N; Bystrova, O V; Arion, V Ya; Sergienko, V I

    2015-01-01

    The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The pres- ence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymuspeptides and/or cytokines, controlled by them, enter the brain and exert influence on neuro- nalfunction, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.

  15. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Rehfeld, Anders Aagaard; Plass, Mireya; Døssing, Kristina

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site...... and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire...... and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions...

  16. Neuroendocrine tumor in the lung of a captive black spider monkey (Ateles paniscus).

    Science.gov (United States)

    Cho, Ho-Seong; Kim, Yeong-Seob; Choi, Chan; Lee, Jae-Hyuk; Kurkure, Nitin V; Subramanian, Madhan; Park, Nam-Yong

    2007-07-01

    This paper describes a neuroendocrine (NE) tumor of the lung that was observed during the necropsy of a 14-year-old female black spider monkey (Ateles paniscus) with sudden death. Grossly, multifocal firm and coalescing nodular masses were observed in the lung. The histological examination showed the tumor to be an typical NE tumor with polygonal cells grouped in small solid aggregates, with regularly sized, spherical, centrally placed nuclei with modest, lightly granular cytoplasm suspended in a fibrovascular stroma. The immunohistochemical examination revealed the tumor to be positive for cytokeratin, chromogranin A and synaptophysin, and negative for CD56. To the best of our knowledge, this is the first report of NE tumor in the lung of the black spider monkey.

  17. Mash1 expression is induced in neuroendocrine prostate cancer upon the loss of Foxa2.

    Science.gov (United States)

    Gupta, Aparna; Yu, Xiuping; Case, Tom; Paul, Manik; Shen, Michael M; Kaestner, Klaus H; Matusik, Robert J

    2013-05-01

    Neuroendocrine (NE) prostate tumors and neuroendocrine differentiation (NED) in prostatic adenocarcinomas have been associated with poor prognosis. In this study, we used the TRAMP mouse model that develops NE prostate tumors to identify key factors that can lead to NED. We have previously reported that NE tumors express the forkhead transcription factor, Foxa2, Mash1 (mouse achaete scute homolog-1), as well as Synaptophysin. In TRAMP, the prostatic intraepithelial neoplasia (PIN) first expresses Foxa2 and Synaptophysin, which then progresses to NE cancer. In order to determine if Foxa2 is dispensable for development or maintenance of NE cancer, a conditional knock-out of Foxa2 in TRAMP mice was generated by breeding mice with two floxed alleles of Foxa2 and one copy of Nkx3.1-Cre. Nkx3.1-Cre/Foxa2(loxP/loxP) mice showed loss of Foxa2 expression in embryonic prostatic buds. No expression of Foxa2 was seen in the adult prostate in either conditional null or control mice. Foxa2 is universally expressed in all wild type TRAMP NE tumors, but Mash1 expression is seen only in a few samples in a few cells. With the loss of Foxa2 in the NE tumors of the TRAMP/Nkx3.1-Cre/Foxa2(loxP/loxP) mice, the expression of the pro-neuronal gene Mash1 is upregulated. NE tumors from both the TRAMP control and Foxa2-deficient TRAMP prostate express Synaptophysin and SV40 Large T-antigen, and both show a loss of androgen receptor expression in NE cells. These studies suggest that the TRAMP NE tumors can form in the absence of Foxa2 by an up regulation of Mash1. Copyright © 2012 Wiley Periodicals, Inc.

  18. Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system.

    Science.gov (United States)

    Slominski, Andrzej T; Zmijewski, Michal A; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M; Steketee, Jeffery D

    2012-01-01

    Skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, integrates, and responds to a diverse range of stressors including solar radiation. It has already been established that the skin is an important peripheral neuro-endocrine-immune organ that is tightly networked to central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides, and hormones. Such production is stimulated by ultraviolet radiation (UVR), biological factors (infectious and noninfectious), and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin, and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, beta-endorphin or MSH peptides, thyroid-stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7-delta steroids), secosteroids, opioids, and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as hypothalamic-pituitary-adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid, and endocannbinoid systems. Dysregulation of these axes or of communication between them may lead to skin and/ or systemic diseases. These local neuroendocrine networks are also addressed at restricting maximally the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve

  19. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  20. Neuroendocrine, Autonomic, and Metabolic Responses to an Orexin Antagonist, Suvorexant, in Psychiatric Patients with Insomnia.

    Science.gov (United States)

    Nakamura, Masaru; Nagamine, Takahiko

    2017-01-01

    Aim: The aim of this study was to investigate the neuroendocrine, autonomic, and metabolic system responses to suvorexant in psychiatric subjects with insomnia. Design: This prospective study was conducted in Kusatsu Hospital in Hiroshima, Japan and included 40 psychiatric inpatients treated with suvorexant from December 2014 to April 2016. Methods: Questionnaire of Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scores were checked at baseline, Week 2, and Week 4, and fasting serum levels of prolactin, insulin, cortisol, noradrenaline, white blood cell count, and average pulse rate were measured at baseline and Week 4 and Week 8 after suvorexant initiation. Sequential change of the values were compared against baseline respectively. Results: Subjective sleep quality scores were significantly decreased at Weeks 2 and 4, and sleep duration, habitual sleep efficacy, and global scores were significantly decreased at Week 4 from baseline. Total scores on the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-9 significantly decreased at Week 4 from baseline. The levels of cortisol and white blood cell count were decreased, significantly at Week 8, and the levels of pulse rate were significantly decreased at Week 4 from baseline. The levels of noradrenaline decreased, although not significantly. The prolactin levels remained unchanged, and no trend was found in the insulin levels. Conclusion: Suvorexant treatment resulted in overall improvement in the quality of sleep and the severity of anxiety and depression. This dual orexin antagonist may be related to autonomic functions and neuroendocrine systems, especially in the hypothalamus-pituitary-adrenal axis in psychiatric subjects.

  1. WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Eric Johannesen

    2014-01-01

    Full Text Available Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

  2. Large-cell neuroendocrine carcinoma of the uterine cervix- a ...

    African Journals Online (AJOL)

    On histopathological examination, all 5 tumours showed features of a high-grade poorly differentiated malignant neoplasm with ulceration and extensive tumour necrosis including trabecular and organoid growth patterns. All 5 neoplasms also showed strong immunoreactivity for MNF116, while their endocrine nature was ...

  3. The Function of Neuroendocrine Cells in Prostate Cancer

    Science.gov (United States)

    2013-04-01

    posi- tion of lysine of the target protein. Unlike ubiquitin modifi- cation, the main function of sumoylation is not a signal of destruction of the... antagonize ubiq- uitination through competitive modification (21–23). Another difference between ubiquitination and sumoylation is their respective core...in a decreased p53 level. It has been shown that a mutant SKI with an insertion of four amino acids, alanine, arginine , proline, and glycine (ARPG

  4. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    Science.gov (United States)

    ... a non-functional pancreatic NET. Abdominal CT scan (CAT scan) : A procedure that makes a series of ... called octreotide scan and SRS. Insulinoma Fasting serum glucose and insulin test : A test in which a ...

  5. Treatment Option Overview (Pancreatic Neuroendocrine Tumors / Islet Cell Tumors)

    Science.gov (United States)

    ... This is also called the Whipple procedure . Distal pancreatectomy : Surgery to remove the body and tail of ... of the pancreas, treatment is usually a distal pancreatectomy (surgery to remove the body and tail of ...

  6. Temozolomide as second or third line treatment of patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Sørensen, Jens B; Federspiel, Birgitte

    2012-01-01

    Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results.......Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results....

  7. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

    DEFF Research Database (Denmark)

    Janson, Eva Tiensuu; Sorbye, Halfdan; Welin, Staffan

    2014-01-01

    BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine...

  8. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    Directory of Open Access Journals (Sweden)

    Rita Azeredo

    2017-09-01

    Full Text Available Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level or a control diet meeting the amino acids requirement levels (CTRL. Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected with the bacteria inoculum but only compared to those fed MET. However, no changes were detected in total antioxidant capacity. Complement factor 3 was upregulated in MET-fed fish but methionine seemed to poorly affect other genes expression patterns. In contrast, fish fed MET showed increased immune cells numbers both before and after immune challenge, suggesting a strong enhancing effect of methionine on immune cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together

  9. MRI findings of small cell neuroendocrime carcinoma of the uterine cervix: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Won, You Sun; Yi, Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Kwak, Jeong Ja [Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-10-15

    Small cell neuroendocrine carcinoma of the uterine cervix is a rare primary neoplasm, accounting for less than 5% of all uterine cervical cancers. The tumor is known to have an aggressive behavior and poor prognosis. In this article, we present the MRI findings of 5 cases of pathologically-proven small cell neuroendocrine carcinoma of the uterine cervix, including diffusion-weighted images.

  10. Splicing Regulation of Pro-Inflammatory Cytokines and Chemokines: At the Interface of the Neuroendocrine and Immune Systems.

    Science.gov (United States)

    Shakola, Felitsiya; Suri, Parul; Ruggiu, Matteo

    2015-09-07

    Alternative splicing plays a key role in posttranscriptional regulation of gene expression, allowing a single gene to encode multiple protein isoforms. As such, alternative splicing amplifies the coding capacity of the genome enormously, generates protein diversity, and alters protein function. More than 90% of human genes undergo alternative splicing, and alternative splicing is especially prevalent in the nervous and immune systems, tissues where cells need to react swiftly and adapt to changes in the environment through carefully regulated mechanisms of cell differentiation, migration, targeting, and activation. Given its prevalence and complexity, this highly regulated mode of gene expression is prone to be affected by disease. In the following review, we look at how alternative splicing of signaling molecules—cytokines and their receptors—changes in different pathological conditions, from chronic inflammation to neurologic disorders, providing means of functional interaction between the immune and neuroendocrine systems. Switches in alternative splicing patterns can be very dynamic and can produce signaling molecules with distinct or antagonistic functions and localization to different subcellular compartments. This newly discovered link expands our understanding of the biology of immune and neuroendocrine cells, and has the potential to open new windows of opportunity for treatment of neurodegenerative disorders.

  11. Luteinizing hormone-releasing hormone (LHRH) receptors in the neuroendocrine-immune network. Biochemical bases and implications for reproductive physiopathology.

    Science.gov (United States)

    Marchetti, B; Gallo, F; Farinella, Z; Romeo, C; Morale, M C

    1996-04-30

    It seems apparent that the brain-pituitary-reproductive axis and the brain-thymus-lymphoid axis are linked by an array of internal mechanisms of communication that use similar signals (neurotransmitters, peptides, growth factors, hormones) acting on similar recognition targets. Moreover, such communication networks form the basis and control of each step and every level of reproductive physiology. This work has focused on the LHRH system, a primary central and peripheral clock of both neuroendocrine and immune functions. From the initiation of a sexually organized response, the detection of sexual odors, and the induction of mating behavior, extrahypothalamic and hypothalamic LHRH orchestrates the neuroendocrine modulation of gonadotropin secretion, while its expression within the ovary directly controls specific events such as follicular atresia. The presence of LHRH receptors in oocytes clearly anticipates a potential action of the decapeptide during the process of fertilization and/or implantation. Within the thymus and other peripheral immune organs, LHRH plays a unique role of immunomodulator, contributing to the sex-dependent changes in immune responsiveness during the estrous-menstrual cycle as well as pregnancy. The reciprocity of the neuroendocrine-immune signaling systems is further supported by the ability of sex steroids to modulate thymus-dependent immune functions via direct effects on specific target genes involved in the development of sex dimorphism and sex-dimorphic immune responses, including the downregulation of immune response observed during pregnancy. Such cyclic changes in immune responsiveness could have a physiological implication, such as the decrease or suppression in cell-mediated immunity observed in the postovulatory phase of the cycle and in pregnancy, respectively, and might play a role during the implantation process and the establishment of pregnancy. In this context, the ability of corticosterone to directly inhibit both GR

  12. Nuclear medicine treatment of neuroendocrine tumours: An 8-year review

    International Nuclear Information System (INIS)

    Buscombe, J.R.; Caplin, M.E.

    2007-01-01

    The aim of this study was to review the pattern of radionuclide treatments used in a multidisciplinary neuroendocrine tumour clinic over an 8-year period 1998- 2006. The notes of all 782 patients attending the Royal Free Hospital Neuroendocrine Tumour Clinic from 1998-2006 were examined. If they had received radionuclide therapy, a note was made of the therapy given. It was found that there were six separate forms of radionuclide therapy administered. This included high activity In-111 octreotide therapy were 5-7 GBq of In-111 octreotide was given 3 monthly with between 1 and 8 times. The second form of radionuclide therapy was Y-90 lanreotide. This was given in a standard activity of 1.2GBq and given either intravenously or infused into the hepatic artery normally 3 doses were given 6-8 weeks apart and the whole procedure could be repeated if required. The third radiopeptide therapy was Y-90 octreotate. This was given in 2 activity levels 1.2GBq for intra-arterial therapies and 3GBq for intravenous therapies; these were given 8-10 weeks with a maximum of 3 cycles. When given intravenously the patient had co-administration of renal protecting amino acids. The forth form of therapy was I-131 mIBG given in two dosage regimes; a low activity regime of 3 treatments of 3Gbq 12 weeks apart and a higher activity regime of 6GBq of I-131 mIBG 12 weeks apart. These treatments could be repeated up to 3 times. The fifth treatment was intra-arterial I-131 Lipiodol for receptor negative disease and Sm-153 EDTMP for bone pain. The results of the survey are given. In total, 201 patients (26%) of patients attending a neuroendocrine tumour clinic received radionuclide therapy showing this is a major method by which these patients are treated

  13. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants.

    Directory of Open Access Journals (Sweden)

    Ana Cristina Resende Camargos

    Full Text Available Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001, adiponectin (p = 0.0007 and BDNF (p = 0.003, and serum cortisol (p = 0.048 were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS (p = 0.004, and catalase (p = 0.045 and superoxide dismutase activity (p = 0.02 were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed.

  14. Altered neuroendocrine sleep architecture in patients with type 1 diabetes.

    Science.gov (United States)

    Jauch-Chara, Kamila; Schmid, Sebastian M; Hallschmid, Manfred; Born, Jan; Schultes, Bernd

    2008-06-01

    The modulatory influence of nocturnal sleep on neuroendocrine secretory activity is increasingly recognized as a factor critical to health. Disturbances of sleep may arise from and contribute to the disease process in chronically ill patients with type 1 diabetes. Using standard polysomnography and repetitive blood sampling, neuroendocrine sleep architecture was assessed under well-controlled nonhypoglycemic conditions in 14 type 1 diabetic patients and 14 healthy control subjects matched for age, sex, and BMI. As expected, plasma glucose (P = 0.02) and serum insulin (P < 0.001) levels were constantly higher in type 1 diabetic patients than in healthy subjects throughout the night. Beside these characteristic alterations of glucose metabolism, type 1 diabetic patients displayed higher blood levels of growth hormone (P = 0.001) and epinephrine (P = 0.02) during the entire night and higher levels of ACTH (P = 0.01) as well as a tendency toward higher cortisol levels (P = 0.072) during the first night-half, compared with healthy control subjects. Patients spent slightly less time in slow wave sleep (P = 0.09) during the first night-half (where this sleep stage predominates), and overall exhibited an increased proportion of stage 2 sleep (P = 0.01). Correspondingly, assessment of mood and symptoms after sleep revealed that subjective sleep was less restorative in type 1 diabetic patients than in healthy subjects. Our data indicate distinct alterations in the neuroendocrine sleep architecture of patients with type 1 diabetes, which add to the generally adverse impact of the disease on the patients' health.

  15. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

    2014-01-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

  16. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma.

    Science.gov (United States)

    Miyasaka, Tomomitsu; Dobashi-Okuyama, Kaori; Takahashi, Tomoko; Takayanagi, Motoaki; Ohno, Isao

    2018-01-01

    Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2)-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17)-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg) cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a "neuropsychiatry phenotype" in asthma. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  17. Treatment of pancreatic neuroendocrine tumor with liver metastases

    Directory of Open Access Journals (Sweden)

    LI Zhao

    2015-05-01

    Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

  18. The endocannabinoid system and the neuroendocrine control of hydromineral balance.

    Science.gov (United States)

    Ruginsk, S G; Vechiato, F M V; Elias, L L K; Antunes-Rodrigues, J

    2014-06-01

    Endocannabinoids (ECBs) are ubiquitous lipophilic agents, and this characteristic is consistent with the wide range of homeostatic functions attributed to the ECB system. There is an increasing number of studies showing that the ECB system affects neurotransmission within the hypothalamic neurohypophyseal system. We provide an overview of the primary roles of ECBs in the modulation of neuroendocrine function and, specifically, in the control of hydromineral homeostasis. Accordingly, the general aspects of ECB-mediated signalling, as well as the specific contributions of the central component of the ECB system to the integration of behavioural and endocrine responses that control body fluid homeostasis, are discussed. © 2014 British Society for Neuroendocrinology.

  19. Dictating genomic destiny: Epigenetic regulation of pancreatic neuroendocrine tumours.

    Science.gov (United States)

    Gundara, Justin S; Jamal, Karim; Kurzawinski, Tom

    2017-04-04

    Pancreatic neuroendocrine tumours are a diverse group of neoplasms with an increasingly well-defined genomic basis. Despite this, much of what drives this disease is still unknown and epigenetic influences represent the next tier of gene, and hence disease modifiers that are of unquestionable importance. Moreover, they are of arguably more significance than the genes themselves given their malleable nature and potential to be exploited for not only diagnosis and prognosis, but also therapy. This review summarises what is known regarding the key epigenetic modifiers of disease through the domains of diagnosis, prognosis and treatment. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  20. Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome

    Directory of Open Access Journals (Sweden)

    Yen-Yu Huang

    2017-03-01

    Full Text Available The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

  1. Goblet cell carcinoid in a patient with neurofibromatosis type 1-a rare combination

    DEFF Research Database (Denmark)

    Gregersen, Tine; Holt, Nanna; Gronbaek, Henning

    2012-01-01

    Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients with neurofib......Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients...... with neurofibromatosis type 1 have an increased incidence of typical neuroendocrine tumors, but it is unknown if this is the case with goblet cell carcinoids. We describe a patient with both neurofibromatosis type 1 and goblet cell carcinoid, that according to literature would occur in 0.00017 per million per year....... This may suggest a previously unknown association between neurofibromatosis type 1 and goblet cell carcinoids....

  2. Neuroendocrine regulation of salt and water metabolism

    Directory of Open Access Journals (Sweden)

    S.M. McCann

    1997-04-01

    Full Text Available Neurons which release atrial natriuretic peptide (ANPergic neurons have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume

  3. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kam, B.L.R.; Teunissen, J.J.M.; Krenning, E.P.; Khan, S.; Vliet, E.I. van; Kwekkeboom, D.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, W.W. de [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2012-02-15

    Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with {sup 177}Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with {sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with {sup 177}Lu-DOTATATE as well as the limited side effects with additional cycles of {sup 177}Lu-DOTATATE suggest that more cycles of {sup 177}Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of {sup 90}Y-[DOTA{sup 0},Tyr{sup 3}]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with {sup 177}Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with {sup 177}Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours. (orig.)

  4. Echocardiography in functional midgut neuroendocrine tumors: When and how often.

    Science.gov (United States)

    Castillo, Javier G; Naib, Tara; Zacks, Jerome S; Adams, David H

    2017-12-01

    The management of patients with midgut neuroendocrine tumors (MNET) is rapidly evolving. Current preoperative detection rates of primary tumor sites are higher than ever and progression-free survival in patients with already advanced disease is expanding due to the implementation of novel efficacious treatment strategies. This survival benefit may potentially translate into a need for a multidisciplinary approach to an even more heterogenous variety of clinical conditions, among these, carcinoid syndrome (CS) and carcinoid heart disease (CHD). The latter often triggers substantial morbidity and mortality, hence a systematic screening, an accurate diagnosis, as well as effective interventions are critically important. The rarity of the disease has result in a relative lack of statistically powerful evidence, which in turn may have rendered significant variability between practices. In this regard, despite recent guidelines, the optimal follow-up of patients with CHD remain debatable to some authors, perhaps due to the preponderance of certain schools throughout the manuscript. Herein, we present a concise and practical guidance document on clinical screening and echocardiographic surveillance of patients with CHD based on a comprehensive review of the literature, and complemented by our experience at the Center for Carcinoid and Neuroendocrine Tumors at The Mount Sinai Hospital.

  5. Advances in the treatment of gastroenteropancreatic neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Pamela L Kunz

    2010-06-01

    Full Text Available Pamela L Kunz, George A FisherStanford University Medical Center, CA, USAAbstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs are a rare and heterogeneous class of neoplasms. While surgical resection is the mainstay of treatment, non-surgical therapies play a role in the setting of unresectable and metastatic disease. The goals of medical therapy are directed both at alleviating symptoms of peptide release and shrinking tumor mass. Biotherapies such as somatostatin analogs and interferon can decrease the secretion of peptides and inhibit their end-organ effects. A second objective for treatment of unresectable GEP-NETs is limiting tumor growth. Options for limiting tumor growth include somatostatin analogs, systemic chemotherapy, locoregional therapies, ionizing radiation, external beam radiation, and newer targeted agents. In particular, angiogenesis inhibitors, tyrosine kinase inhibitors, and mTOR inhibitors have shown early promising results. The rarity of these tumors, their resistance to standard chemotherapy, and the excellent performance status of most of these patients, make a strong argument for consideration of novel therapeutic trials.Keywords: neuroendocrine, gastroenteropancreatic, carcinoid, somatostatin

  6. Neuroendocrine Tumours : From Radiomolecular Imaging to Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    GEORGIOS eLIMOURIS

    2012-02-01

    Full Text Available Transhepatic radionuclide infusion (THRI has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan. Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabelled somatostatin analogues, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3±0.3 GBq (~ 160-180 mCi of In-111-DTPA-Phe1- Pentetreotide, 10-12 fold in total, administered monthly or of 4.1± 0.2 GBq (~105-116 mCi of Y-90 DOTA TOC, 3 fold in total or of 7.0 ± 0.4 GBq (~178-200 mCi of Lu-177 DOTA TATE, 4-6 fold in total (the choice of which being based on the tumor size, assessed by CT or MRI . Follow-up at monthly intervals has to be performed by means of ultrasonography (US. Treat- ment response has to be assessed according to the WHO criteria (RECIST or SWOG.

  7. Infection with multidrug-resistant Campylobacter coli mimicking recurrence of carcinoid syndrome: a case report of a neuroendocrine tumor patient with repeated diarrhea.

    Science.gov (United States)

    Lagler, Heimo; Kiesewetter, Barbara; Raderer, Markus

    2016-08-12

    Campylobacteriosis caused by Gram-negative bacteria of the genus Campylobacter (mainly C. jejuni and C. coli) is one of the most common gastrointestinal zoonotic infections with increased incidence in humans worldwide. The typical symptoms are severe abdominal cramps, diarrhea and sometimes fever. The clinical course of Campylobacter infection is mainly mild and after one week self-limiting, but can take several weeks in some rare cases. However, patients with neuroendocrine tumors in the gastrointestinal tract, a neoplasm of enterochromaffin/neuroendocrine cell origin, can develop severe diarrhea during progression of tumor growth caused by hormonal excess due to the tumor. Both diseases have very similar clinical symptoms and this case report elaborates the differences. So far it is known in the literature that the clinical symptoms of campylobacteriosis can mimic appendicitis or acute colitis of inflammatory bowel disease but a mimicking of recurrence of carcinoid syndrome in a patient with neuroendocrine tumor is not reported. A 72-year-old man with already diagnosed and treated metastatic neuroendocrine tumor of the terminal ileum (G1 rated, Ki-67 index 1 %) was again suffering from increasing diarrhea, abdominal cramps and weight lost. These symptoms were similar to the initial symptoms due to the tumor which improved at the time after total resection of the primary in the terminal ileum and regular therapy with long-acting release depot octreotide intramuscularly. As progression/tachyphylaxis in symptomatic patients with carcinoid syndrome undergoing therapy, reassessment of disease and analysis of tumor markers was initiated, and the interval of intramuscular injections was shortened. Radiological findings and tumor marker levels disclosed no evidence of neuroendocrine tumor progression and the symptoms continued. After 4 weeks with symptoms the patient developed additionally fever. Due to impaired renal function and elevated signs of systemic

  8. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Directory of Open Access Journals (Sweden)

    Severi S

    2017-01-01

    Full Text Available Stefano Severi,1 Ilaria Grassi,1 Silvia Nicolini,1 Maddalena Sansovini,1 Alberto Bongiovanni,2 Giovanni Paganelli1 1Nuclear Medicine Unit, 2Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS, Meldola, Italy Abstract: Peptide receptor radionuclide therapy (PRRT, developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate. These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide and peptide receptor affinity (due to the analog but share the common characteristic of binding specific membrane somatostatin receptors that are (generally overexpressed in neuroendocrine neoplasms (NENs and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs] and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs. They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases. Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon. Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors

  9. The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

    Directory of Open Access Journals (Sweden)

    Giuseppe Lamberti

    2018-03-01

    Full Text Available The mechanistic target of rapamycin (mTOR is part of the phosphoinositide-3-kinase (PI3K/protein kinase B (AkT/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs, in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs.

  10. Update on neuroendocrine regulation and medical intervention of reproduction in birds.

    Science.gov (United States)

    Mans, Christoph; Taylor, W Michael

    2008-01-01

    In avian species, reproductive disorders and undesirable behaviors commonly reflect abnormalities in the neuroendocrine regulation of the reproductive system. Current treatment options are often disappointing, show no long-lasting effect, or have significant side effects. A possible reason for our lack of success is a dearth of knowledge of the underlying neuroendocrine, behavioral, and autonomous physiology of the reproductive processes. Tremendous progress has been made in the last few years in our understanding of the neuroendocrine control of reproduction in birds. Advantage should be taken of these experimentally derived data to develop appropriate and safe treatment protocols for avian patients suffering from reproductive disorders.

  11. Endocrine and neuroendocrine regulation of fathering behavior in birds.

    Science.gov (United States)

    Lynn, Sharon E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Although paternal care is generally rare among vertebrates, care of eggs and young by male birds is extremely common and may take on a variety of forms across species. Thus, birds provide ample opportunities for investigating both the evolution of and the proximate mechanisms underpinning diverse aspects of fathering behavior. However, significant gaps remain in our understanding of the endocrine and neuroendocrine influences on paternal care in this vertebrate group. In this review, I focus on proximate mechanisms of paternal care in birds. I place an emphasis on specific hormones that vary predictably and/or unpredictably during the parental phase in both captive and wild birds: prolactin and progesterone are generally assumed to enhance paternal care, whereas testosterone and corticosterone are commonly-though not always correctly-assumed to inhibit paternal care. In addition, because endocrine secretions are not the sole mechanistic influence on paternal behavior, I also explore potential roles for certain neuropeptide systems (specifically the oxytocin-vasopressin nonapeptides and gonadotropin inhibitory hormone) and social and experiential factors in influencing paternal behavior in birds. Ultimately, mechanistic control of fathering behavior in birds is complex, and I suggest specific avenues for future research with the goal of narrowing gaps in our understanding of this complexity. Such avenues include (1) experimental studies that carefully consider not only endocrine and neuroendocrine mechanisms of paternal behavior, but also the ecology, phylogenetic history, and social context of focal species; (2) investigations that focus on individual variation in both hormonal and behavioral responses during the parental phase; (3) studies that investigate mechanisms of maternal and paternal care independently, rather than assuming that the mechanistic foundations of care are similar between the sexes; (4

  12. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

  13. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    International Nuclear Information System (INIS)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J.

    2003-01-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  14. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    Energy Technology Data Exchange (ETDEWEB)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J

    2003-07-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  15. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Management of follow-up of neuroendocrine neoplasias.

    Science.gov (United States)

    Pape, Ulrich-Frank; Maasberg, Sebastian; Jann, Henning; Pschowski, René; Krüger, Sandrine; Prasad, Vikas; Denecke, Timm; Wiedenmann, Bertram; Pascher, Andreas

    2016-01-01

    Neuroendocrine neoplasias (NEN) comprise heterogeneous epithelial neoplasms with a large variety of clinical presentations, treatment options and outcomes. Since potentially all NEN bear malignant potential it is important for long-term clinical management and improvement of outcome to decide on successful and oncologically and economically meaningful follow-up strategies. Evidence-based outcome data validating specific follow-up strategies are, however, not available to date and thus outcome data, known prognostic factors and clinical experience guide the decisions on follow-up regimens. The review summarizes general recommendations as well as specific considerations based on tumor entities, clinicopathological tumor characteristics and clinical experience. Follow-up shall serve the patient to improve outcome, benefit from more effective therapies and suffer less from unnecessary and/or toxic therapeutic interventions and finally preserve or gain a good quality of life. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Metastatic primary neuroendocrine carcinoma of the breast (NECB

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Tsai

    2018-03-01

    Full Text Available Neuroendocrine carcinoma of the breast (NECB is a subtype of breast cancer. The diagnostic criteria of primary NECB were established in 2003 and updated in 2012. It is a rare entity, and few studies have reported the histogenesis, immunohistochemistry for a pathological diagnosis, clinical behavior, therapeutic strategies, and the prognostic factors. Because of the rarity of this disease, consistent diagnostic criteria will remind physicians of this disease when making a differential diagnosis to enable a timely diagnosis and prompt treatment. Herein, we report a case of primary NECB who presented with a history of right hip pain arising from an osteolytic lesion in the right acetabulum and ischium. The course of investigation started with metastasis in the right hip and concluded with a diagnosis of NECB. In addition to the case report, we also conducted a literature review.

  18. Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

    Science.gov (United States)

    Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

    2014-02-01

    The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

  19. High expression of dopamine receptor subtype 2 in a large series of neuroendocrine tumors.

    Science.gov (United States)

    Grossrubatscher, Erika; Veronese, Silvio; Ciaramella, Paolo Dalino; Pugliese, Raffaele; Boniardi, Marco; De Carlis, Luciano; Torre, Massimo; Ravini, Mario; Gambacorta, Marcello; Loli, Paola

    2008-12-01

    To evaluate by immumohistochemistry the presence of DR subtype 2 (D2R) in well differentiated NETs of different sites and in normal islet cells. Recent data in vitro and in vivo support that dopaminergic drugs might exert an inhibitory effect on hormone secretion and, possibly, on tumor growth in neuroendocrine tumors (NET)s. Their potential therapeutic role needs the demonstration of dopamine receptors (DR) in tumor cells. Little is known on the expression of DR in NETs. 85% of samples (100% of bronchial carcinoids and 93% of islet cell tumors) showed positivity for D2R; intensity of immunoreaction in NETs was similar or higher than in pituitary (54% and respectively 31% of cases). D2R positivity in more than 70% of tumor cells was observed in 46% of samples. Same intensity of D2R-immunoreactivity was found in pituitary and normal islet cells. No differences in D2R expression were recorded on considering tumor grading, size, proliferative activity, presence of metastases, endocrine activity and gender. A significant difference (62.5% vs 96.4%, p = 0.039) was observed in the prevalence of D2R expression between patients with more aggressive tumors and patients without recurrence/progression of disease during follow-up. 46 NET samples from 44 patients and normal endocrine pancreatic tissue were studied. D2R-staining was performed on NETs and compared with six non-secreting pituitary adenomas and related to clinical-pathological data. The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs.

  20. D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems.

    Science.gov (United States)

    Ota, Nobutoshi; Shi, Ting; Sweedler, Jonathan V

    2012-11-01

    D-Aspartate (D-Asp) is an endogenous amino acid in the central nervous and reproductive systems of vertebrates and invertebrates. High concentrations of D-Asp are found in distinct anatomical locations, suggesting that it has specific physiological roles in animals. Many of the characteristics of D-Asp have been documented, including its tissue and cellular distribution, formation and degradation, as well as the responses elicited by D-Asp application. D-Asp performs important roles related to nervous system development and hormone regulation; in addition, it appears to act as a cell-to-cell signaling molecule. Recent studies have shown that D-Asp fulfills many, if not all, of the definitions of a classical neurotransmitter-that the molecule's biosynthesis, degradation, uptake, and release take place within the presynaptic neuron, and that it triggers a response in the postsynaptic neuron after its release. Accumulating evidence suggests that these criteria are met by a heterogeneous distribution of enzymes for D-Asp's biosynthesis and degradation, an appropriate uptake mechanism, localization within synaptic vesicles, and a postsynaptic response via an ionotropic receptor. Although D-Asp receptors remain to be characterized, the postsynaptic response of D-Asp has been studied and several L-glutamate receptors are known to respond to D-Asp. In this review, we discuss the current status of research on D-Asp in neuronal and neuroendocrine systems, and highlight results that support D-Asp's role as a signaling molecule.

  1. A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1

    Directory of Open Access Journals (Sweden)

    Nishi Takeshi

    2012-07-01

    Full Text Available Abstract Patients with neurofibromatosis-1 (NF-1 sometime develop neuroendocrine tumors (NET. Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET. A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast-enhanced computed tomography scan demonstrated a 30-mm tumor in the head of the pancreas. The scan showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with an acinus-like structure. The tumor was diagnosed as NET G2 according to the WHO classification (2010. The product of theNF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.

  2. INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors.

    Science.gov (United States)

    Rooper, Lisa M; Bishop, Justin A; Westra, William H

    2018-05-01

    The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck. We performed INSM1 immunohistochemistry on NE tumors (n=97) and non-NE tumors (n=626) across all histologic grades and anatomic subsites of the head and neck. INSM1 was positive in all types of head and neck NE tumors evaluated here (99.0% sensitivity), including middle ear adenoma, pituitary adenoma, paraganglioma, medullary thyroid carcinoma, olfactory neuroblastoma, small cell carcinoma, large cell NE carcinoma, and sinonasal teratocarcinosarcoma. Notably, it was positive in the vast majority of high-grade NE malignancies (95.8% sensitivity). INSM1 also was negative in almost all non-NE tumors (97.6% specificity) with the highest rates of reactivity in alveolar rhabdomyosarcoma and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1 (SMARCB1)-deficient sinonasal carcinoma. These findings confirm that INSM1 may be used as a standalone first-line marker of NE differentiation for tumors of the head and neck.

  3. First-line chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Bongiovanni A

    2015-12-01

    Full Text Available Alberto Bongiovanni,1 Nada Riva,1 Marianna Ricci,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Flavia Foca,2 Laura Mercatali,1 Stefano Severi,3 Dino Amadori,4 Toni Ibrahim1 1Osteoncology and Rare Tumors Center, 2Unit of Biostatistics and Clinical Trials, 3Nuclear Medicine Unit, 4Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS, Meldola, FC, Italy Background and aim: To investigate the efficacy of platinum-based chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (mGEP-NEC and define predictive and prognostic factors. Methods: Twenty mGEP-NEC patients were treated with cisplatin or carboplatin/etoposide between April 2010 and October 2014. Both large-cell and small-cell histologies were included. Cisplatin 25 mg/m2 was administered on days 1–3 followed by etoposide 100 mg/m2 on days 1–3 every 21 days. Carboplatin 300 mg/m2 was administered on day 1 followed by etoposide 100 mg/m2 on days 1–3. Results: Of the 19 evaluable patients, 13 obtained a partial response, four showed stable disease, and two progressed. Median overall survival (mOS was 13.5 months and median progression-free survival (mPFS was 10.9 months. Gallium-68 positron emission tomography/computerizsed tomography-positive patients had a higher, albeit not significantly, OS than those with negative results (75% vs 34.3% at 18 months; P=0.06. mPFS was 19.3 and 6.3 months (P<0.01 in mGEP-NEC patients with Ki67 ≤55% or >55%, respectively. mOS was 8.1 months in the latter group but was not reached in the Ki67 ≤55% group (P-value =0.039. Patients with a lower body mass index (BMI had a better prognosis in terms of both OS and PFS. Patients with BMI ≥25 had a mOS of 11.7 months (P=0.0293 and a mPFS of 6.2 months (P=0.0057. Conclusion: Platinum-based chemotherapy showed good efficacy in mGEP-NEC patients. Those with Ki67 ≤55%, positive Gallium-68 positron emission

  4. The suprachiasmatic nucleus-paraventricular nucleus interactions: a bridge to the neuroendocrine and autonomic nervous system

    NARCIS (Netherlands)

    Buijs, R. M.; Hermes, M. H.; Kalsbeek, A.

    1998-01-01

    Vasopressin (VP) is one of the principal neurotransmitters of the suprachiasmatic nucleus (SCN). By means of anatomical, physiological and electrophysiological techniques we have demonstrated that VP containing pathways from the SCN serve to affect neuroendocrine and 'autonomic' neurons in the

  5. Recent advances in the understanding of sepsis-induced alterations in the neuroendocrine system.

    Science.gov (United States)

    Wahab, Fazal; Atika, Bibi; Oliveira-Pelegrin, Gabriela Ravanelli; Rocha, Maria José Alves

    2013-12-01

    Sepsis is a fatal systemic inflammatory disease. It is caused by an immune system inflammatory response to the entry of microorganisms or their products into the blood circulatory system. The pathophysiological mechanisms of sepsis are still poorly understood. The presence of microorganisms in the systemic circulation causes activation of the immune system, which in turn leads to a robust release of inflammatory cytokines. These inflammatory cytokines result in alterations across all important physiological systems, including the neuroendocrine system. Neuroendocrine responses differ between the acute and the late phase of sepsis. In the acute phase there are robust alterations in the secretion of neuroendocrine hormones in response to body demand. In the late phase, the plasma concentrations of some hormones remain low, despite heavy systemic demand, whereas several others increase despite of diminished needs. In this review, we give a brief overview on sepsis-induced major alterations in neuroendocrine secretions, and summarize current knowledge about mechanisms and targets for their treatment.

  6. Basal and exercise-induced neuroendocrine activation in patients with heart failure and in normal subjects

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Appel, Jon; Hildebrandt, Per

    2004-01-01

    BACKGROUND: Neuroendocrine activation is a pathophysiological response and an important prognostic marker in patients with chronic heart failure (CHF). Although chronic activation is well described, data on the responsiveness of the hormone systems are more limited. Most previous studies have...

  7. Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Galleberg, R. B.; Knigge, U; Tiensuu Janson, E.

    2017-01-01

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce....

  8. Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response

    Science.gov (United States)

    New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the re...

  9. Ampullary neuroendocrine tumor presenting with biliary obstruction and gastric outlet obstruction

    Directory of Open Access Journals (Sweden)

    Praveer Rai

    2012-01-01

    Full Text Available Neuroendocrine tumors of the ampulla of Vater are extremely rare cause of extrahepatic biliary obstruction and further rarer cause of duodenal obstruction, and only a few cases have been reported in the literature. Herein we report a case of ampullary neuroendocrine tumor in a 75-year-old woman who presented with biliary obstruction and gastric outlet obstruction palliated with metal biliary and duodenal stenting with relief of jaundice and vomiting at 1 month of follow-up.

  10. MashI Expression Is Induced in Neuroendocrine Prostate Cancer Upon the Loss of Foxa2

    OpenAIRE

    Gupta, Aparna; Yu, Xiuping; Case, Tom; Paul, Manik; Shen, Michael M.; Kaestner, Klaus H.; Matusik, Robert J.

    2012-01-01

    Neuroendocrine (NE) prostate tumors and neuroendocrine differentiation (NED) in prostatic adenocarcinomas have been associated with poor prognosis. In this study, we used the TRAMP mouse model that develops NE prostate tumors to identify key factors that can lead to NED. We have previously reported that NE tumors express the forkhead transcription factor, Foxa2, Mash1 (mouse achaete scute homolog-1), as well as Synaptophysin. In TRAMP, the prostatic intraepithelial neoplasia (PIN) first expre...

  11. Carcinome neuroendocrine du sein: à propos d'un cas et revue de ...

    African Journals Online (AJOL)

    Le carcinome neuroendocrine primitif du sein est une tumeur rare qui a été reconnue par la dernière édition de la classification OMS du cancer du sein publiée en 2003. Le diagnostic est évoqué sur des critères morphologiques et confirmé par l'expression des marqueurs neuroendocrines (chromogranine et ...

  12. The Structure of the Neuroendocrine Hypothalamus: The Neuroanatomical Legacy of Geoffrey Harris

    Science.gov (United States)

    Watts, Alan G.

    2015-01-01

    In November 1955 Geoffrey Harris published a paper based on the Christian A. Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing this Harris introduced a set of properties that would help define the neuroendocrine hypothalamus. They included: a) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; b) an analogy between the representation of body parts in sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and c) the idea that neuroendocrine neurons were motor neurons, with the pituitary stalk functioning as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons had to pass to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries being made in the early 1950s were beginning to influence neuroendocrinology? The present article discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and within this framework, how novel and powerful techniques are taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. PMID:25994006

  13. Comparison of WHO 2000 and WHO 2010 classifications of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Karakuş, Esra; Helvacı, Ayşe; Ekinci, Ozgür; Dursun, Ayşe

    2014-02-01

    Grading and staging are important in gastroenteropancreatic neuroendocrine tumors for directing treatment. In this study, we evaluated the histopathological parameters of gastroenteropancreatic neuroendocrine tumors and statistically analyzed the correlations of these parameters between the World Health Organization (WHO) 2000 and 2010 classifications. A total of 77 cases diagnosed as neuroendocrine tumors were included in the study. Cases were classified according to the WHO 2000 and WHO 2010 classification systems, and the differences and correlations between the two systems were discussed. Among the 50 cases that were diagnosed as well-differentiated neuroendocrine tumor according to WHO 2000, 45 were found to be Grade 1 and 5 were found to be Grade 2 according to the WHO 2010 classification. Among the 8 cases with well-differentiated neuroendocrine carcinoma according to WHO 2000; 5 and 3 were Grade 1 and Grade 2, respectively, according to the WHO 2010 classification. All of the 19 cases with poorly differentiated neuroendocrine carcinoma according to WHO 2000 were found to be Grade 3 according to the WHO 2010 classification. No differences were found between the classifications in the poorly differentiated group with a full correlation between the two classifications. Although WHO 2000 seems to be a better classification to predict prognosis, since it is based on various parameters, such as depth of invasion, angiolymphatic invasion, and presence of metastasis, it was concluded that there was no difference between the WHO 2000 and WHO 2010 classification, which is based on only the number of mitoses and Ki-67 proliferation index.

  14. 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris.

    Science.gov (United States)

    Watts, Alan G

    2015-08-01

    In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. © 2015 Society for Endocrinology.

  15. A fluorescence-coupled assay for gamma aminobutyric acid (GABA reveals metabolic stress-induced modulation of GABA content in neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Joseph E Ippolito

    Full Text Available Pathways involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA have been implicated in the pathogenesis of high grade neuroendocrine (NE neoplasms as well as neoplasms from a non-NE lineage. Using The Cancer Genome Atlas, overexpression of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1, was found to be associated with decreased disease free-survival in prostate adenocarcinoma and decreased overall survival in clear cell renal cell carcinomas. Furthermore, GAD1 was found to be expressed in castrate-resistant prostate cancer cell lines, but not androgen-responsive cell lines. Using a novel fluorescence-coupled enzymatic microplate assay for GABA mediated through reduction of resazurin in a prostate neuroendocrine carcinoma (PNEC cell line, acid microenvironment-induced stress increased GABA levels while alkaline microenvironment-induced stress decreased GABA through modulation of GAD1 and glutamine synthetase (GLUL activities. Moreover, glutamine but not glucose deprivation decreased GABA through modulation of GLUL. Consistent with evidence in prokaryotic and eukaryotic organisms that GABA synthesis mediated through GAD1 may play a crucial role in surviving stress, GABA may be an important mediator of stress survival in neoplasms. These findings identify GABA synthesis and metabolism as a potentially important pathway for regulating cancer cell stress response as well as a potential target for therapeutic strategies.

  16. Bronchial neuroendocrine elements in late post-radiation stage in humans after total body irradiation

    International Nuclear Information System (INIS)

    Pilmane, M.; Luts, A.; Sundler, F.; Kjoerell, U.; Forsgren, S.

    1998-01-01

    It is not known how long-term total body irradiation affects the neuroendocrine cells (Nc) and peptidergic innervation in the bronchial wall. This study examined, by immunohistochemical and radioimmunoassay (RIA) techniques, the distribution of NC and neuropeptide-containing nerve fibres in the large bronchi of Chernobyl nuclear accident cleanup workers displaying pulmonary fibrosis and metaplastic epithelium. Bronchial mucous and submucous layers from 16 Chernobyl patients and 6 control subjects were examined by conventional light microscopy and immunohistochemical techniques for determination of protein gene product 9.5 (PGP), chromogranin A, chromogranin A and B (CAB), calcitonin gene-related peptide (CGRP), calcitonin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), helospectin I, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), serotonin (5-hydroxyltryptamine, 5-HT), and substance P (SP). Additionally, bronchial biopsies from 6 Chernobyl cleanup workers and 3 control patients were examined by RIA for VIP and NPY/peptideYY-Ievels. The Chernobyl patients were examined 10 years after exposure during the cleanup works in the Chernobyl Atomic Electric Power Station. PGP immunoreactive nerve fibres appeared to be more frequent in the bronchial wall after long term irradiation as compared with controls. However, no specific alterations in the amounts of NPY-, PACAP-, helospectin-, SP- and CGRP-immunoreactive nerve fibres were seen in bronchi of control and Chernobyl patients. 5-HT -immunoreactive NC appeared to be more numerous in normal bronchial epithelium adjacent to metaplastic epithelium, in which numerous CAB- immunoreactive NC were seen in Chernobyl patients. RIA for VIP and NPY/PYY showed individual variations in the levels of these peptides in the bronchial tissue. In two cases (one Chernobyl patient and one control patient) there was a high concentration of VIP in parallel with a high concentration of NPY

  17. Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Herrera-Martínez, Aura D; Gahete, Manuel D; Pedraza-Arevalo, Sergio; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Serrano-Blanch, Raquel; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

    2018-02-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1-sst5) in GEP-NETs. The expression of SST system components in GEP-NETs was determined, compared with that of non-tumor adjacent and normal tissues and correlated with clinical and histological characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples were included. Cell viability in NET cell lines was determined in response to specific SSAs. Normal samples and non-tumor adjacent tissues presented a similar expression profile, with appreciable expression of sst2 and sst3, and a lower expression of the other receptors. In contrast, cortistatin, sst1, sst4, and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed in less differentiated tumors. Some SST system components were related to vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced viability in BON-1 cells, while they, similar to octreotide and pasireotide, increased viability in QGP-1 cells. These results provide novel information on SST system pathophysiology in GEP-NETs, including relevant associations with clinical-histological parameters, which might help to better understand the intrinsic heterogeneity of NETs and to identify novel biomarkers and/or targets with potential prognostic and/or therapeutic value for GEP-NETs patients.

  18. Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

    Science.gov (United States)

    Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

    2001-01-01

    Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

  19. Neuronal, neurohormonal, and autocrine control of Xenopus melanotrope cell activity

    NARCIS (Netherlands)

    Roubos, E.W.; Scheenen, W.J.J.M.; Jenks, B.G.

    2005-01-01

    Amphibian pituitary melanotropes are used to investigate principles of neuroendocrine translation of neural input into hormonal output. Here, the steps in this translation process are outlined for the melanotrope cell of Xenopus laevis, with attention to external stimuli, neurochemical messengers,

  20. Pathogenesis and treatment of HIV infection: the cellular, the immune system and the neuroendocrine systems perspective.

    Science.gov (United States)

    Chereshnev, V A; Bocharov, G; Bazhan, S; Bachmetyev, B; Gainova, I; Likhoshvai, V; Argilaguet, J M; Martinez, J P; Rump, J A; Mothe, B; Brander, C; Meyerhans, A

    2013-06-01

    Infections with HIV represent a great challenge for the development of strategies for an effective cure. The spectrum of diseases associated with HIV ranges from opportunistic infections and cancers to systemic physiological disorders like encephalopathy and neurocognitive impairment. A major progress in controlling HIV infection has been achieved by highly active antiretroviral therapy (HAART). However, HAART does neither eliminate the virus reservoirs in form of latently infected cells nor does it completely reconstitute immune reactivity and physiological status. Furthermore, the failure of the STEP vaccine trial and the only marginal efficacies of the RV144 trial together suggest that the causal relationships between the complex sets of viral and immunological processes that contribute to protection or disease pathogenesis are still poorly understood. Here, we provide an up-to-date overview of HIV-host interactions at the cellular, the immune system and the neuroendocrine systems level. Only by integrating this multi-level knowledge one will be able to handle the systems complexity and develop new methodologies of analysis and prediction for a functional restoration of the immune system and the health of the infected host.

  1. Neuroendocrine system of the digestive tract in Rhamdia quelen juvenile: an immunohistochemical study.

    Science.gov (United States)

    Hernández, D R; Vigliano, F A; Sánchez, S; Bermúdez, R; Domitrovic, H A; Quiroga, M I

    2012-08-01

    In this work, an immunohistochemical study was performed to determine the distribution and relative frequencies of some neuromodulators of the digestive tract of silver catfish (Rhamdia quelen). The digestive tract of silver catfish was divided into six portions; the oesophagus, stomach, intestine (ascendant, descendant and convoluted segments), and rectum. Immunohistochemical method using a pool of specific antisera against-gastrin, -cholecystokinin-8, -leu-enkephalin, -neuropeptide Y, -calcitonin gene-related peptide (CGRP), and -vasoactive intestinal peptide (VIP) was employed. Immunoreactivity to all antisera was identified in neuroendocrine cells (NECs) localized in the gut epithelium, although no reaction was observed in the oesophagus or stomach. The morphology of NECs immunopositive to each antibody was similar. They were slender in shape, with basally located nucleus, and their main axis perpendicular to the basement membrane. The number of NECs immunoreactive to all antisera was higher in the ascendant and descendant intestine, exhibiting a decreasing trend toward distal segments of the gut. In addition, immunoreactivity to CGRP and VIP was observed in the myenteric plexus and nerve fibers distributed in the mucosal, submucosal and muscular layers. The higher number of immunopositive NECs in the ascendant and descendant intestine may indicate the primary role of these segments in the control of food intake by means of orexigenic and anorexigenic peripheral signals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Retrospective review of 21 cases of neuroendocrine tumors and review of literature

    International Nuclear Information System (INIS)

    Ferrari, A.; Alonso, S.; Cordoba, A.; Vazquez, A.

    2010-01-01

    Objective: literature review and case histories. Neuroendocrine tumors (Nets) are considered rare and comprise a group very heterogeneous with different prognosis and evolution. They represent less than 1% of all malignant tumors and most originate from the gastrointestinal tract in enterocromoafines cells are widely distributed in the same: in the stomach, duodenum, pancreas, small, colon and rectum. Carcinoid tumors Gastrointestinal represent over 70% of all tumors (Nets) in humans. And frequently they are finding their debut as disseminated disease, coinciding our review. 21 records were retrospectively analyzed between 1995 and June 2010. No significant difference in gender, of these 9 patients were 12 female and male sex. Ages ranged from 36 years to 83 years, with an average of 63 years. The locations were distributed as follows: 6 patients with small bowel tumor, 2 with blind tumor, 2 esophageal tumor , 1 patient with pancreatic tumor, 1 patient with stomach tumor, 2 patients with retroperitoneal disease in which failed to define the primary, 2 patients with tumor in breast, 3 patients with lung tumor, 1 patient with piriform sinus tumor and 1 patient with parotid tumor. Of the 21 patients, only 4 sometime had functional syndrome characterized by diarrhea and flushing. The treatments that received these patients were also very heterogeneous. From these patients, only one died in 2008 and the others are still alive, some in control and other treatment. Because of the number of patients seen and the therapeutic variability the statistical analysis no was done

  3. Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

    Directory of Open Access Journals (Sweden)

    Tiago Nunes da Silva

    2018-04-01

    Full Text Available Non-functional pancreatic neuroendocrine tumours (NETs can present with advanced local or distant (metastatic disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

  4. MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Xiaohui; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Zhang, Fang; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); Ban, Xiaohua [Sun Yat-Sen University, Medical Imaging and Minimally Invasive Interventional Center and State Key Laboratory of Oncology in Southern China, Cancer Center, Guangzhou, Guangdong (China); Wang, Charles Qian [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); University of New South Wales, JMO, Westmead Hospital, Sydney (Australia)

    2016-12-15

    To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 x 10{sup -3} mm{sup 2}/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. (orig.)

  5. Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemo-resistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

    Science.gov (United States)

    Cui, Yun; Sun, Yin; Hu, Shuai; Luo, Jie; Li, Lei; Li, Xin; Yeh, Shuyuan; Jin, Jie; Chang, Chawnshang

    2016-01-01

    Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa. PMID:27375022

  6. CLINICAL VALUE OF CHROMOGRANIN A IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

    Directory of Open Access Journals (Sweden)

    N. V. Lyubimova

    2015-01-01

    Full Text Available Background: Neuroendocrine tumors (NET is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA.Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark.Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001. In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l. The highest CgA medians were detected in patients with small intestinal (183.9 U/l, colon (148.4 U/l and pancreatic (135.9 U/l NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l and those with carcinoid syndrome (352 U/l. The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8% with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

  7. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects

    DEFF Research Database (Denmark)

    Zhu, Xiaorong; Zhou, An; Dey, Arunangsu

    2002-01-01

    The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway. They are expressed together or separately in neuroendocrine cells throughout the brain and dispersed endocrine system in both...... proopiomelanocortin to adrenocorticotropic hormone, islet proinsulin to insulin and intestinal proglucagon to glucagon-like peptide-1 and -2. Mice lacking PC1/3 are normal at birth, but fail to grow normally and are about 60% of normal size at 10 weeks. They lack mature GHRH, have low pituitary growth hormone (GH......) and hepatic insulin-like growth factor-1 mRNA levels and resemble phenotypically the "little" mouse (Gaylinn, B. D., Dealmeida, V. I., Lyons, C. E., Jr., Wu, K. C., Mayo, K. E. & Thorner, M. O. (1999) Endocrinology 140, 5066-5074) that has a mutant GHRH receptor. Despite a severe defect in pituitary...

  8. Diffuse neuroendocrine system and mitochondrial diseases: molecular and cellular bases of pathogenesis, new approaches to diagnosis and therapy.

    Science.gov (United States)

    Kvetnoy, Igor M.; Hernández-Yago, José; Hernández, José Miguel; Kvetnaia, Tatiana V.; Reiter, Russel J.; Khavinson, Vladimir Kh.

    2000-01-01

    Structural and functional alterations of mitochondria have been shown to be responsible for a wide variety of clinical disorders that are referred to as "mitochondrial diseases." It is now obvious that many factors are involved in transport of mitochondrial proteins including cytokines, chaperones, chemokines, neurosteroids, ubiquitin and many others. At the same time the participation and the role of biogenic amines and peptide hormones (which are produced by the diffuse neuroendocrine system cells located in different organs) in endogenous mechanisms of mitochondrial diseases are still unknown. Taking into account the wide spectrum of biological effects of biogenic amines and peptide hormones, and especially their regulatory role for intercellular communication, it seems important to analyze the possible participation of these molecules in the pathogenesis of mitochondrial disorders as well as to draw up new ways for elaboration of new markers for lifetime diagnosis, definition of prognosis and efficiency of specific therapy in neurodegenerative diseases.

  9. Members of the crustacean hyperglycemic hormone (CHH) peptide family are differentially distributed both between and within the neuroendocrine organs of Cancer crabs: implications for differential release and pleiotropic function.

    Science.gov (United States)

    Hsu, Yun-Wei A; Messinger, Daniel I; Chung, J Sook; Webster, Simon G; de la Iglesia, Horacio O; Christie, Andrew E

    2006-08-01

    The crustacean hyperglycemic hormone (CHH) family of peptides includes CHH, moult-inhibiting hormone (MIH) and mandibular organ-inhibiting hormone (MOIH). In the crab Cancer pagurus, isoforms of these peptides, as well as CHH precursor-related peptide (CPRP), have been identified in the X-organ-sinus gland (XO-SG) system. Using peptides isolated from the C. pagurus SG, antibodies to each family member and CPRP were generated. These sera were then used to map the distributions and co-localization patterns of these peptides in the neuroendocrine organs of seven Cancer species: Cancer antennarius, Cancer anthonyi, Cancer borealis, Cancer gracilis, Cancer irroratus, Cancer magister and Cancer productus. In addition to the XO-SG, the pericardial organ (PO) and two other neuroendocrine sites contained within the stomatogastric nervous system, the anterior cardiac plexus (ACP) and the anterior commissural organ (ACO), were studied. In all species, the peptides were found to be differentially distributed between the neuroendocrine sites in conserved patterns: i.e. CHH, CPRP, MIH and MOIH in the XO-SG, CHH, CPRP and MOIH in the PO, and MOIH in the ACP (no immunolabeling was found in the ACO). Moreover, in C. productus (and probably in all species), the peptides present in the XO-SG and PO were differentially distributed between the neurons within each of these neuroendocrine organs (e.g. CHH and CPRP in one set of XO somata with MIH and MOIH co-localized in a different set of cell bodies). Taken collectively, the differential distributions of CHH family members and CPRP both between and within the neuroendocrine organs of crabs of the genus Cancer suggests that each of these peptides may be released into the circulatory system in response to varied, tissue-specific cues and that the PO- and/or ACP-derived isoforms may possess functions distinct from those classically ascribed to their release from the SG.

  10. Identifying tumor in pancreatic neuroendocrine neoplasms from Ki67 images using transfer learning.

    Science.gov (United States)

    Niazi, Muhammad Khalid Khan; Tavolara, Thomas Erol; Arole, Vidya; Hartman, Douglas J; Pantanowitz, Liron; Gurcan, Metin N

    2018-01-01

    The World Health Organization (WHO) has clear guidelines regarding the use of Ki67 index in defining the proliferative rate and assigning grade for pancreatic neuroendocrine tumor (NET). WHO mandates the quantification of Ki67 index by counting at least 500 positive tumor cells in a hotspot. Unfortunately, Ki67 antibody may stain both tumor and non-tumor cells as positive depending on the phase of the cell cycle. Likewise, the counter stain labels both tumor and non-tumor as negative. This non-specific nature of Ki67 stain and counter stain therefore hinders the exact quantification of Ki67 index. To address this problem, we present a deep learning method to automatically differentiate between NET and non-tumor regions based on images of Ki67 stained biopsies. Transfer learning was employed to recognize and apply relevant knowledge from previous learning experiences to differentiate between tumor and non-tumor regions. Transfer learning exploits a rich set of features previously used to successfully categorize non-pathology data into 1,000 classes. The method was trained and validated on a set of whole-slide images including 33 NETs subject to Ki67 immunohistochemical staining using a leave-one-out cross-validation. When applied to 30 high power fields (HPF) and assessed against a gold standard (evaluation by two expert pathologists), the method resulted in a high sensitivity of 97.8% and specificity of 88.8%. The deep learning method developed has the potential to reduce pathologists' workload by directly identifying tumor boundaries on images of Ki67 stained slides. Moreover, it has the potential to replace sophisticated and expensive imaging methods which are recently developed for identification of tumor boundaries in images of Ki67-stained NETs.

  11. [Genetic and neuroendocrine aspects in autism spectrum disorder].

    Science.gov (United States)

    Oviedo, Norma; Manuel-Apolinar, Leticia; de la Chesnaye, Elsa; Guerra-Araiza, Christian

    The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  12. Abnormal neuroendocrine response to clomipramine in hereditary affective psychosis.

    Science.gov (United States)

    Cordes, Joachim; Larisch, Rolf; Henning, Uwe; Thünker, Johanna; Werner, Christian; Orozco, Guillermo; Mayoral, Fermín; Rivas, Fabio; Auburger, Georg; Tosch, Marco; Rietschel, Marcella; Gaebel, Wolfgang; Müller, Hans-Wilhelm; Klimke, Ansgar

    2009-01-01

    Blunting of prolactin response after serotonergic stimulation during a major depressive episode has been described by several investigators. In this study, the neuroendocrine responses to clomipramine were assessed in remitted patients suffering from hereditary depression. Twenty remitted patients from 11 large families with multigenerational, multiple cases of major affective disorder (bipolar disorder n=15, recurrent depression n=5, according DSM-IV) and 12 healthy relatives were investigated. After intravenous application of 12.5 mg of the serotonin re-uptake inhibitor clomipramine, serum prolactin and cortisol levels were analysed. Patients and comparison group did not differ significantly with respect to age, baseline prolactin and cortisol concentrations. A gender effect was found in an exploratory analysis for prolactin but not for cortisol and therefore the data for prolactin were analysed separately. After clomipramine infusion, the increase of cortisol was significantly lower in patients than in the comparison group (P=.046). For prolactin, this effect could be found in the male (P=.012) as well as in the female (P=.007) subsample. These results suggest that blunted prolactin and cortisol responses to serotonergic stimulation are characteristic for remitted depressive patients with previous episodes of major affective disorders. (c) 2009 Wiley-Liss, Inc.

  13. Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

    Science.gov (United States)

    Gore, Andrea C.

    2009-01-01

    The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

  14. Metabonomic profiling: a novel approach in neuroendocrine neoplasias.

    Science.gov (United States)

    Kinross, James M; Drymousis, Panagiotis; Jiménez, Beatriz; Frilling, Andrea

    2013-12-01

    A metabonomic phenotyping strategy was developed as part of a pilot study to define a diagnostic metabolic phenotype for neuroendocrine neoplasms (NEN). Twenty-eight patients with NEN were prospectively recruited: small bowel NEN, n = 8; pancreatic NEN, n = 10; and others, n = 10 (mean age 49.4 years [26–81] male/female ratio 17:11). There were 17 healthy control patients. Urine samples were subjected to 1H nuclear magnetic resonance spectroscopic profiling via the use of a Bruker Avance 600-MHz spectrometer (Bruker, Rheinstetten, Germany). Acquired spectral data were imported into SIMCA and MATLAB for supervised and unsupervised multivariate analysis. Partial least squares-discriminant analysis differentiated between NEN and healthy samples with accuracy (R(2)Y = 0.79, Q2Y = 0.53, area under the curve [AUC] 0.90). Orthogonal partial least squares-discriminant analysis was able to distinguish between small bowel NEN and pancreatic NEN (R2Y = 0.91, Q2Y = 0.35). Subclass analysis also demonstrated class separation between functional and nonfunctional NEN (R2Y = 0.98, Q2Y = 0.77, AUC 0.6) and those with metastases (R2Y = 0.72 , Q2 Y = 0.41, AUC 0.86) due to variations in hippurate metabolism (P analysis suggests that subgroups of NEN may possess a stratified metabolic phenotype. Metabolic profiling could provide novel biomarkers for NEN.

  15. Neuroendocrine Liver Metastases and Orthotopic Liver Transplantation: The US Experience

    Directory of Open Access Journals (Sweden)

    N. Thao T. Nguyen

    2011-01-01

    Full Text Available Liver transplantation remains a controversial therapy for Neuroendocrine liver metastases (NLM, with coflicting suvival data reported. The aim was to assess the evolution of outcomes for patients transplanted for NLM in the US, both before and after the introduction of the MELD scoring system in 2002. The UNOS/OPTN database was reviewed to identify patients diagnosed with NLM who subsequently underwent a liver transplantation from 1988 to March 2011 (=184; Patient survival was determined using Kaplan-Meier methods and log-rank tests, and cox regression analysis was performed, using SPSS 15.0 (SPSS, Inc, Chicago, IL. The overall NLM patient survivals in the pre-MELD era were 79.5%, 61.4%, and 49.2% at 1, 3, and 5 years, respectively. After the introduction of the MELD score, NET/NLM patients had improved overall patient survivals at 1, 3, and 5 years of 84.7%, 65%, and 57.8%. Patients transplanted after 2002 had an improved survival outcome. Notably, the overall patient survival for NET is not significantly different when compared to the outcomes of patients transplanted for HCC, in the current era. This progress acknowleges the significant improvement in outcomes for NLM patients after liver transplantation and the potential for further gain in the survival of otherwise nonsurgical, terminal patients.

  16. Occupational doses in neuroendocrine tumors by using 177Lu DOTATATE

    International Nuclear Information System (INIS)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de

    2011-01-01

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of 177 Lu DOTATATE radiopharmaceutical which is a type of treatment presently used in the experimental form in Brazil and, therefore, not contemplated in norms or specific use. This research studied the occupational doses of this treatment and suggested guidelines or rules of procedures viewing the radiological protection of workers involved and the public. The treatment were followed up by using two types of radiation detection, one a scintillator and a Geiger-Muller, and the measurements were performed in a public hospital at Rio de Janeiro and the other in a private hospital at Sao Paulo. It was observed that the equivalent occupational doses can variate from 160 μSv to 450 μSv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 μSv/h

  17. Neuroendocrine effects of endocrine disruptors in teleost fish.

    Science.gov (United States)

    Le Page, Yann; Vosges, Mélanie; Servili, Arianna; Brion, François; Kah, Olivier

    2011-01-01

    Because a large proportion of potential endocrine disruptors (EDC) end up in surface waters, aquatic species are particularly vulnerable to their potential adverse effects. Recent studies identified a number of brain targets for EDC commonly present in environmentally relevant concentrations in surface waters. Among those neuronal systems disrupted by EDC are the gonadotropin-releasing hormone (GnRH) neurons, the dopaminergic and serotoninergic circuits, and more recently the Kiss/GPR54 system, which regulates gonadotropin release. However, one of the most striking effects of EDC, notably estrogen mimics, is their impact on the cyp19a1b gene that encodes the brain aromatase isoform in fish. Moreover, this is the only example in which the molecular basis of endocrine disruption is fully understood. The aims of this review were to (1) synthesize the most recent discoveries concerning the EDC effects upon neuroendocrine systems of fish and (2) provide, when possible, the underlying molecular basis of disruption for each system concerned. The potential adverse effects of EDC on neurogenesis, puberty, and brain sexualization are also described. It is important to point out the future environmental, social, and economical issues arising from endocrine disruption studies in the context of risk assessment.

  18. Pancreatic neuroendocrine tumours: correlation between MSCT features and pathological classification

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yanji; Dong, Zhi; Li, Zi-Ping; Feng, Shi-Ting [The First Affiliated Hospital, Sun Yat-Sen University, Department of Radiology, Guangzhou, Guangdong (China); Chen, Jie [The First Affiliated Hospital, Sun Yat-Sen University, Department of Gastroenterology, Guangzhou, Guangdong (China); Chan, Tao; Chen, Minhu [Union Hospital, Hong Kong, Medical Imaging Department, Shatin, N.T. (China); Lin, Yuan [The First Affiliated Hospital, Sun Yat-Sen University, Department of Pathology, Guangzhou, Guangdong (China)

    2014-11-15

    We aimed to evaluate the multi-slice computed tomography (MSCT) features of pancreatic neuroendocrine neoplasms (P-NENs) and analyse the correlation between the MSCT features and pathological classification of P-NENs. Forty-one patients, preoperatively investigated by MSCT and subsequently operated on with a histological diagnosis of P-NENs, were included. Various MSCT features of the primary tumour, lymph node, and distant metastasis were analysed. The relationship between MSCT features and pathologic classification of P-NENs was analysed with univariate and multivariate models. Contrast-enhanced images showed significant differences among the three grades of tumours in the absolute enhancement (P = 0.013) and relative enhancement (P = 0.025) at the arterial phase. Univariate analysis revealed statistically significant differences among the tumours of different grades (based on World Health Organization [WHO] 2010 classification) in tumour size (P = 0.001), tumour contour (P < 0.001), cystic necrosis (P = 0.001), tumour boundary (P = 0.003), dilatation of the main pancreatic duct (P = 0.001), peripancreatic tissue or vascular invasion (P < 0.001), lymphadenopathy (P = 0.011), and distant metastasis (P = 0.012). Multivariate analysis suggested that only peripancreatic tissue or vascular invasion (HR 3.934, 95 % CI, 0.426-7.442, P = 0.028) was significantly associated with WHO 2010 pathological classification. MSCT is helpful in evaluating the pathological classification of P-NENs. (orig.)

  19. Outcome and CT differentiation of gallbladder neuroendocrine tumours from adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae-Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital and Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lee, Kyoung Boon [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-02-15

    To retrospectively investigate clinical outcome and differential CT features of gallbladder (GB) neuroendocrine tumours (NETs) from adenocarcinomas (ADCs). Nineteen patients with poorly-differentiated (PD) NETs and 19 patients with PD ADCs were enrolled. Clinical outcome was compared by the Kaplan-Meier method. We assessed qualitative and quantitative CT features to identify significant differential CT features of PD NETs from ADCs using univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was used for quantitative CT features. PD NETs showed poorer prognosis with significantly shorter median survival days than ADCs (363 vs. 590 days, P = 0.03). On univariate analysis, NETs more frequently manifested as GB-replacing type and showed well-defined margins accompanied with intact overlying mucosa. On multivariate analysis, well-defined margin was the sole significant CT differentiator (odds ratio = 27.817, P = 0.045). Maximum size of hepatic and lymph node (LN) metastases was significantly larger in NETs (11.0 cm and 4.62 cm) than ADCs (2.40 cm and 2.41 cm). Areas under ROC curves for tumour-to-mucosa ratio, maximum size of hepatic and LN metastasis were 0.772, 0.932 and 0.919, respectively (P < 0.05). GB PD NETs show poorer prognosis than ADCs. Well-defined margin, larger hepatic and LN metastases are useful CT differentiators of GB NETs from ADCs. (orig.)

  20. Meta-type analysis of dopaminergic effects on gene expression in the neuroendocrine brain of female goldfish

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2012-11-01

    Full Text Available Dopamine (DA is a major neurotransmitter important for neuroendocrine control and recent studies have described genomic signalling pathways activated and inhibited by DA agonists and antagonists in the goldfish brain. Here we perform a meta-type analysis using microarray datasets from experiments conducted with female goldfish to characterize the gene expression responses that underlie dopaminergic signalling. Sexually mature, pre-spawning (GSI 4.5 ± 1.3% or sexually regressing ( GSI 3 ± 0.4% female goldfish (15-40 g injected intraperitoneally with either SKF 38393, LY 171555, SCH 23390, sulpiride, or a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and α-methyl-p-tyrosine. Microarray meta-type analysis identified 268 genes in the telencephalon and hypothalamus as having reciprocal (i.e. opposite between agonism and antagonism/depletion fold change responses, suggesting that these transcripts are likely targets for DA-mediated regulation. Noteworthy genes included ependymin, vimentin, and aromatase, genes that support the significance of DA in neuronal plasticity and tissue remodelling. Sub-network enrichment analysis (SNEA was used to identify common gene regulators and binding proteins associated with the differentially expressed genes mediated by DA. SNEA analysis identified gene expression targets that were related to three major categories that included cell signalling (STAT3, SP1, SMAD, Jun/Fos, immune response (IL6, IL1β, TNFs, cytokine, NF-κB, and cell proliferation and growth (IGF1, TGFβ1. These gene networks are also known to be associated with neurodegenerative disorders such as Parkinsons’ disease, well-known to be associated with loss of dopaminergic neurons. This study identifies genes and networks that underlie DA signalling in the vertebrate CNS and provides targets that may be key neuroendocrine regulators. The results provide a foundation for future work on dopaminergic regulation of gene expression in fish

  1. A systematic review and meta-analysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix.

    Science.gov (United States)

    Castle, Philip E; Pierz, Amanda; Stoler, Mark H

    2018-02-01

    There remains uncertainty about the role of human papillomavirus (HPV) infection in causing small-cell neuroendocrine carcinoma (SCNC) and large-cell neuroendocrine carcinoma (LCNC) of the cervix. To clarify the role of HPV in the development of SCNC and LCNC, we conducted a systematic review and meta-analyses. PubMed and Embase were searched to initially identify 143 articles published on or before June 1, 2017. Studies were limited to methods that tested for HPV in the cancer tissue directly to minimize misattribution. Thirty-two studies with 403 SCNC and 9 studies of 45 LCNC were included in the analysis. For SCNC, 85% (95% confidence interval [95%CI]=71%-94%) were HPV positive, 78% (95%CI=64%-90%) were HPV16 and/or HPV18 positive, 51% (95%CI=39%-64%) were singly HPV18 positive, and 10% (95%CI=4%-19%) were singly HPV16 positive. In a subset of 5 SCNC studies (75 cases), 93% were positive for p16 INK4a by immunohistochemistry and 100% were HPV positive. For LCNC, 88% (95%CI=72%-99%) were HPV positive, 86% (95%CI=70%-98%) were positive for HPV16 or HPV18, 30% were singly HPV18 positive (95%CI=4%-60%), and 29% (95%CI=2%-64%) were singly HPV16 positive. In conclusion, most SCNC and LCNC are caused by HPV, primarily HPV18 and HPV16. Therefore, most if not all SCNC and LCNC will be prevented by currently available prophylactic HPV vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Directory of Open Access Journals (Sweden)

    Patricia Blanchet

    2017-08-01

    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  3. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

    NARCIS (Netherlands)

    F.R.E. Nobels (Frank); D.J. Kwekkeboom (Dirk Jan); W. Coopmans; C.H.H. Schoenmakers (Christian); J. Lindemans (Jan); E.P. Krenning (Eric); R. Bouillon (Roger); S.W.J. Lamberts (Steven); W.W. de Herder (Wouter)

    1997-01-01

    textabstractChromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other

  4. Poorly-differentiated colorectal neuroendocrine tumour: CT differentiation from well-differentiated neuroendocrine tumour and poorly-differentiated adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ji Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-09-15

    The differentiation of poorly-differentiated neuroendocrine tumours (PD-NETs), well-differentiated NETs (WD-NETs), and adenocarcinomas (ADCs) is important due to different management options and prognoses. This study is to find the differential CT features of colorectal PD-NETs from WD-NETs and ADCs. CT features of 25 colorectal WD-NETs, 36 PD-NETs, and 36 ADCs were retrospectively reviewed. Significant variables were assessed using univariate and multivariate analyses. Receiver operating characteristics analysis determined the optimal cut-off value of tumour and lymph node (LN) size. Large size, rectum location, ulceroinfiltrative morphology without intact overlying mucosa, heterogeneous attenuation with necrosis, presence of ≥3 enlarged LNs, and metastasis were significant variables to differentiate PD-NETs from WD-NETs (P < 0.05). High attenuation on arterial phase, persistently high enhancement pattern, presence of ≥6 enlarged LNs, large LN size, and wash-in/wash-out enhancement pattern of liver metastasis were significant variables to differentiate PD-NETs from ADCs (P < 0.05). Compared to WD-NETs, colorectal PD-NETs are usually large, heterogeneous, and ulceroinfiltrative mass without intact overlying mucosa involving enlarged LNs and metastasis. High attenuation on arterial phase, presence of enlarged LNs with larger size and greater number, and wash-in/wash-out enhancement pattern of liver metastasis can be useful CT discriminators of PD-NETs from ADCs. (orig.)

  5. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society.

    Science.gov (United States)

    Howe, James R; Cardona, Kenneth; Fraker, Douglas L; Kebebew, Electron; Untch, Brian R; Wang, Yi-Zarn; Law, Calvin H; Liu, Eric H; Kim, Michelle K; Menda, Yusuf; Morse, Brian G; Bergsland, Emily K; Strosberg, Jonathan R; Nakakura, Eric K; Pommier, Rodney F

    2017-07-01

    Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.

  6. CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

    2015-07-15

    To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

  7. Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation.

    Directory of Open Access Journals (Sweden)

    Francesco Giovinazzo

    Full Text Available Chromogranin A is a neuroendocrine secretory product and its loss is a feature of malignant NEN de-differentiation. We hypothesized that chromogranin A fragments were differentially expressed during NEN metastasis and played a role in the regulation of NEN proliferation.Chromogranin A mRNA (PCR and protein (ELISA/western blot were studied in 10 normal human mucosa, 5 enterochromaffin cell preparations, 26 small intestinal NEN primaries and 9 liver metastases. Cell viability (WST-1 assay, proliferation (bromodeoxyuridine ELISA and expression of AKT/AKT-P (CASE ELISA/western blot in response to chromogranin A silencing, inhibition of prohormone convertase and mTOR inhibition (RAD001/AKT antisense as well as different chromogranin A fragments were examined in 4 SI-NEN cell lines.Chromogranin A mRNA and protein levels were increased (37-340 fold, p<0.0001 in small intestinal NENs compared to normal enterochromaffin cells. Western blot identified chromogranin A-associated processing bands including vasostatin in small intestinal NENs as well as up-regulated expression of prohormone convertase in metastases. Proliferation in small intestinal NEN cell lines was decreased by silencing chromogranin A as well as by inhibition of prohormone convertase (p<0.05. This inhibition also decreased secretion of chromogranin A (p<0.05 and 5-HT (p<0.05 as well as expression of vasostatin. Metastatic small intestinal NEN cell lines were stimulated (50-80%, p<0.05 and AKT phosphorylated (Ser473: p<0.05 by vasostatin I, which was completely reversed by RAD001 (p<0.01 and AKT antisense (p<0.05 while chromostatin inhibited proliferation (~50%, p<0.05.Chromogranin A was differentially regulated in primary and metastatic small intestinal NENs and cell lines. Chromogranin A fragments regulated metastatic small intestinal NEN proliferation via the AKT pathway indicating that CgA plays a far more complex role in the biology of these tumors than previously considered.

  8. Image Findings of a Rare Case of Neuroendocrine Tumor Metastatic to Orbital Extraocular Muscle in Gallium-68 DOTANOC Positron Emission Tomography/Computed Tomography and Therapy with Lutetium-177 DOTATATE

    OpenAIRE

    Kamaleshwaran, Koramadai Karuppusamy; Joseph, Jephy; Upadhya, Indra; Shinto, Ajit Sugunan

    2017-01-01

    Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1-13% of all orbital masses. In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit, followed by metastasis from the lung, prostate, and gastrointestinal tract. Carcinoid tumors are rare neuroendocrine neoplasms derived from enterochromaffin cells, which are found primarily in the gastrointestinal tract and bronchial tree. Liver metastases are the...

  9. Thymomas: a cytological and immunohistochemical study, with emphasis on lymphoid and neuroendocrine markers

    Directory of Open Access Journals (Sweden)

    Burke Allen P

    2007-05-01

    Full Text Available Abstract Background The current study correlates cytologic morphology with histologic type and describes immunophenotypes with a focus on epithelial, neuroendocrine, and lymphoid characteristics in an institutional series of surgically excised thymomas. Methods Fine needle aspirates (FNAs and surgical specimens were retrospectively analyzed, and immunohistochemical stains were performed for EMA, cytokeratin 7, cytokeratin 20, CD57 CD5, bcl-2, calretinin, vimentin, CD3, CD20, CD1a, CD99 and Ki67. Tumors were classified by WHO criteria. Results There were eleven male and six female patients with an age range of 41 to 84 years (mean, 61 years and a male to female ratio of 1.8:1. Four thymomas (4/17, 23.5% were associated with neuromuscular disease: myasthenia gravis (n = 3 and limbic encephalitis (n = 1. FNA, under CT guidance, was performed in 7 cases. The positive predictive value for thymoma by FNA cytology was 100% and the sensitivity was 71%. Thymomas associated with neuromuscular disorders were WHO types B2 (n = 1 and B3 (n = 3, and showed a strong expression of CD57 in the majority of neoplastic epithelial cells accompanied by large numbers of CD20+ intratumoral B lymphocytes. Two of seventeen (11.7% thymomas (all sporadic B3 type contained numerous neoplastic epithelial cells positive for CD5 and bcl-2. Conclusion Our results suggest that thymomas associated with autoimmune disorders contain a significant population of CD20+ intratumoral B lymphocytes. Strong CD57 positivity in thymomas may suggest a concomitant neuromuscular disorder, notably myasthenia gravis. CD5 expression is of limited value in the differential diagnosis of primary thymic epithelial neoplasms since both thymic carcinomas and thymomas may express CD5.

  10. Small cell carcinoma of the vulva: case report

    Directory of Open Access Journals (Sweden)

    Ana Correia

    2017-04-01

    Full Text Available Neuroendocrine tumours are rare in the gynaecologic tract, comprising approximately 2% of all gynaecological tumours. They have an aggressive behaviour and are a diagnostic and clinical challenge, due to their rarity and the lack of standardized therapeutic approaches. There are a few case reports. It is defined as a high-grade carcinoma exhibiting neuroendocrine differentiation. The authors describe the case of a 70-year-old woman, with vulvar neuroendocrine small cell carcinoma after superficial vulvectomy. The patient was submitted to a surgery with wide local excision and adjuvant radiation therapy. A review of the literature on this topic is also presented.

  11. Detection of human neuronal α7 nicotinic acetylcholine receptors by conjugates of snake α-neurotoxin with quantum dots.

    Science.gov (United States)

    Makarova, Ya V; Shelukhina, I V; Mukherjee, A K; Kuznetsov, D V; Tsetlin, V I; Utkin, Yu N

    2017-07-01

    Fluorescent derivatives are widely used to study the structure and functions of proteins. Quantum dots (QDs), fluorescent semiconductor nanocrystals, have a high quantum yield and are much more resistant to bleaching compared to organic dyes. Conjugates of α-neurotoxins with QDs were used for visualization of human α7 acetylcholine receptors heterologously expressed in GH4C1 pituitary adenoma cells. Specific staining of cells by the conjugated toxins was observed.

  12. Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours

    DEFF Research Database (Denmark)

    Yadegarfar, G; Friend, L; Jones, Leigh Robert

    2013-01-01

    Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours.......Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours....

  13. Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Damholt, M B; Christensen, N J; Hilsted, Jannik

    2001-01-01

    Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes...... within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i...... in neuroendocrine responses occur early in the course of diabetes, we investigated the responses to insulin-induced hxypoglycaemia during the first year of type 1 diabetes. Autonomic and somatic nerve function tests were performed concomitantly. Six type 1 diabetes patients were studied 3 and 12 months after...

  14. Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining...... for neuroendocrine markers and the fact that NCB may only show slight neuroendocrine morphology that can easily be overlooked, NCB is often underdiagnosed. Consequently, there is a need for fast and reliable detection method for NCB. Here, we take a first step toward finding an easy way of identifying NCB...... by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained...

  15. Endoscopic ultrasound-guided ethanol ablation of pancreatic neuroendocrine tumours: A case study and literature review.

    Science.gov (United States)

    Armellini, Elia; Crinò, Stefano F; Ballarè, Marco; Pallio, Socrate; Occhipinti, Pietro

    2016-02-10

    Here we offer a review of the literature regarding endoscopic ultrasound-guided ethanol ablation for pancreatic neuroendocrine tumours and describe the case of a cystic tumour completely ablated after a multisession procedure. A total of 35 PubMed indexed cases of treated functioning and non-functioning pancreatic neuroendocrine tumours resulted from our search, 29 of which are well-documented and summarised. Endoscopic ultrasound-guided ethanol ablation appears as a local, minimally invasive treatment of pancreatic neuroendocrine tumours, suitable for selected patients. This technique appears feasible, relatively safe and efficient, especially when applied to symptom relief in functioning tumours, aiming at loss of endocrine secretion. For non-functioning tumours, where the goal is complete tissue ablation, eus guided ethanol ablation can provide good results for patients who are unfit for surgery or for those who refuse surgical resection. Its role in "fit for surgery" patients requires assessment through further studies.

  16. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Norsk, Peter; Gustafsson, Finn

    2005-01-01

    inhibitors and beta-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady......Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme......-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure...

  17. A Rare Case of Primary Infiltrating Neuroendocrine Carcinoma of the Breast

    International Nuclear Information System (INIS)

    Nawawi, Ouzreiah; Ying Goh, Keat; Rahmat, Kartini

    2012-01-01

    Primary neuroendocrine carcinoma of the breast is a very rare malignant tumor. There are not many cases reported in the English literature since it was first documented in 1983. Reports on the imaging features, in particular the ultrasonographic features of this rare tumor are scarce. Herein, we report a case of aggressive primary infiltrating neuroendocrine carcinoma of the breast, masquerading as an inflammatory breast condition in a 22-year-old young lady, perhaps the youngest case ever reported in the English literature. We discuss the imaging features and highlight the Doppler ultrasonographic findings of this rare breast carcinoma. This is the first documentation on Doppler ultrasonographic findings of primary neuroendocrine carcinoma of the breast in the literature

  18. Psychological, cultural and neuroendocrine profiles of risk for preterm birth.

    Science.gov (United States)

    Ruiz, R Jeanne; Dwivedi, Alok Kumar; Mallawaarachichi, Indika; Balcazar, Hector G; Stowe, Raymond P; Ayers, Kimberly S; Pickler, Rita

    2015-09-03

    Preterm birth remains a major obstetrical problem and identification of risk factors for preterm birth continues to be a priority in providing adequate care. Therefore, the purpose of this study was to elucidate risk profiles for preterm birth using psychological, cultural and neuroendocrine measures. From a cross sectional study of 515 Mexican American pregnant women at 22-24 weeks gestation, a latent profile analysis of risk for preterm birth using structural equation modeling (SEM) was conducted. We determined accurate gestational age at delivery from the prenatal record and early ultrasounds. We also obtained demographic and prenatal data off of the chart, particularly for infections, obstetrical history, and medications. We measured depression (Beck Depression Inventory), mastery (Mastery scale), coping (The Brief Cope), and acculturation (Multidimensional Acculturation Scale) with reliable and valid instruments. We obtained maternal whole blood and separated it into plasma for radioimmunoassay of Corticotrophin Releasing Hormone (CRH). Delivery data was obtained from hospital medical records. Using a latent profile analysis, three psychological risk profiles were identified. The "low risk" profile had a 7.7% preterm birth rate. The "moderate risk" profile had a 12% preterm birth rate. The "highest risk" profile had a 15.85% preterm birth rate. The highest risk profile had double the percentage of total infections compared to the low risk profile. High CRH levels were present in the moderate and highest risk profiles. These risk profiles may provide a basis for screening for Mexican American women to predict risk of preterm birth, particularly after they are further validated in a prospective cohort study. Future research might include use of such an identified risk profile with targeted interventions tailored to the Hispanic culture.

  19. Peptide receptor radionuclide therapy with somatostatin analogues in neuroendocrine tumors.

    Science.gov (United States)

    Giovacchini, Giampiero; Nicolas, Guillaume; Forrer, Flavio

    2012-06-01

    Neuroendocrine tumors (NETs) are rare tumors with variable malignant behavior. The majority of NETs express increased levels of somatostatin (SST) receptors, particularly SST2 receptors. Radiolabeled peptides specific for the SST2 receptors may be used for diagnosis of NETs and for peptide receptor radionuclide therapy (PRRT). [(111)In-DTPA(0)]-octreotide has been the first peptide used for PRRT. This radiolabeled peptide, emitting Auger electrons, often induced symptomatic relief, but objective morphological responses were rarely documented. After the introduction of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) other peptides, primarily [DOTA(0),Tyr(3)]octreotate (DOTATATE) and [DOTA(0),Tyr(3)]octreotide (DOTATOC) were labeled with (90)Y or (177)Lu and used for therapy applications. The rate of objective response obtained with these radiolabeled peptides ranges between 6% and 46%, owing to differences in inclusion criteria adopted in different studies, length and type of therapy, and criteria of evaluation of the response. The present data in the literature do not allow defining the most suitable peptide and radionuclide for the treatment of NETs. Instead emerging evidence indicates that a combination of nuclides with different physical characteristics might be more effective than the use of a single nuclide. Kidney and bone marrow toxicity are the limiting factors for PRRT. Mild toxicity is often encountered while severe toxicity is rarer. Toxicity could be reduced and therapeutic efficacy enhanced by patient-specific dosimetry. Future directions include different issues of PRRT, such as defining the most suitable treatment scheme, evaluation of new peptides with different affinity profiles to other SST receptor subtypes, and reduction of toxicity.

  20. Lu-177 DOTATATE dosimetry for neuroendocrine tumor: single center experience

    Science.gov (United States)

    Said, MA; Masud, MA; Zaini, MZ; Salleh, RA; Lee, BN; Zainon, R.

    2017-05-01

    Lu-177 labelled with DOTATE is widely acceptable to treat Neuroendocrine Tumor (NET) disease and it better improvement of quality of patients’ life since few years ago. However, the radionuclide toxicity becomes the main limitation of the (NET) treatment. Therefore, we performed a pilot study aimed to estimate radiation absorbed doses to dose-limiting organs to develop a systemic therapy with Lu-177 in NET patients. In this study, five set of planar whole body images was acquired every 0.5 hour, 4 hours, 24 hours, 48 hours and 72 hours after Lu-177 administrations. The planar image acquisition was done using Philip Brightview X with Medium Energy General Purpose Collimator (MEGP) collimator. All patients’ images in Conjugate View (CV) format were transferred into PMOD 3.7 Software for Region of Interest (ROI) analysis. The ROI were drawn at selected organs such as kidneys, liver, spleen and bladder. This study found that the mean absorbed dose for kidneys 0.62 ± 0.26 Gy/GBq, liver 0.63 ± 0.28 Gy/GBq, spleen 0.83 ± 0.73 Gy/GBq and bladder 0.14 ± 0.07 Gy/GBq. The radionuclide kinetic for the whole body 99.7 ± 0.1 percent at 0.5 hours, 79.5 ± 10.7 percent at 4 hours, 56.6 ± 10.3 percent at 24 hours, 43.2 ± 7.9 percent at 48 hours and 37.1 ± 9.0 percent at 72 hours. This study verifies that this planar quantitative method able to determine organ at risk and the result line with other published data.

  1. Global microRNA profiling of pancreatic neuroendocrine neoplasias.

    Science.gov (United States)

    Thorns, Chistoph; Schurmann, Claudia; Gebauer, Niklas; Wallaschofski, Henri; Kümpers, Christiane; Bernard, Veronica; Feller, Alfred C; Keck, Tobias; Habermann, Jens K; Begum, Nehara; Lehnert, Hendrik; Brabant, Georg

    2014-05-01

    Pancreatic neuroendocrine neoplasms (pNEN) are rare tumors with a poor prognosis. Although increasing data have accumulated on the molecular pathology of pNEN, very scarce data exist on microRNAs in pNEN and no data are published on microRNAs as potential biomarkers of pNEN in serum. This study aimed to identify microRNA signatures of pNEN in tissue and serum. We included tissue samples from 37 patients with pNEN, 9 patients with non-neoplastic pancreatic pathology, seven samples of micro-dissected pancreatic islets and serum samples of 27 patients with pNEN, as well as of 15 healthy volunteers. MicroRNA expression profiles were established using real-time quantitative Polymerase Chain reaction (PCR) for 754 microRNAs. MicroRNA signatures differed between pNEN, pancreatic islets and total pancreas, with virtually no overlap between the groups of de-regulated microRNAs. Expression of miR-642 correlated with Ki67 (MiB1) score and miR-210 correlated with metastatic disease. When comparing microRNA levels in serum from patients with pNEN and healthy volunteers, 13 microRNAs were more abundant in the serum of patients. MiR-193b was also up-regulated in pNEN tissue when compared to pancreatic islets and remained significantly increased in serum even when corrected for multiple testing. Evaluation of microRNAs appears to be promising in the assessment of pNEN. In particular, miR-193b, which is also increased in serum, may be a potential new biomarker of pNEN.

  2. Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors

    Science.gov (United States)

    Yang, Jiao-Jiao; Huang, Hua; Xiao, Ming-Bing; Jiang, Feng; Ni, Wen-Kai; Ji, Yi-Fei; Lu, Cui-Hua; Ni, Run-Zhou

    2017-01-01

    Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry. Strong SCML2 staining was observed predominantly in the cell nuclei of GEP-NET tissues, and the overall expression rate and staining intensity of SCML2 were higher than those of Syn or CgA, respectively. Spearman rank correlation analysis demonstrated that SCML2 was not correlated with either Syn or CgA, while the combined detection of SCML2 with Syn or with CgA increased the diagnostic sensitivity to 100%. SCML2 expression in GEP-NETs was associated with several clinicopathological parameters, such as histological type, tumor grade, depth of invasion and clinical stage. Kaplan-Meier survival curves revealed that patients with higher SCML2 expression had lower survival rates than those with lower expression levels, while Cox proportional hazards regression analysis revealed that SCML2 was not an independent prognostic factor for GEP-NET patients. Therefore, SCML2 may have potential as a specific marker for joint use with other markers to improve the diagnostic efficiency of GEP-NETs. PMID:28810646

  3. A neuroendocrine mechanism of co-morbidity of depression-like behavior and myocardial injury in rats.

    Directory of Open Access Journals (Sweden)

    Wang Xinxing

    Full Text Available Depression is generally a recurrent psychiatric disorder. Evidence shows that depression and cardiovascular diseases are common comorbid conditions, but the specific pathological mechanisms remain unclear. The purpose of this study is to determine the effects of depression induced by chronic unpredictable mild stress (CUMS on myocardial injury and to further elucidate the biological mechanism of depression. Rats were used as a model. The CUMS procedure lasted for a total of 8 weeks. After 4 weeks of CUMS, treated rats exhibited a reduced sucrose preference and changes in scores on an open field test, body weight and content of 5-HT in the brain as compared with the values of these variables in controls. These changes indicated depression-like changes in CUMS rats and demonstrated the feasibility of the depression model. In addition, pathological changes in the myocardium and increased cardiomyocyte apoptosis demonstrated that myocardial injury had occurred after 6 weeks of CUMS and had increased significantly by the end of 8 weeks of CUMS. Plasma serotonin (5-HT, norepinephrine (NE and epinephrine (E, all depression-related neuroendocrine factors, were measured by HPLC-ECD techniques, and the content of plasma corticosterone (GC was evaluated by an I(125-cortisol radioactivity immunoassay in control and CUMS rats. The results indicated that 5-HT had decreased, whereas NE, E and GC had increased in CUMS rats, and these factors might be associated with depression-induced myocardial injury. The effects of 5-HT, NE and GC on the survival rate of cultured cardiomyocytes were determined using an orthogonal design. The results showed that 5-HT was a more important factor affecting cell survival than GC or NE. The results suggested that normal blood levels of 5-HT had a cytoprotective effect. The neuroendocrine disorders characterized by decreased 5-HT combined with increased GC and NE mediated the occurrence of depression-induced myocardial injury.

  4. Goblet cell carcinoids

    DEFF Research Database (Denmark)

    Olsen, Ingrid Holst; Holt, Nanna; Langer, Seppo W

    2015-01-01

    BACKGROUND: Appendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features. PATIENTS AND METHODS: Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27) diagnosed 1992-2013. RESULTS: Median age for f/m was 59...

  5. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

    Science.gov (United States)

    Kaemmerer, Daniel; Prasad, Vikas; Daffner, Wolfgang; Hörsch, Dieter; Klöppel, Günter; Hommann, Merten; Baum, Richard P

    2009-01-01

    Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis many of them are already advanced and difficult to treat. We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman, who received neoadjuvant peptide receptor radionuclide therapy (PRRT) as first-line treatment. This resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal. Follow-up for eighteen months revealed a complete remission. This is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection. PMID:19998512

  6. The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Federspiel, Birgitte; Agersnap, Mikkel

    2016-01-01

    OBJECTIVE: Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma...... syndrome in man has remained unknown until now. MATERIAL AND METHODS: Using a panel of immunoassays for CCK peptides and proCCK as well as for chromogranin A, we have examined plasma samples from 284 fasting patients with gastroenteropancreatic neuroendocrine tumors. In hyperCCKemic samples, plasma CCK...

  7. Primary Neuroendocrine Breast Carcinoma in a 13-Year-Old Girl: Ultrasonography and Pathology Findings

    Directory of Open Access Journals (Sweden)

    Mazamaesso Tchaou

    2017-01-01

    Full Text Available Neuroendocrine carcinoma (NEC of the breast is a rare disease and has been scarcely reported by African authors. The authors report a case of breast NEC in a 13-year-old African girl initially diagnosed as an atypical adenofibroma by ultrasonography. Ultrasound-guided biopsy and conventional histological examination indicated two potential diagnoses: primary malignant non-Hodgkin’s lymphoma and undifferentiated carcinoma. According to immunohistochemistry performed on paraffin blocks in France, infiltrating ductal carcinoma with a strong neuroendocrine component was confirmed by CD56, CD57, and chromogranin A markers.

  8. Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection.

    Science.gov (United States)

    Wunder, T; Schmid, K; Wicklein, D; Groitl, P; Dobner, T; Lange, T; Anders, M; Schumacher, U

    2013-01-01

    Coxsackie adenovirus receptor (CAR) is the primary receptor to which oncolytic adenoviruses have to bind for internalization and viral replication. A total of 171 neuroendocrine lung tumors in form of multitissue arrays have been analyzed resulting in a positivity of 112 cases (65.5%). Immunostaining correlated statistically significant with histopathology and development of recurrence. The subtype small cell lung cancer (SCLC) showed the highest CAR expression (77.6%), moreover the CAR level was correlated to the disease-free survival. Further, high CAR expression level in SCLC cell lines was found in vitro and in vivo when cell lines had been transplanted into immunodeficient mice. A correlation between CAR expression in the primary tumors and metastases development in the tumor model underlined the clinical relevance. Cell lines with high CAR level showed a high infectivity when infected with a replication-deficient adenovirus. Low levels of CAR expression in SCLC could be upregulated with Trichostatin A, a histone deacetylase inhibitor. As a result of the unaltered poor prognosis of SCLC and its high CAR expression it seems to be the perfect candidate for oncolytic therapy. With our clinically relevant tumor model, we show that xenograft experiments are warrant to test the efficiency of oncolytic adenoviral therapy.

  9. Circadian Tick-Talking Across the Neuroendocrine System and Suprachiasmatic Nuclei Circuits: The Enigmatic Communication Between the Molecular and Electrical Membrane Clocks.

    Science.gov (United States)

    Belle, M D C

    2015-07-01

    As with many processes in nature, appropriate timing in biological systems is of paramount importance. In the neuroendocrine system, the efficacy of hormonal influence on major bodily functions, such as reproduction, metabolism and growth, relies on timely communication within and across many of the brain's homeostatic systems. The activity of these circuits is tightly orchestrated with the animal's internal physiological demands and external solar cycle by a master circadian clock. In mammals, this master clock is located in the hypothalamic suprachiasmatic nucleus (SCN), where the ensemble activity of thousands of clock neurones generates and communicates circadian time cues to the rest of the brain and body. Many regions of the brain, including areas with neuroendocrine function, also contain local daily clocks that can provide feedback signals to the SCN. Although much is known about the molecular processes underpinning endogenous circadian rhythm generation in SCN neurones and, to a lesser extent, extra-SCN cells, the electrical membrane clock that acts in partnership with the molecular clockwork to communicate circadian timing across the brain is poorly understood. The present review focuses on some circadian aspects of reproductive neuroendocrinology and processes involved in circadian rhythm communication in the SCN, aiming to identify key gaps in our knowledge of cross-talk between our daily master clock and neuroendocrine function. The intention is to highlight our surprisingly limited understanding of their interaction in the hope that this will stimulate future work in these areas. © 2015 The Author. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of The British Society for Neuroendocrinology.

  10. Labeling of the peptide DOTA-tyr3-octreotate with radioiodine and biodistribution and AR42J neuroendocrine tumor affinity study in mice

    International Nuclear Information System (INIS)

    Nagamati, Lucio Takeshi

    2006-01-01

    Neuroendocrine tumors are rare and affect mainly the gastrointestinal tract but other systems are also affected like the skin, lungs and the nervous system. They are rich in type 2 somatostatin (SM) receptors (SSTR2) and may secrete hormones in excess. Synthetic SM derivative peptides are of great utility because presented bigger half life when compared to SM and can be used to clinical improvement of these patients due to its tumoral inhibitory action. The labeling of these peptides with radioisotopes allowed the acquisition of images with favourable cost-efficiency relationship and use in therapy. The peptide, DOTATyr3- octreotate (DOTATATE), has much more affinity for the SSTR2 receptor than the peptide commercially used nowadays, is easily radioiodinated and has a favourable biodistribution for diagnosis and treatment due to the presence of the chelator DOTA. We have studied the influence of various factors on the radiochemical purity of the labeled compound as labeling stability, absorbed dose estimation and biodistribution in normal and AR42J cell tumor-bearing Swiss and Nude mice. We observed easy and stable peptide radioiodination at peptide/radioiodine ( 131 I) ratio of 2.73 that produced a radiochemical species with retention time of 22.7 minutes at high performance liquid chromatography and presented a favourable biodistribution and dosimetry for imaging and therapy of patients with neuroendocrine tumors, just the opposite result observed the radioiodinated compounds without a chelator as described in the literature. Other molar peptide/radioiodine ratios did not showed good results, with various radiochemical species and unfavourable biodistribution. A possible dosimetric study in patients with neuroendocrine tumors may be carried out in the near future. (author)

  11. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

    Science.gov (United States)

    Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

    2008-10-01

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

  12. Are patients with autoimmune thyroid disease and autoimmune gastritis at risk of gastric neuroendocrine neoplasms type 1?

    Science.gov (United States)

    Alexandraki, Krystallenia I; Nikolaou, Argiro; Thomas, Dimitrios; Syriou, Vassiliki; Korkolopoulou, Penelope; Sougioultzis, Stavros; Kaltsas, Gregory

    2014-05-01

    The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease. Prospective observational study in a single institutional study. One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured. One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up. Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications. © 2013 John Wiley & Sons Ltd.

  13. Most high-grade neuroendocrine tumours of the lung are likely to secondarily develop from pre-existing carcinoids: innovative findings skipping the current pathogenesis paradigm.

    Science.gov (United States)

    Pelosi, Giuseppe; Bianchi, Fabrizio; Dama, Elisa; Simbolo, Michele; Mafficini, Andrea; Sonzogni, Angelica; Pilotto, Sara; Harari, Sergio; Papotti, Mauro; Volante, Marco; Fontanini, Gabriella; Mastracci, Luca; Albini, Adriana; Bria, Emilio; Calabrese, Fiorella; Scarpa, Aldo

    2018-02-01

    Among lung neuroendocrine tumours (Lung-NETs), typical carcinoid (TC) and atypical carcinoid (AC) are considered separate entities as opposed to large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). By means of two-way clustering analysis of previously reported next-generation sequencing data on 148 surgically resected Lung-NETs, six histology-independent clusters (C1 → C6) accounting for 68% of tumours were identified. Low-grade Lung-NETs were likely to evolve into high-grade tumours following two smoke-related paths. Tumour composition of the first path (C5 → C1 → C6) was coherent with the hypothesis of an evolution of TC to LCNEC, even with a conversion of SCLC-featuring tumours to LCNEC. The second path (C4 → C2-C3) had a tumour composition supporting the evolution of AC to SCLC-featuring tumours. The relevant Ki-67 labelling index varied accordingly, with median values being 5%, 9% and 50% in the cluster sequence C5 → C1 → C6, 12% in cluster C4 and 50-60% in cluster C2-C3. This proof-of-concept study suggests an innovative view on the progression of pre-existing TC or AC to high-grade NE carcinomas in most Lung-NET instances.

  14. The development of meta-iodobenzylguanidine analogues for the therapy of neuroendocrine and other tumours

    International Nuclear Information System (INIS)

    Vaidyanathan, G.; Zalutsky, M.R.

    2001-01-01

    Radioiodinated meta-iodobenzylguanidine (MIBG) has been extensively used in the diagnosis and therapy of neuroendocrine tumours such as neuroblastoma. We have developed a no-carrier-added synthesis (n.c.a.) for MIBG as well as other analogues which may improve clinical utility. In SK-N-SH human neuroblastoma cells in vitro, the uptake of n.c.a. [ 131 I]MIBG remained constant over a 2-3-log activity concentration range. In contrast, the uptake of [ 131 I]MIBG prepared by an exchange radioiodination (ex-[ 131 I]MIBG) steadily decreased over the same range demonstrating the saturability of uptake under these conditions. Similar differences in uptake were seen in normal mouse heart and adrenals, the normal target tissues for MIBG. While no advantage of n.c.a [ 131 I]MIBG over ex-[ 131 I]MIBG was seen in athymic mice hosting SK-N-SH neuroblastoma xenografts, higher tumour uptake and tumour-to-normal tissue ratios were observed when SK-N- BE(2C) xenografts were used. Since neuroblastoma is often associated with micrometastases, an MIBG analogue labelled with the -particle emitting 211 At could be advantageous. A method has been developed for the efficient synthesis of meta-[ 211 At]astatobenzylguanidine (MABG). A number of in vitro assays and tissue distribution studies showed that MABG is an excellent analogue of MIBG. From clonogenic assays using SK-N-SH neuroblastoma cells, it was calculated that the D 0 value for MABG (215 Bq/ml) was more than 1000-fold lower than that of n.c.a. [ 131 I]MIBG. A 18 F-labelled analogue of MIBG, 4-[ 18 F]fluoro-3-iodobenzylguanidine ([ 18 F]FIBG), has been prepared and is shown to have a higher uptake in SK-N-SH cells than MIBG. Because it may be an invaluable tool in combination with [ 18 F]FIBG, a method has been developed for the synthesis of its radioiodinated analogue, [ 131 I]FIBG. It was shown that SK-N-SH cells retained FIBG to a significantly higher degree than MIBG over a 3-day period, suggesting that [ 131 I]FIBG may deliver

  15. Aspectos neuroendocrinos de la obesidad Neuroendocrine aspects of obesity

    Directory of Open Access Journals (Sweden)

    Mario Perello

    2004-06-01

    Full Text Available En la fisiopatología de la obesidad intervienen factores genéticos, sociales, metabólicos, endocrinos y neurológicos. Esta multifactoriedad junto al hecho que estos factores se interrelacionan a través de mecanismos muy complejos, que son sólo parcialmente conocidos, ha llevado a que la comprensión íntima de este trastorno resulte una tarea sumamente ardua. Por estos motivos, el conocimiento integral de esta afección plantea un desafío al que actualmente están abocados numerosos grupos de investigadores. El análisis de la obesidad como un trastorno neuroendocrino, propone el estudio de este fenómeno desde una visión particular que implica disfunciones en casi todos los órganos endocrinos y en el sistema nervioso central, fundamentalmente en la actividad hipotalámica. Estas alteraciones afectan principalmente a los ejes neuroendocrinos hipotálamo-hipofiso-adrenal, adipo-insular y al control hipotalámico, tanto de la ingesta de alimento como del almacenamiento y gasto energético. Este artículo plantea una actualización en este campo; en primer lugar, se realiza una breve descripción, en forma independiente, de los principales sistemas antes mencionados y luego una descripción de su funcionamiento normal integrado. Finalmente, se describen desregulaciones de estos mecanismos y se discute como ellas contribuirían al desarrollo y/o mantenimiento de la obesidad.Genetic, social, metabolic, endocrine and neural events participate in the physiopathological development of obesity. Because of the multifactorial background of obesity, up to now, it has been very difficult to fully understand the whole disease. In fact, the relationship between several signals, through very complex mechanisms, is only partially known. Obesity, from a neuroendocrine point of view, implies taking into account abnormalities in both hypothalamic and endocrine functions. Among altered functions in obesity, namely those involving the hypothalamo

  16. Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study.

    Science.gov (United States)

    Stasi, Cristina; Bellini, Massimo; Gambaccini, Dario; Duranti, Emiliano; de Bortoli, Nicola; Fani, Bernardo; Albano, Eleonora; Russo, Salvatore; Sudano, Isabella; Laffi, Giacomo; Taddei, Stefano; Marchi, Santino; Bruno, Rosa Maria

    2017-07-30

    Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS. Thirty IBS and 30 healthy volunteers were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid, plasma serotonin (5-hydroxytryptamine, 5-HT), endothelin, and neuropeptide Y (NPY), and plasma and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA). Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), 5-HT (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1] pg/mL, P = 0.054], compared to healthy volunteers. Moreover, plasma NPY, endothelin, cortisol and 5-HT, and urinary 5-hydroxyindoleacetic acid were associated with some psychological disorders ( P ≤ 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/min, P = 0.048; +30.1% vs +78.1%, P = 0.023). Baseline MSNA tended to be associated with urinary cortisol ( ρ = 0.557, P = 0.059). Moreover, changes in heart rate after mental stress were associated with urinary cortisol ( ρ = 0.682, P = 0.021) and changes in MSNA after mental stress were associated with plasma cortisol ( ρ = 0.671, P = 0.024)." Higher concentrations of endothelin, NPY, and 5-HT were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy volunteers.

  17. Differentiation in neuroblastoma: diffusion-limited hypoxia induces neuro-endocrine secretory protein 55 and other markers of a chromaffin phenotype.

    Directory of Open Access Journals (Sweden)

    Fredrik Hedborg

    2010-09-01

    Full Text Available Neuroblastoma is a childhood malignancy of sympathetic embryonal origin. A high potential for differentiation is a hallmark of neuroblastoma cells. We have previously presented data to suggest that in situ differentiation in tumors frequently proceeds along the chromaffin lineage and that decreased oxygen (hypoxia plays a role in this. Here we explore the utility of Neuro-Endocrine Secretory Protein 55 (NESP55, a novel member of the chromogranin family, as a marker for this process.Immunohistochemical analyses and in situ hybridizations were performed on human fetal tissues, mouse xenografts of human neuroblastoma cell lines, and on specimens of human neuroblastoma/ganglioneuroma. Effects of anaerobic exposure on gene expression by cultured neuroblastoma cells was analyzed with quantitative real-time PCR. Fetal sympathetic nervous system expression of NESP55 was shown to be specific for chromaffin cell types. In experimental and clinical neuroblastoma NESP55 immunoreactivity was specific for regions of chronic hypoxia. NESP55 expression also correlated strikingly with morphological evidence of differentiation and with other chromaffin-specific patterns of gene expression, including IGF2 and HIF2α. Anaerobic culture of five neuroblastoma cell lines resulted in an 18.9-fold mean up-regulation of NESP55.The data confirms that chronic tumor hypoxia is a key microenvironmental factor for neuroblastoma cell differentiation, causing induction of chromaffin features and NESP55 provides a reliable marker for this neuronal to neuroendocrine transition. The hypoxia-induced phenotype is the predominant form of differentiation in stroma-poor tumors, while in stroma-rich tumors the chromaffin phenotype coexists with ganglion cell-like differentiation. The findings provide new insights into the biological diversity which is a striking feature of this group of tumors.

  18. Development of Neuroendocrine Prostate Cancers by the Ser/Arg Repetitive Matrix 4-Mediated RNA Splicing Network

    Directory of Open Access Journals (Sweden)

    Ahn R. Lee

    2018-04-01

    Full Text Available While the use of next-generation androgen receptor pathway inhibition (ARPI therapy has significantly increased the survival of patients with metastatic prostate adenocarcinoma (AdPC, several groups have reported a treatment-resistant mechanism, whereby cancer cells can become androgen receptor (AR indifferent and gain a neuroendocrine (NE-like phenotype. This subtype of castration-resistant prostate cancer has been termed “treatment-induced castration-resistant neuroendocrine prostate cancer” (CRPC-NE. Recent reports indicate that the overall genomic landscapes of castration-resistant tumors with AdPC phenotypes and CRPC-NE are not significantly altered. However, CRPC-NE tumors have been found to contain a NE-specific pattern throughout their epigenome and splicing transcriptome, which are significantly modified. The molecular mechanisms by which CRPC-NE develops remain unclear, but several factors have been implicated in the progression of the disease. Recently, Ser/Arg repetitive matrix 4 (SRRM4, a neuronal-specific RNA splicing factor that is upregulated in CRPC-NE tumors, has been shown to establish a CRPC-NE-unique splicing transcriptome, to induce a NE-like morphology in AdPC cells, and, most importantly, to transform AdPC cells into CRPC-NE xenografts under ARPI. Moreover, the SRRM4-targeted splicing genes are highly enriched in various neuronal processes, suggesting their roles in facilitating a CRPC-NE program. This article will address the importance of SRRM4-mediated alternative RNA splicing in reprogramming translated proteins to facilitate NE differentiation, survival, and proliferation of cells to establish CRPC-NE tumors. In addition, we will discuss the potential roles of SRRM4 in conjunction with other known pathways and factors important for CRPC-NE development, such as the AR pathway, TP53 and RB1 genes, the FOXA family of proteins, and environmental factors. This study aims to explore the multifaceted functions of SRRM4

  19. Mechanical stress induces neuroendocrine and immune responses of sea cucumber ( Apostichopus japonicus)

    Science.gov (United States)

    Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin

    2015-04-01

    Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.

  20. Forebrain pathways and their behavioural interactions with neuroendocrine and cardiovascular function in the rat

    NARCIS (Netherlands)

    Bohus, B; Koolhaas, JM; Korte, SM; Roozendaal, B; Wiersma, A

    1. The forebrain is a major organizer of the complex behavioural, physiological and neuroendocrine responses to environmental challenges of a stressful nature. 2. Combined physiological and neuroanatomical studies suggest that a specific forebrain-brain stem network, composed of connections between

  1. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Loft, Annika

    2010-01-01

    PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. EXPERIMENTAL DESIGN: Ninety...

  2. Carcinoid Syndrome and Carcinoid Heart Disease as Manifestations of Non-Metastatic Ovarian Neuroendocrine Tumour

    Directory of Open Access Journals (Sweden)

    Joana Simões-Pereira

    2017-05-01

    Full Text Available The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

  3. Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Knigge, Ulrich

    2015-01-01

    Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when...

  4. Neuroendocrine-immune interaction: regulation of inflammation via G-protein coupled receptors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Aa, van der L.M.; Chadzinska, M.K.

    2013-01-01

    Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines,

  5. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

  6. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  7. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  8. Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours

    DEFF Research Database (Denmark)

    Janson, Eva Tiensuu; Sørbye, Halfdan; Welin, Staffan

    2010-01-01

    The diagnostic work-up and treatment of patients with neuroendocrine tumours has undergone a major change during the last decade. New diagnostic possibilities and treatment options have been developed. These Nordic guidelines, written by a group with a major interest in the subject, summarises ou...

  9. Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience.

    Science.gov (United States)

    Ito, Hiromichi; Abramson, Michael; Ito, Kaori; Swanson, Edward; Cho, Nancy; Ruan, Daniel T; Swanson, Richard S; Whang, Edward E

    2010-05-01

    The aims of this study were to evaluate contemporary outcomes associated with the surgical management of pancreatic neuroendocrine tumors (PNETs) and to assess the prognostic value of the World Health Organization (WHO) classification and TNM staging for PNETs. The medical records of 73 consecutive patients with PNETs treated at a single institution from January 1992 through September 2006 were reviewed. Survival was analyzed with the Kaplan-Meier method (median follow-up: 43 months). Median patient age was 52 years (range, 19-83 years), and 36 (49%) patients were male. Thirty-three patients had a well-differentiated neuroendocrine tumor (WDT), 26 had a well-differentiated neuroendocrine carcinoma (WDCa), and 14 had a poorly differentiated neuroendocrine carcinoma (PDCa). Fifty (68%) patients underwent potentially curative resection, and the 5-year disease-specific survival (DSS) rate for the entire cohort was 62%. WHO classification and TNM staging system provided good prognostic stratification of patients; 5-year DSS rates were 100% for WDT, 57% for WDCa, 8% for PDCa, respectively, by WHO classification (p < 0.001), and 100% for stage 1, 90% for stage 2, 57% for stage 3, and 8% for stage 4, respectively, by TNM stage (p < 0.001). Among the patients who underwent potentially curative resection, nodal status, distant metastasis, and tumor grade were significant prognostic factors. WHO classification and TNM staging are useful for prognostic stratification among patients with PNETs.

  10. Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

    Directory of Open Access Journals (Sweden)

    Caroline I. E. Renner

    2015-09-01

    Full Text Available Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed.

  11. Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature

    NARCIS (Netherlands)

    Rosmalen, M.H. Van; Reijnen, C.; Boll, D.; Pijnenborg, J.M.A.; Wurff, A.A. van der; Piek, J.M.

    2016-01-01

    BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the

  12. Effects of repetitive hypoglycemia on neuroendocrine response and brain tyrosine hydroxylase activity in the rat.

    NARCIS (Netherlands)

    Figlewicz, D. P.; Van Dijk, G.; Wilkinson, C. W.; Gronbeck, P.; Higgins, M.; Zavosh, A.

    2002-01-01

    Hypoglycemia-associated autonomic failure (HAAF) is a syndrome of acute adaptation to a metabolic stressor, in which neuroendocrine responses to repetitive hypoglycemic bouts are blunted. The CNS mechanisms that contribute to HAAF are unknown. In the present study, we modeled HAAF in the rat and

  13. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Science.gov (United States)

    Endocrine and neuroendocrine neoplasias may be inherited in syndromes such as multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), familial pheochromocytoma and paraganglioma, and Carney-Stratakis syndrome. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

  14. Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

    NARCIS (Netherlands)

    Heikens, J.; Michiels, E. M.; Behrendt, H.; Endert, E.; Bakker, P. J.; Fliers, E.

    1998-01-01

    The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25

  15. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  16. The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity

    NARCIS (Netherlands)

    Meerlo, P; Horvath, KM; Nagy, GM; Bohus, B; Koolhaas, JM

    1999-01-01

    Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress

  17. Neuroendocrine tumour of the cervix: A case report and review of ...

    African Journals Online (AJOL)

    Cervical neuroendocrine tumours are rare accounting for only 2% of cervical cancers. They pose a management challenge. We present a case of a 26-year old who presented with bleeding pervaginum three months post partum and a cervical mass on speculum examinations. Further examination and histology revealed an ...

  18. Neuroendocrine and cardiovascular reactions to acute psychological stress are attenuated in smokers

    NARCIS (Netherlands)

    Ginty, Annie T; Jones, Alexander; Carroll, Douglas; Roseboom, Tessa J; Phillips, Anna C; Painter, Rebecca; de Rooij, Susanne R

    2014-01-01

    A number of studies have now examined the association between smoking and the magnitude of physiological reactions to acute psychological stress. However, no large-scale study has demonstrated this association incorporating neuroendocrine in addition to cardiovascular reactions to stress. The

  19. Polyunsaturated fatty acid consumption, plasma cholesterol concentration and neuroendocrine response to mental and physical task load

    NARCIS (Netherlands)

    Odink, J.; Kramer, F.M.; Beek, E.J. van der; Thissen, J.T.N.M.; Kempen, H.J.M.; Berg, H. van den; Egger, R.J.; Wientjes, C.J.E.

    1989-01-01

    This study was designed to investigate the relation between fatty acid consumption, total plama cholesterol and neuroendocrine response to exposure to stress, factors thought to play a role in the development of coronary heart disease. For this purpose 32 apparently healthy male volunteers were

  20. Long-term survival after surgical management of neuroendocrine hepatic metastases

    Science.gov (United States)

    Glazer, Evan S; Tseng, Jennifer F; Al-Refaie, Waddah; Solorzano, Carmen C; Liu, Ping; Willborn, Katherine A; Abdalla, Eddie K; Vauthey, Jean-Nicolas; Curley, Steven A

    2010-01-01

    Background: Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases. Methods: Patients (n= 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival. Results: The median age was 56.8 years (range 11.5–80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3–56.8, P= 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P∼ 0.8). Discussion: Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival. PMID:20662794

  1. Neuroendocrine tumor of the appendix inside an incarcerated Amyand’s hernia

    Directory of Open Access Journals (Sweden)

    Khaled Y. Elbanna

    2015-01-01

    An incidental finding of neuroendocrine tumor of the appendix in a patient with s hernia is extremely rare. A high index of suspicion is the key to diagnose such a coincidence in order to safely and optimally treat such a condition.

  2. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  3. Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors.

    Science.gov (United States)

    Sepúlveda-Méndez, Jesús; de Murphy, Consuelo Arteaga; Pedraza-López, Martha; Murphy-Stack, Eduardo; Rojas-Bautista, Juan Carlos; González-Treviño, Ofelia

    2012-01-01

    Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases. Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with ⁹⁹mTc-TOC. The patients were injected with 500-600 MBq ⁹⁹mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the ⁹⁹mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. The validity of ⁹⁹mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76

  4. Computed tomography characterization of neuroendocrine tumors of the thymus can aid identification and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Wang, De-ling; Liu, Xue-wen; Geng, Zhi-jun; Xie, Chuan-miao [State Key Lab. of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen Univ., Guangzhou (China)], e-mail: xchuanm@sysucc.org.cn

    2013-03-15

    Background: Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. The few studies reporting these tumors have focused on the clinical manifestations and do not provide a summary of characteristic computed tomography (CT) findings. Purpose: To investigate the CT appearances of neuroendocrine tumors of the thymus in order to improve the diagnostic and resection efficacy. Material and Methods: Nine cases of pathologically identified thymic neuroendocrine tumors were retrospectively analyzed by CT. All the patients underwent non-enhanced and contrast-enhanced CT. Multiple CT features were examined, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. Results: A total of nine masses were examined in this study. The maximum tumor diameter ranged from 5 to 14 cm (average, 9 cm). The shapes of six masses were lobulated and three were rounded or oval and the margins of seven masses were unclear while two masses were sharp. All the masses showed hypo density or isodensity compared to muscles in the anterior thoracic wall on non-enhanced CT images. Two masses showed homogeneous attenuation by non-enhanced CT imaging and moderate homogeneous enhancement after contrast administration, while seven masses showed heterogeneous attenuation with patchy low-attenuation foci and showed moderate to strong heterogeneous enhancement. Involvement of adjacent structures was observed in six cases. Five cases were observed to have lymph node metastases and four cases had distant metastases. Conclusion: Neuroendocrine tumors of the thymus are rare tumors of the anterior mediastinum with a number of distinct CT characteristics. Most importantly, the density of the tumors was heterogeneous with necrosis or cystic degeneration and moderately or strongly enhancement after bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis

  5. Peptide receptor radionuclide therapy as neoadjuvant therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Partelli, Stefano; Bertani, Emilio; Bartolomei, Mirco; Perali, Carolina; Muffatti, Francesca; Grana, Chiara Maria; Schiavo Lena, Marco; Doglioni, Claudio; Crippa, Stefano; Fazio, Nicola; Zamboni, Giuseppe; Falconi, Massimo

    2018-04-01

    Peptide receptor radionuclide therapy is a valid therapeutic option for pancreatic neuroendocrine neoplasms. The aim of this study was to describe an initial experience with the use of peptide receptor radionuclide therapy as a neoadjuvant agent for resectable or potentially resectable pancreatic neuroendocrine neoplasms. The postoperative outcomes of 23 patients with resectable or potentially resectable pancreatic neuroendocrine neoplasms at high risk of recurrence who underwent neoadjuvant peptide receptor radionuclide therapy (peptide receptor radionuclide therapy group) were compared with 23 patients who underwent upfront surgical operation (upfront surgery group). Patients were matched for tumor size, grade, and stage. Median follow-up was 61 months. The size (median greatest width) of the primary pancreatic neuroendocrine neoplasms decreased after neoadjuvant peptide receptor radionuclide therapy (59 to 50 mm; P=.047). There were no differences in intraoperative and postoperative outcomes and there were no operative deaths, but the risk of developing a pancreatic fistula tended to be less in the peptide receptor radionuclide therapy group when compared to the upfront surgery group (0/23 vs 4/23; P radionuclide therapy group (n= 9/23 vs 17/23; P.2) differed between groups, but progression-free survival in the 31 patients who had an R0 resection seemed to be greater in the 15 patients in the peptide receptor radionuclide therapy group versus 16 patients the upfront group (median progression-free survival not reached vs 36 months; Pradionuclide therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms in patients with high-risk features of recurrence seems to be beneficial, but well-designed and much larger prospective trials are needed to confirm the safety and the oncologic value of this approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment

    NARCIS (Netherlands)

    De Proost, Ian; Pintelon, Isabel; Brouns, Inge; Kroese, A; Riccardi, Daniela; Kemp, Paul J.; Timmermans, Jean-Pierre; Adriaensen, Dirk

    Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of neuroendocrine cells invariably accompanied by Clara-like cells. Together with NEBs, Clara-like cells form the so-called "NEB microenvironment," which recently has been assigned a potential pulmonary stem cell niche. Conclusive

  7. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II-specific NE tumour types

    DEFF Research Database (Denmark)

    Oberg, Kjell; Astrup, Lone Bording; Eriksson, Barbro

    2004-01-01

    Part II of the guidelines contains a description of epidemiology, histopathology, clinical presentation, diagnostic procedure, treatment, and survival for each type of neuroendocrine tumour. We are not only including gastroenteropancreatic tumours but also bronchopulmonary and thymic neuroendocri...

  8. Diagnosis and Treatment of Gastroenteropancreatic Neuroendocrine Tumors: Current Data on a Prospectively Collected, Retrospectively Analyzed Clinical Multicenter Investigation

    OpenAIRE

    Niederle, Martin B.; Niederle, Bruno

    2011-01-01

    Clinical information concerning diagnosis, symptoms, and treatment of 277 patients with gastrointestinal neuroendocrine tumors (including pancreatic tumors) diagnosed prospectively within 1 year were analyzed. Endoscopic and surgical techniques are the key to both correct diagnosis and effective treatment.

  9. Neuroendocrine recovery after 2-week 12-h day and night shifts: an 11-day follow-up

    NARCIS (Netherlands)

    Merkus, S.L.; Holte, K.A.; Huysmans, M.A.; Hansen, A.M.; van de Ven, P.M.; van Mechelen, W.; van der Beek, A.J.

    2015-01-01

    Purpose: The study aimed to investigate the course and duration of neuroendocrine recovery after 2-week 12-h day and night shift working periods and to study whether there were differences in recovery between the shift groups.

  10. A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel E. Beard

    2017-01-01

    Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

  11. Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung......, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features....

  12. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    Science.gov (United States)

    2017-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  13. Stem cells in psoriasis.

    Science.gov (United States)

    Hou, Ruixia; Li, Junqin; Niu, Xuping; Liu, Ruifeng; Chang, Wenjuan; Zhao, Xincheng; Wang, Qiang; Li, Xinhua; Yin, Guohua; Zhang, Kaiming

    2017-06-01

    Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently. Copyright © 2016. Published by Elsevier B.V.

  14. Cystic pancreatic neuroendocrine tumors (cPNETs: a systematic review and meta-analysis of case series

    Directory of Open Access Journals (Sweden)

    Luis Hurtado-Pardo

    Full Text Available Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387 were sporadic tumors and 10.3% (n = 40 corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135. Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338, and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb, and 12.2% were advanced (III-IV. Disease-free survival at 5 years in stages (I-IIIa and (IIIb-IV was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001 in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5% and multifocal (28.1% tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

  15. 99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

    Science.gov (United States)

    Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

    2015-05-01

    The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

  16. {sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

    2013-06-15

    6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

  17. Linking extremely low birth weight and internalizing behaviors in adult survivors: Influences of neuroendocrine dysregulation.

    Science.gov (United States)

    Waxman, Jordana A; Lieshout, Ryan J Van; Boyle, Michael H; Saigal, Saroj; Schmidt, Louis A

    2015-05-01

    Young adult survivors of extremely low birth weight (ELBW; neuroendocrine functioning on the link between being born at ELBW and internalizing behaviors at age 30-35. Salivary cortisol was collected 20 min after completion of a social stress task in 83 ELBW adult survivors and 89 normal birth weight (NBW; >2500 g) controls. Using a median split, participants were separated into two groups (high or low afternoon cortisol levels). ELBW survivors with "high" afternoon cortisol levels self-reported significantly higher levels of internalizing behaviors compared to those with "low" afternoon cortisol levels. This association between afternoon cortisol and internalizing symptoms did not exist among NBW controls. These results are suggestive of a differential susceptibility for internalizing behaviors among ELBW survivors, depending on their ability to regulate neuroendocrine responses. © 2015 Wiley Periodicals, Inc.

  18. Extensive multiarterial resection attending total duodenopancreatectomy and adrenalectomy for MEN-1-associated neuroendocrine carcinomas.

    Science.gov (United States)

    Egorov, Vyacheslav Ivanovich; Kharazov, Alexander Felixovich; Pavlovskaya, Alla Ivanovna; Petrov, Roman Valeryevich; Starostina, Natalia Sergeevna; Kondratiev, Eugeny Valerievich; Filippova, Ekaterina Mikhailovna

    2012-10-27

    Pancreatic neuroendocrine tumors (PNTs) are relatively uncommon although these neoplasms have been noted to grow in occurrence in recent decades. Surgical removal of locally advanced PNTs involving major vessels and adjacent organs is warranted by reason of an appreciably more favorable prognosis as compared to exocrine pancreas cancer. We are reporting a case of successful multi-organ resection combined with a wide excision of the superior mesenteric, common, proper, left and right hepatic arteries (in the presence of the hepatomesenteric trunk variant of aberrant arterial anatomy) for multifocal PNTs in the setting of multiple neuroendocrine neoplasia type 1 syndrome. The procedure resulted in pain abolition, a significant improvement in the patient's life quality and allowed her to return to work. Follow-up computed tomography at 15 mo post-surgery showed no evidence of disease recurrence.

  19. Imaging findings of neuroendocrine neoplasm in biliary duct with liver metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Hwa; Chung, Dong Jin; Hahn, Sung Tae; Lee, Jae Moon [Dept. of Radiology, Yeouido St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2013-09-15

    A 64-year-old man was transferred to our hospital because of indigestion and jaundice. The initial abdominal CT and MRI revealed a 2.0 cm enhancing mass in the proximal common bile duct (CBD) with several enlarged lymph nodes. The mass was presumed to be a cholangiocarcinoma, and a CBD segmental resection and choledochojejunostomy was performed. However, the final diagnosis was that of a mixed endocrine-exocrine carcinoma, a high-grade neuroendocrine neoplasm. Seven months after the operation, a follow-up abdominal CT study revealed multiple small arterial enhancing nodules in both hepatic lobes. A sono-guided liver biopsy confirmed these as metastastic mixed endocrine-exocrine carcinoma. This case is unique in that the imaging study regarding the neuroendocrine neoplasm of biliary duct has not been previously reported.

  20. Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Holstein-Rathlou, N H

    2001-01-01

    To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits...... sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P Renal free water clearance increased during WI in control subjects but not in HF......, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast...

  1. An Eustachian Tube Neuroendocrine Carcinoma: A Previously Undescribed Entity and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gavin J. le Nobel

    2016-01-01

    Full Text Available Primary sinonasal and middle ear neuroendocrine carcinomas are rare malignancies of the head and neck. Owing to the rarity of these tumors, the clinical behavior and optimal management of these tumors are not well defined. We present a case of an incidentally discovered sinonasal neuroendocrine carcinoma that was found to originate from the Eustachian tube, which has not previously been described in the literature. This patient was treated with primary surgical resection using a combination of transnasal and transaural approaches and achieved an incomplete resection. Follow-up imaging demonstrated continued tumor growth in the Eustachian tube as well as a new growth in the ipsilateral cerebellopontine angle and findings suspicious of perineural invasion. However, the tumor exhibited a benign growth pattern and despite continued growth the patient did not receive additional treatment and he remains asymptomatic 35 months following his original surgery.

  2. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

    Science.gov (United States)

    Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

    2011-01-01

    Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

  3. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...... patients were evaluable for response: Five achieved stable disease (SD) and 17 progressed (PD). The median overall survival for the 22 patients was 3.2 months and the median progression-free survival was 2.1 months. The one-year survival was 18%. There were no treatment related deaths. The treatment...

  4. Neuroendocrine control in social relationships in non-human primates: Field based evidence.

    Science.gov (United States)

    Ziegler, Toni E; Crockford, Catherine

    2017-05-01

    Primates maintain a variety of social relationships and these can have fitness consequences. Research has established that different types of social relationships are unpinned by different or interacting hormonal systems, for example, the neuropeptide oxytocin influences social bonding, the steroid hormone testosterone influences dominance relationships, and paternal care is characterized by high oxytocin and low testosterone. Although the oxytocinergic system influences social bonding, it can support different types of social bonds in different species, whether pair bonds, parent-offspring bonds or friendships. It seems that selection processes shape social and mating systems and their interactions with neuroendocrine pathways. Within species, there are individual differences in the development of the neuroendocrine system: the social environment individuals are exposed to during ontogeny alters their neuroendocrine and socio-cognitive development, and later, their social interactions as adults. Within individuals, neuroendocrine systems can also have short-term effects, impacting on social interactions, such as those during hunting, intergroup encounters or food sharing, or the likelihood of cooperating, winning or losing. To understand these highly dynamic processes, extending research beyond animals in laboratory settings to wild animals living within their natural social and ecological setting may bring insights that are otherwise unreachable. Field endocrinology with neuropeptides is still emerging. We review the current status of this research, informed by laboratory studies, and identify questions particularly suited to future field studies. We focus on primate social relationships, specifically social bonds (mother-offspring, father-offspring, cooperative breeders, pair bonds and adult platonic friendships), dominance, cooperation and in-group/out-group relationships, and examine evidence with respect to the 'tend and defend' hypothesis. Copyright © 2017

  5. Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Singh S

    2014-08-01

    Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

  6. Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases

    OpenAIRE

    Wang, Wei; Seeruttun, Sharvesh Raj; Fang, Cheng; Zhou, Zhiwei

    2014-01-01

    A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography (PET)/computed tomography (CT) demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor ...

  7. Paradigm shift in theranostics of neuroendocrine tumors: conceptual horizons of nanotechnology in nuclear medicine.

    Science.gov (United States)

    Arora, Geetanjali; Bandopadhyaya, Gurupad

    2018-04-01

    We present a comprehensive review of Neuroendocrine Tumors (NET) and the current and developing imaging and therapeutic modalities for NET with emphasis on Nuclear Medicine modalities. Subsequently, nanotechnology and its emerging role in cancer management, especially NET, are discussed. The article is both educative and informative. The objective is to provide an insight into the developments made in nuclear medicine and nanotechnology towards management of NET, individually as well as combined together.

  8. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles

    OpenAIRE

    Grippo, Angela J.; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C. Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks o...

  9. Induction of neuroendocrine transdifferentiation by androgen ablation is associated with expression of markers of senescence

    Czech Academy of Sciences Publication Activity Database

    Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel

    2009-01-01

    Roč. 276, č. 1 (2009), s. 246-247 ISSN 1742-464X. [34th FEBS Congress. 04.07.2009-09.07.2009, Prague] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine transdifferentiation * cyclin D1 * senescence associated beta-galactosidase Subject RIV: BO - Biophysics

  10. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    National Research Council Canada - National Science Library

    Evans, Christopher P

    2006-01-01

    ... enhancer region, which is primarily stimulated by androgens. We have shown that gastrin-releasing peptide prostate cancer cells have their growth in soft agar inhibited by the specific Src inhibitor AZD0530...

  11. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    Science.gov (United States)

    2008-09-01

    Short-Term Therapy with Bacillus Calmette-Guerin (BCG) in Patients with Non-Muscle-Invasive Bladder Cancer. Eur Urol. epub. 10. 2007 Cambio A.J...Leonhardt M, Janssen M, Konrad L, Bjartell A, Abrahamsson PA. Neurogenic origin of human prostate endocrine cells. Urology 1999; 53: 1041–1048. 13 Luttrell...membrane (Corning, Inc.). A549 cells were then infected with a mix of DMEM, virus-containing supernatant (1:1), and polybrene (4 Ag/mL). After

  12. Neuroendocrine mechanisms underlying behavioral stability: implications for the evolutionary origin of personality.

    Science.gov (United States)

    Duckworth, Renée A

    2015-12-01

    Personality traits are behaviors that show limited flexibility over time and across contexts, and thus understanding their origin requires an understanding of what limits behavioral flexibility. Here, I suggest that insight into the evolutionary origin of personality traits requires determining the relative importance of selection and constraint in producing limits to behavioral flexibility. Natural selection as the primary cause of limits to behavioral flexibility assumes that the default state of behavior is one of high flexibility and predicts that personality variation arises through evolution of buffering mechanisms to stabilize behavioral expression, whereas the constraint hypothesis assumes that the default state is one of limited flexibility and predicts that the neuroendocrine components that underlie personality variation are those most constrained in flexibility. Using recent work on the neurobiology of sensitive periods and maternal programming of offspring behavior, I show that some of the most stable aspects of the neuroendocrine system are structural components and maternally induced epigenetic effects. Evidence of numerous constraints to changes in structural features of the neuroendocrine system and far fewer constraints to flexibility of epigenetic systems suggests that structural constraints play a primary role in the origin of behavioral stability and that epigenetic programming may be more important in generating adaptive variation among individuals. © 2015 New York Academy of Sciences.

  13. The role of the neuroendocrine and immune systems in the pathogenesis of depression.

    Science.gov (United States)

    Ogłodek, Ewa; Szota, Anna; Just, Marek; Moś, Danuta; Araszkiewicz, Aleksander

    2014-10-01

    Development of depression is associated with the body's response to prolonged stress, which adversely affects the functioning of the nervous, endocrine and immune systems. Prolonged stress can lead to the development of a so-called allostatic load and reduction of concentration of brain-derived neurotrophic factor. These changes result in impairment of neurogenesis and synaptic remodeling process. This article illustrates the involvement of key mediators of allostasis such as the neuroendocrine and immune systems, in the pathogenesis of depression. The literature concerning the contribution of the neuroendocrine and immune systems to depression incidence was reviewed. Development of depression is associated with disturbance of the body's allostasis and inflammatory activation of the immune system. It leads to a chronic increase in the concentration of cortisol and proinflammatory cytokines, which results in an allostatic load. This load leads to neurodegeneration, eventually causing irreversible cognitive impairment and permanent disability. Determination of the concentration of chemokines and their receptors is an important indicator of activation of the immune and neuroendocrine systems. The activity of these systems reflects the severity of the disease and provides important information for effective antidepressant treatment. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Classification of gastro-entero-pancreatic neuroendocrine tumors; Klassifikation gastroenteropankreatischer neuroendokriner Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Perren, A. [Klinikum Rechts der Isar, Technische UniversitaetMuenchen, Institut fuer Pathologie und pathologische Anatomie, Muenchen (Germany); Schmitt, A. [Universitaetsspital Zuerich, Institut fuer Klinische Pathologie, Departement Pathologie, Zuerich (Switzerland); Komminoth, P. [Stadtspital Triemli, Zuerich (Switzerland). Institut fuer Pathologie; Pavel, M. [Charite, Universitaetsmedizin Berlin (Germany). Medizinische Klinik mit Schwerpunkt Hepatologie and Gastroenterologie

    2009-03-15

    Tumors of the disseminated/diffuse neuroendocrine system (NET) are characterized by a common phenotype. However, the biology varies according to histomorphology, endocrine symptoms and organ of origin. The WHO classification takes these differences into account and uses a common framework, where the parameters size and extent of invasion vary according to the organ of origin. In order to achieve a further standardization of reporting the European Neuroendocrine Tumor Society (ENETS) recently proposed a tumor-node-metastasis (TNM) staging and grading system for gastro-entero-pancreatic NET. (orig.) [German] Tumoren des disseminierten/diffusen neuroendokrinen Systems sind durch einen gemeinsamen Phaenotyp gekennzeichnet. In ihrer Biologie unterscheiden sich neuroendokrine Tumoren (NET) jedoch bzgl. Morphologie, endokrinologischer Symptomatik und Ursprungsorgan. Die WHO-Klassifikation traegt diesen Unterschieden Rechnung und klassifiziert NET nach einem einheitlichen Vorgehen, wobei die Parameter Groesse und Invasionstiefe je nach Ursprungsorgan variieren. Um die Nomenklatur weiter zu vereinheitlichen, wurde vor kurzem von der ''European Neuroendocrine Tumor Society'' (ENETS) der Vorschlag einer TNM-Stadien-Einteilung und Graduierung gastroenteropankreatischer NET vorgelegt. (orig.)

  15. Relaxin-3/RXFP3 signaling and neuroendocrine function – A perspective on extrinsic hypothalamic control

    Directory of Open Access Journals (Sweden)

    Despina E Ganella

    2013-09-01

    Full Text Available Complex neural circuits within the hypothalamus that govern essential autonomic processes and associated behaviors signal using amino acid and monoamine transmitters and a variety of neuropeptide (hormone modulators, often via G-protein coupled receptors (GPCRs and associated cellular pathways. Relaxin-3 is a recently identified neuropeptide that is highly conserved throughout evolution. Neurons expressing relaxin-3 are located in the brainstem, but broadly innervate the entire limbic system including the hypothalamus. Extensive anatomical data in rodents and non-human primate, and recent regulatory and functional data, suggest relaxin-3 signaling via its cognate GPCR, RXFP3, has a broad range of effects on neuroendocrine function associated with stress responses, feeding and metabolism, motivation and reward, and possibly sexual behavior and reproduction. Therefore, this article aims to highlight the growing appreciation of the relaxin-3/RXFP3 system as an important ‘extrinsic’ regulator of the neuroendocrine axis by reviewing its neuroanatomy and its putative roles in arousal-, stress- and feeding-related behaviors and links to associated neural substrates and signaling networks. Current evidence identifies RXFP3 as a potential therapeutic target for treatment of neuroendocrine disorders and related behavioral dysfunction.

  16. Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos.

    Science.gov (United States)

    Venerosi, A; Ricceri, L; Tait, S; Calamandrei, G

    2012-12-01

    The complexity of the neuroendocrine level of investigation requires the assessment of behavioral patterns that extend beyond the reproductive functions, which are age- and sex-specific in rodents, described by defined clusters of behavioral items regulated by genetic, hormonal, and epigenetic factors. The study of social behavior in laboratory rodents reveals sex-dimorphic effects of environmental chemicals that may be undetected either by a traditional neurotoxicological approach or referring to the classical definition of endocrine disrupting chemicals. Here we review data on the neurobehavioral effects of developmental exposure to the non-persistent organophosphorus insecticide chlorpyrifos, whose neurotoxic activity at low doses is currently a matter of concern for children's health. In mice exposed to chlorpyrifos in utero and/or in early development social/emotional responses are differently affected in the two sexes in parallel with sex-dependent interference on hypothalamic neuroendocrine pathways regulating social behaviors (vasopressin, oxytocin, and steroid regulated systems). Through the analysis of complex sex-dimorphic behavioral patterns we show that neurotoxic and endocrine disrupting activities of CPF overlap. This widely diffused organophosphorus pesticide might thus be considered as a neuroendocrine disruptor possibly representing a risk factor for sex-biased neurodevelopmental disorders in children. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Hotspot detection in pancreatic neuroendocrine tumors: density approximation by α-shape maps

    Science.gov (United States)

    Niazi, M. K. K.; Hartman, Douglas J.; Pantanowitz, Liron; Gurcan, Metin N.

    2016-03-01

    The grading of neuroendocrine tumors of the digestive system is dependent on accurate and reproducible assessment of the proliferation with the tumor, either by counting mitotic figures or counting Ki-67 positive nuclei. At the moment, most pathologists manually identify the hotspots, a practice which is tedious and irreproducible. To better help pathologists, we present an automatic method to detect all potential hotspots in neuroendocrine tumors of the digestive system. The method starts by segmenting Ki-67 positive nuclei by entropy based thresholding, followed by detection of centroids for all Ki-67 positive nuclei. Based on geodesic distance, approximated by the nuclei centroids, we compute two maps: an amoeba map and a weighted amoeba map. These maps are later combined to generate the heat map, the segmentation of which results in the hotspots. The method was trained on three and tested on nine whole slide images of neuroendocrine tumors. When evaluated by two expert pathologists, the method reached an accuracy of 92.6%. The current method does not discriminate between tumor, stromal and inflammatory nuclei. The results show that α-shape maps may represent how hotspots are perceived.

  18. Dimethyl-Benz(aanthracene: A mammary carcinogen and a neuroendocrine disruptor

    Directory of Open Access Journals (Sweden)

    Bernard Kerdelhué

    2016-12-01

    Full Text Available Polycyclic Aromatic Hydrocarbons (PAHs are potent carcinogens. Among these, dimethylbenz(aanthracene (DMBA is well known for its capacity to induce mammary carcinomas in female Sprague-Dawley (SD rats. Ovariectomy suppresses the susceptibility of this model to DMBA, thus suggesting that the inducible action of the carcinogen depends on ovarian hormones. The promotion of DMBA-induced adenocarcinoma is accompanied by a series of neuroendocrine disruptions of both Hypothalamo-Pituitary-Gonadal (HPG and Hypothalamo-Pituitary-Adrenal (HPA axes and of the secretion of melatonin during the latency period of 2 months that precedes the occurrence of the first mammary tumor. The present review analyses the various neuroendocrine disruptions that occur along the HPG and the HPA axes, and the marked inhibitory effect of the carcinogen on melatonin secretion. The possible relationships between the neuroendocrine disruptions, which essentially consist in an increased pre-ovulatory secretion of 17β-estradiol and prolactin, associated with a marked reduction of melatonin secretion, and the decrease in gene expression of the receptors for aryl-hydrocarbons receptor (AhR and 17β-estradiol (ERα; ERβ are also discussed.

  19. The clinical value of scintigraphy of neuroendocrine tumors using (99m)Tc-HYNIC-TOC.

    Science.gov (United States)

    Artiko, V; Sobic-Saranovic, D; Pavlovic, S; Petrovic, M; Zuvela, M; Antic, A; Matic, S; Odalovic, S; Petrovic, N; Milovanovic, A; Obradovic, V

    2012-01-01

    To assess the value of whole body scintigraphy using (99m)Tc-HYNIC-TOC (Tektrotyd) and with single photon emission computerized tomography (SPECT) in the detection of primary and metastatic neuroendocrine tumors (NETs). Thirty patients with different neuroendocrine tumors, mainly gastroenteropancreatic (GEP), were investigated. Whole body scintigraphy was performed 2 h (if necessary 10 min and 24h) after i.v. administration of 740 Mbq (99m)Tc-Tektrotyd, Polatom. In cases of unclear findings obtained by whole body scintigraphy, investigation was followed by SPECT. From 12 patients with NETs of unknown origin, there were 10 true positive (TP), and 2 false negative (FN) findings. Diagnosis was made with SPECT in 6 patients. From 8 patients with gut carcinoids, there were 4 TP, 2 true negative (TN), one FN, and one false positive (FP) finding. Diagnosis was made with SPECT in 2 patients. From 7 patients with neuroendocrine pancreatic carcinomas there were 4 TP and 3 TN findings. Diagnosis was made with SPECT in 2 patients. From 3 patients with gastrinomas there were 2 TP findings and one TN findings. Diagnosis was made with SPECT findings in 2 patients. Sensitivity of (99m)Tc-HYNIC-TOC was 87%, specificity 86%, positive predictive value 95%, negative predictive value 67% and accuracy 87%. We concluded that scintigraphy with (99m)Tc-Tektrotyd is an useful method for diagnosis, staging and follow up of the patients with NETs.

  20. Solitary hypervascular liver metastasis from neuroendocrine tumor mimicking hepatocellular cancer: All that glitters is not gold

    International Nuclear Information System (INIS)

    Laroia, Shalini Thapar; Sasturkar, Shridhar; Rastogi, Archana; Pamecha, Viniyendra

    2015-01-01

    Neuroendocrine tumor metastases to the liver can mimic primary hepatocellular carcinoma (HCC) on imaging, cytology, and core biopsy. We present a case study along with the literature review of a patient who presented as a solitary liver mass mimicking HCC and subsequently underwent a partial hepatectomy. The histopathology and immunohistochemisrty of the resected specimen revealed metastatic neuroendocrine carcinoma. Positron emission tomography (PET) scan with 68 Ga-DOTA-NaI-octreotide ( 68 Ga-DOTANOC) localized the primary tumor in the ileum. A curative follow-up surgery for resection of the small bowel containing the primary tumor was carried out. This case illustrates the shortcomings of routine imaging methods, utility of immunocytochemistry and the importance of 68 Ga-DOTANOC PET in determining the metastatic spread as well as the origin of neuroendocrine tumors (NETs). This case report attempts to highlight the current imaging paradigms and management strategy of midgut and other NET's at the point of detection, staging and follow-up