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Sample records for alters neuroendocrine markers

  1. An Overview of Neuroendocrine Tumour Markers

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    Ersin Özaslan

    2014-12-01

    Full Text Available As there are many different subtypes of neuroendocrine tumors (NETs, many kinds of markers are used for their diagnosis and follow-up. Most of these markers, such as calcitonin, catecholamines, 5-hydroxyindoleacetic acid (5-HIAA, insulin, gastrin, pancreatic polypeptide, and glucagon are specific to one subtype of NET. In addition, there are also general markers used in various NET subtypes; the most commonly used ones are chromogranin-A (CgA, neuron-specific enolase (NSE, and synaptophysin. The sensitivity and specificity levels of CgA are highest among all NET markers. However, specific markers, such as calcitonin in medullary thyroid carcinoma, insulin in insulinoma and cathecolamines in feocromocitoma are more useful than CgA. CgA is an auxiliary marker in cases with relapse or metastasis of such functional NETs. Carcinoid syndrome is characterized by serotonin hypersecretion with the other products and 5-HIAA level is used to determine the serotonin hypersecretion. Thus, 5-HIAA is the specific marker for carcinoid tumors which comprise two-thirds of all NETs.

  2. Neuroendocrine alterations in the exercising human: implications for energy homeostasis.

    Science.gov (United States)

    Fuqua, John S; Rogol, Alan D

    2013-07-01

    Complex mechanisms exist in the human to defend against adverse effects of negative energy balance. These include alterations of hormone secretion affecting the growth hormone/insulin-like growth factor system, the adrenal axis, and the reproductive system, particularly in females. Energy deficits are least partially offset by neuroendocrine mechanisms regulating appetite and satiety. The complex feedback mechanisms reporting peripheral fat and energy stores to the central nervous system involve secretion of the peptide hormones leptin and ghrelin, which act centrally on neurons in the arcuate nucleus and anteroventral periventricular area. In addition to appetite regulation, these hormones exert influences on spatially and functionally-related mechanisms regulating reproductive function, such as the kisspeptin-gonadotropin releasing hormone system. Negative energy balance often occurs partially as a result of strenuous and repetitive physical exercise. Exercise stress leads to increased cortisol secretion, but this action is mediated through the induced negative energy balance. In healthy adults with energy deficits, this exercise-induced stress appears to be more important than pure psychological stress in impairing reproductive function. Estrogen deficiency resulting from negative energy balance has important adverse effects on bone density as well as bone microarchitecture, and it may also adversely affect markers of cardiovascular disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Psychosocial dwarfism: psychopathological aspects and putative neuroendocrine markers.

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    Muñoz-Hoyos, Antonio; Molina-Carballo, Antonio; Augustin-Morales, Maríadelcarmen; Contreras-Chova, Francisco; Naranjo-Gómez, Ana; Justicia-Martínez, Fuensanta; Uberos, José

    2011-06-30

    There exists an extensive terminology for defining the situation of children who, in varying circumstances, suffer from affective deprivation (AD), within an unsatisfactory family situation or in institutions. Nevertheless, the neuroendocrine mechanisms (if they exist) determining it have yet to be identified. Our objective was to determine if specific neuroendocrine markers, all of them previously implicated in affective disorders, could be modified, and in which sense, in affective deprivation syndrome of the child. For this purpose, we studied three separate groups of children: (1) control group (CG); (2) children suffering from AD; and (3) children with non-organic failure to thrive (NOFT). In every case, we studied the serum levels of melatonin, serotonin, β-endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway tryptophan metabolites (both during the day and at night). Significantly, there was a conspicuous reduction in the levels of each of the neuroendocrine markers (melatonin, serotonin, β-endorphins and ACTH) in the group suffering from affective deficiency, a diminution which was even more noticeable in the group of patients presenting delayed growth. Furthermore, as also occurs in other affective disorders, there were corresponding modifications in the metabolisation of tryptophan. We report the existence of neuroendocrine mechanisms that are associated with the above-mentioned clinical manifestations in these patients, mechanisms that may underlie the close connection existing between AD syndrome and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise a single process, but one with a different evolutionary continuum of psychosocial dwarfism. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

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    David L. Wachter

    2014-01-01

    Full Text Available Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin. Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A. In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.

  5. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

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    Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas

    2014-01-01

    Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. PMID:24701575

  6. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

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    Masai, Kyohei; Tsuta, Koji; Kawago, Mitsumasa; Tatsumori, Takahiro; Kinno, Tomoaki; Taniyama, Tomoko; Yoshida, Akihiko; Asamura, Hisao; Tsuda, Hitoshi

    2013-07-01

    Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

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

    DEFF Research Database (Denmark)

    Adolf, Katja; Wagner, Ludwig; Bergh, Anders

    2007-01-01

    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...

  8. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

    OpenAIRE

    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 neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), a...

  9. Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products.

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    Layfield, L; Ulich, T; Liao, S; Barr, R; Cheng, L; Lewin, K L

    1986-08-01

    Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells.

  10. 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...... and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P epithelium (P

  11. Neuroendocrine pathways altered in autism. Special role of reelin.

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    Kelemenova, Silvia; Ostatnikova, Daniela

    2009-01-01

    Autism is the most genetically influenced neuropsychiatric disorder with heritability of approximately 90%. Since genetic factors seem to play a crucial role in autism etiology, enormous attention is focused on genetic analyses of the disorder. Reelin, one of the autism candidates, is necessary in regulation of neuronal migration during brain development and also in maintaining synaptic plasticity during postnatal life period. Reduced reelin levels were observed in sera and brain cortices of autistic patients. In this review, abnormalities in reelin signaling and the relationship between reelin deficiency and principal neuroendocrine pathways are discussed.

  12. 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 neuroendocr

  13. Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases

    Institute of Scientific and Technical Information of China (English)

    Gen-You Yao; Ji-Lin Zhou; Mao-De Lai; Xiao-Qing Chen; Pei-Hui Chen

    2003-01-01

    AIM: To investigate the incidence of neuroendocrine (NE)cells and their hormone products in adenocarcinomas and evaluate their significance in clinical pathology and prognosis.METHODS: By using tissue sectioning and immunocytochemistry, 356 cases of adenocarcinomas were studied to examine the presence of chromorgranin and polypeptide hormones in adenocarcinoma samples from our hospital.RESULTS: The positive rate of NE cells and hormone products was 41.5 % (54/130) and 59.3 % (32/54), respectively in large intestinal adenocarcinoma cases; 39.6 % (38/96) and 36.8 % (14/38), respectively in gastric cancer cases; 38.1%(8/21) and 50.0 % (4/8), respectively in prostatic cancer cases; 21.0 % (17/81) and 17.6 % (3/17), respectively in breasr cancer cases; 17.9 % (5/28) and 60.0 % (3/5),respectively in pancreatic cancer cases. Among carcinomas of large intestine, pancreas and breast, the highly differentiated NE cell numbers were higher than the poorly differentiated NE cell numbers; while the gastric carcinoma cases had more poorly differentiated NE cells than highly differentiated NE cells. The higher detection rate of NE cells and their hormone products, the higher 5-year survival rate among the large intestine cancer cases.CONCLUSION: Close correlation was observed between NE cells and their hormone products with the cancer differentiations. For colorectal carcinomas, there is a close correlation of the presence of NE cells and their hormone products with the tumor staging and prognosis.

  14. Chromogranin A as serum marker for gastroenteropancreatic neuroendocrine tumors: a single center experience and literature review.

    OpenAIRE

    Christoph J Auernhammer; Christine Spitzweg; Burkhard Göke; Hoffmann, Johannes N.; Herrmann, Karin A.; Alexander Haug; Michael Vogeser; Axel Kuttner; Michael Lauseker; Svenja Nölting

    2012-01-01

    The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA), urinary 5-hydroxyindoleacetic acid (5-HIAA) and alkaline phosphatase (AP) in neuroendocrine tumors (NETs) of the GastroEnteroPancreatic-(GEP-) system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62) and pancreatic (n = 48) NETs. CgA levels were analyzed b...

  15. Values of Seven Tumor Markers in Identiifcation and Diagnosis of Esophageal Carcinoma Accompanied by Neuroendocrine Differentiation

    Institute of Scientific and Technical Information of China (English)

    LIU Lian-ke; SHAO Ming-wen; MA Lan; SUN Jing; GUAN Dan; SHU Yongqian

    2015-01-01

    Objective:To explore the values of seven tumor markers in the identiifcation and diagnosis of esophageal carcinoma accompanied by neuroendocrine differentiation (E-NED). Methods:A total of 378 patients diagnosed as low differentiation of esophageal carcinoma in The First Affiliated Hospital with Nanjing Medical University from Jan., 2008 to Dec., 2013 were selected, in which there were 349 with esophageal carcinoma with no neuroendocrine differentiation (E-NNED, E-NNED group) and 29 with E-NED (E-NED group). The levels of seven tumor markers including synaptophysin (Syn), Chromogranin A (CgA), neuron-specific enolase (NSE), neural cell adhesion molecule (CD56), protein gene product 9.5 (PGP9.5), secretagogue (SCGN) and thyroid transcription factor-1 (TTF-1) of both groups were detected with histoimmunochemical method and the influences of the single and combined detection of above indexes on E-NED patients were analyzed. Results:Except TTF-1, expressions of Syn, CgA, NSE, CD56, PGP9.5 and SCGN in E-NED group were evidently higher than those in E-NNED group and the differences were significant (P Conclusion:PGP9.5 and SCGN can be used as neuroendocrine markers for the pathological diagnosis of E-NED and Syn + CD56, Syn + PGP9.5 and Syn + SCGN can all be used as combined detection.

  16. 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.

  17. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  18. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms.

    Science.gov (United States)

    Gordon, Jennifer L; Rubinow, David R; Thurston, Rebecca C; Paulson, Julia; Schmidt, Peter J; Girdler, Susan S

    2016-11-01

    Vasomotor symptoms (VMS) may be associated with an increased risk of cardiovascular disease. One candidate mechanism may involve alterations in physiological responses to stress. The current study therefore examined the relationship between self-reported VMS bother and cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses to an acute psychosocial stress protocol. One hundred eighty-six women in the menopausal transition or early postmenopausal stage (age 45-60 y) provided the data for this article. Subjective hot flash and night sweat bother were assessed using the Greene Climacteric Scale. Women also underwent a stressor battery involving a speech and a mental arithmetic task while cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses were assessed. Repeated measures regression analyses were used to examine the relationship between self-reported VMS and physiologic responses to the stressor. In multivariate analyses adjusting for potential confounders, self-reported hot flash bother was associated with lower overall cardiac index and stroke volume index and higher overall vascular resistance index and levels of the inflammatory cytokine interleukin-6. Hot flash bother also tended to be associated with higher overall cortisol levels and higher baseline levels of plasma norepinephrine. Night sweat bother, on the other hand, was associated with higher overall cortisol levels and tended to be associated with higher interleukin-6. Self-reported VMS bother is associated with an unfavorable hemodynamic and neuroendocrine profile characterized by increased hypothalamic-pituitary-adrenal axis and central sympathetic activation, inflammation, and vasoconstriction. Further research investigating this profile in relation to VMS, and the potential health implications of this association, is warranted.

  19. An intergenerational effect of neuroendocrine metabolic programming alteration induced by prenatal ethanol exposure in rats.

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    Kou, Hao; Shen, Lang; Luo, Han-Wen; Chen, Liao-Bin; Wu, Dong-Fang; Wang, Hui

    2017-09-12

    Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors.

    Science.gov (United States)

    Voortman, Johannes; Lee, Jih-Hsiang; Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Lucchi, Marco; Smith, William I; Meltzer, Paul; Wang, Yisong; Giaccone, Giuseppe

    2010-07-20

    The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

  1. Chromogranin A as Serum Marker for Gastroenteropancreatic Neuroendocrine Tumors: A Single Center Experience and Literature Review

    Directory of Open Access Journals (Sweden)

    Christoph J. Auernhammer

    2012-02-01

    Full Text Available The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA, urinary 5-hydroxyindoleacetic acid (5-HIAA and alkaline phosphatase (AP in neuroendocrine tumors (NETs of the GastroEnteroPancreatic-(GEP- system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62 and pancreatic (n = 48 NETs. CgA levels were analyzed by a commercially-available immunoradiometric assay (CIS-bio during routine follow-up in the years 2000–2009. CgA showed a higher sensitivity for midgut (68% than pancreatic (54% NETs. A higher CgA sensitivity and significantly higher median CgA values were found in patients with liver metastases than in those without, and in patients with hepatic and additionally extra-hepatic metastases than in those with hepatic and nodal metastases alone, respectively. We found an overall sensitivity for elevated 5HIAA excretion of 69% for midgut NETs and a significant correlation between median CgA and 5-HIAA values. The sensitivity of AP and the correlations of AP/CgA-data-pairs were low in both midgut and pancreatic NETs, although highest for metastatic pancreatic NETs. The sensitivity of CgA measurement depends on the NET primary location and spread of disease. 5-HIAA and CgA showed comparable sensitivity in midgut NETs, while AP does not seem to be useful as a tumor marker in GEP-NETs.

  2. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones.

    Science.gov (United States)

    Nobels, F R; Kwekkeboom, D J; Coopmans, W; Schoenmakers, C H; Lindemans, J; De Herder, W W; Krenning, E P; Bouillon, R; Lamberts, S W

    1997-08-01

    Chromogranin 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 neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may

  3. Stathmin in pancreatic neuroendocrine neoplasms: a marker of proliferation and PI3K signaling.

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    Schimmack, Simon; Taylor, Andrew; Lawrence, Ben; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Modlin, Irvin M; Kidd, Mark; Tang, Laura H

    2015-01-01

    Chromosome 1p35-36, which encodes tumor suppressors and mitotic checkpoint control genes, is commonly altered in human malignancies. One gene at this locus, stathmin 1 (STMN1), is involved in cell cycle progression and metastasis. We hypothesized that increased STMN1 expression may play a role in pancreatic neuroendocrine neoplasm (pNEN) malignancy. We investigated stathmin copy number variation, mRNA, and protein expression using PCR-Taqman Copy Number Assays, Q-PCR, Western blot, and immunohistochemistry. A mechanistic role for stathmin in proliferation was assessed in the BON cell line under growth-restrictive conditions and siRNA silencing. Furthermore, its role in PI3K signaling pathway activation was evaluated using pharmacological inhibitors. mRNA (p = 0.0001) and protein (p stathmin inactivation (dephosphorylation p stathmin was overexpressed and associated with pathological parameters in pancreatic NENs. We postulate that STMN1 overexpression and phosphorylation result in a loss of cell cycle mitotic checkpoint control and may render tumors amenable to PI3K inhibitory therapy.

  4. Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line.

    Science.gov (United States)

    Tesfazghi, Sara; Eide, Jacob; Dammalapati, Ajitha; Korlesky, Colin; Wyche, Thomas P; Bugni, Tim S; Chen, Herbert; Jaskula-Sztul, Renata

    2013-10-01

    Medullary thyroid cancer (MTC) is an aggressive neuroendocrine tumor (NET). Previous research has shown that activation of Notch signaling has a tumor suppressor role in NETs. The potential therapeutic effect of thiocoraline on the activation of the Notch pathway in an MTC cell line (TT) was investigated. Thiocoraline was isolated from a marine bacterium Verrucosispora sp. MTT assay (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide) was used to determine the IC50 value and to measure cell proliferation. Western blot revealed the expression of Notch isoforms, NET, and cell cycle markers. Cell cycle progression was validated by flow cytometry. The mRNA expression of Notch isoforms and downstream targets were measured using real-time PCR. The IC50 value for thiocoraline treatment in TT cells was determined to be 7.6 nmol/L. Thiocoraline treatment decreased cell proliferation in a dose- and time-dependent manner. The mechanism of growth inhibition was found to be cell cycle arrest in G1 phase. Thiocoraline activated the Notch pathway as demonstrated by the dose-dependent increase in mRNA and protein expression of Notch isoforms. Furthermore, treatment with thiocoraline resulted in changes in the expression of downstream targets of the Notch pathway (HES1, HES2, HES6, HEY1, and HEY2) and reduced expression of NET markers, CgA, and ASCL1. Thiocoraline is a potent Notch pathway activator and an inhibitor of MTC-TT cell proliferation at low nanomolar concentrations. These results provide exciting evidence for the use of thiocoraline as a potential treatment for intractable MTC.

  5. Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats

    Directory of Open Access Journals (Sweden)

    Bu Lihong

    2004-12-01

    protein (UCP-1 mRNA levels in brown adipose tissue (BAT were seen in Phyto-600 fed males. However, decreased core body temperature was recorded in these same animals compared to Phyto-free fed animals. Conclusions This study demonstrates that consumption of a soy-based (isoflavone-rich diet, significantly alters several parameters involved in maintaining body homeostatic balance, energy expenditure, feeding behavior, hormonal, metabolic and neuroendocrine function in male rats.

  6. 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.

  7. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

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    Voortman, Johannes; Lee, Jih-Hsiang; Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Lucchi, Marco; Smith, William I; Meltzer, Paul; Wang, Yisong; Giaccone, Giuseppe

    2010-01-01

    The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in ...

  8. Genetic alterations and markers of melanoma

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    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  9. Thymomas: a cytological and immunohistochemical study, with emphasis on lymphoid and neuroendocrine markers

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    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. [Value of the sleep EEG as a biological marker of depressive states. Comparison with 3 neuroendocrine tests].

    Science.gov (United States)

    Ansseau, M; Scheyvaerts, M; Doumont, A; Poirrier, R; Demonceau, G; Legros, J J; Franck, G

    1985-04-01

    In a sample of 12 endogenous depressive inpatients (8 primary and 4 secondary depressives), we compared the diagnostic usefulness of REM latency (recorded during at least 4 consecutive nights) with 3 neuroendocrine tests: dexamethasone suppression test and GH response after clonidine (a alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) challenges. Shortened REM latency (less than 50 min during at least 1 night) was present in 67% of depressives. However, REM latency presented a clear night to night intra-patient variability that makes it necessary to record at least 3 consecutive nights for the best sensitivity. Non-suppression after dexamethasone was present in 50% of depressives, blunted GH response after clonidine, in 75% and blunted response after apomorphine, in 42%. A total of 92% of patients exhibited at least one abnormal biological parameter (100% of primary and 75% of secondary depressives); 67% of patients exhibited at least two disturbed parameters and these patients constituted the whole primary depressive group (100%). These results show that these 4 potential biological markers of depression are not necessarily distributed in the same population. This suggests the potential usefulness of their concurrent use for improved accuracy of diagnosis.

  11. Brief mindfulness meditation training alters psychological and neuroendocrine responses to social evaluative stress.

    Science.gov (United States)

    Creswell, J David; Pacilio, Laura E; Lindsay, Emily K; Brown, Kirk Warren

    2014-06-01

    To test whether a brief mindfulness meditation training intervention buffers self-reported psychological and neuroendocrine responses to the Trier Social Stress Test (TSST) in young adult volunteers. A second objective evaluates whether pre-existing levels of dispositional mindfulness moderate the effects of brief mindfulness meditation training on stress reactivity. Sixty-six (N=66) participants were randomly assigned to either a brief 3-day (25-min per day) mindfulness meditation training or an analytic cognitive training control program. All participants completed a standardized laboratory social-evaluative stress challenge task (the TSST) following the third mindfulness meditation or cognitive training session. Measures of psychological (stress perceptions) and biological (salivary cortisol, blood pressure) stress reactivity were collected during the social evaluative stress-challenge session. Brief mindfulness meditation training reduced self-reported psychological stress reactivity but increased salivary cortisol reactivity to the TSST, relative to the cognitive training comparison program. Participants who were low in pre-existing levels of dispositional mindfulness and then received mindfulness meditation training had the greatest cortisol reactivity to the TSST. No significant main or interactive effects were observed for systolic or diastolic blood pressure reactivity to the TSST. The present study provides an initial indication that brief mindfulness meditation training buffers self-reported psychological stress reactivity, but also increases cortisol reactivity to social evaluative stress. This pattern may indicate that initially brief mindfulness meditation training fosters greater active coping efforts, resulting in reduced psychological stress appraisals and greater cortisol reactivity during social evaluative stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Altering Visual Perception Abnormalities: A Marker for Body Image Concern.

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    Francesca L Beilharz

    Full Text Available The body image concern (BIC continuum ranges from a healthy and positive body image, to clinical diagnoses of abnormal body image, like body dysmorphic disorder (BDD. BDD and non-clinical, yet high-BIC participants have demonstrated a local visual processing bias, characterised by reduced inversion effects. To examine whether this bias is a potential marker of BDD, the visual processing of individuals across the entire BIC continuum was examined. Dysmorphic Concern Questionnaire (DCQ; quantified BIC scores were expected to correlate with higher discrimination accuracy and faster reaction times of inverted stimuli, indicating reduced inversion effects (occurring due to increased local visual processing. Additionally, an induced global or local processing bias via Navon stimulus presentation was expected to alter these associations. Seventy-four participants completed the DCQ and upright-inverted face and body stimulus discrimination task. Moderate positive associations were revealed between DCQ scores and accuracy rates for inverted face and body stimuli, indicating a graded local bias accompanying increases in BIC. This relationship supports a local processing bias as a marker for BDD, which has significant assessment implications. Furthermore, a moderate negative relationship was found between DCQ score and inverted face accuracy after inducing global processing, indicating the processing bias can temporarily be reversed in high BIC individuals. Navon stimuli were successfully able to alter the visual processing of individuals across the BIC continuum, which has important implications for treating BDD.

  13. Relevant infrastructural alterations in a pancreatic neuroendocrine tumor: an insulinoma case.

    Science.gov (United States)

    Mirancea, Gabriel-Valeriu; Moroşanu, Ana-Maria; Carniciu, Simona; Dima, Simona; Bacalbaşa, Nicolae; Popescu, Irinel; Ionescu-Tîrgovişte, Constantin; Mirancea, Nicolae

    2014-01-01

    In this study, we focus our interest on some peculiar infrastructural abnormalities detected in an insulinoma case. Tumor pancreatic endocrine cells proliferated detrimental to exocrine counterpart, so that extensive areas of prevalent β-tumor cells can be seen. Two phenotypes of β-tumor cells can be identified: (1) β-tumor cells with full euchromatic and nucleolated nuclei and (2) β-tumor cells with heterochromatic and shrink nuclei. Because of stroma alteration, including basement membrane, cell-extracellular matrix junctions are also compromised. The mostly striking and important finding in this report for a case of insulinoma is the high fragility of plasma membrane of both two phenotypes of β-tumor cells. Cell-cell junctions, especially desmosomal junctions are severely altered, almost missing, plasma membranes showed shedding membrane vesicles and extensive dissolutions leading to pseudo-syncytia formation. Extravasated blood cells, including inflammatory cells contribute to the dramatic and extensive destructive areas of epithelial cells as well as stroma counterpart. Moreover, also the inner cell cytomembranes exhibit abnormalities: many β-tumor cells have excessive dilatations of nuclear envelope and endoplasmic reticulum. All above severe infrastructural abnormalities, especially down regulation of cell-cell and cell-extracellular matrix adhesions and plasma membranes fragility might result in aberrant cell behavior and, consequently, much care should be taken for the postoperatory patient evolution.

  14. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  15. Renal neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Brian R Lane

    2009-01-01

    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  16. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

    DEFF Research Database (Denmark)

    Christensen, Lene Svendstrup; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    , a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

  17. Differentiation in neuroblastoma: diffusion-limited hypoxia induces neuro-endocrine secretory protein 55 and other markers of a chromaffin phenotype.

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    Fredrik Hedborg

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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. 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. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells

    Science.gov (United States)

    Pifano, Marina; Garona, Juan; Capobianco, Carla S.; Gonzalez, Nazareno; Alonso, Daniel F.; Ripoll, Giselle V.

    2017-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated

  20. 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

  1. 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...... airways compared to controls, indicating that the rise in PGP9.5 in the airway epithelium is related to downregulation of p27(Kip1). This study is the first to specifically identify the carcinogen naphthalene as an inducer of PGP9.5 expression in non-neuroendocrine epithelium after acute lung injury...... and carcinogenesis. We investigated the expression of PGP9.5 in mice in response to two prominent carcinogens found in tobacco smoke: Naphthalene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). By immunostaining, we found that PGP9.5 protein was highly expressed throughout the airway epithelium in the days...

  2. Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman

    Directory of Open Access Journals (Sweden)

    Elham S. Al-Risi

    2017-09-01

    Full Text Available Objectives: To evaluate the significance of serum chromogranin A (CgA status in patients with and without different neuroendocrine tumors (NETs by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. Methods: We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014. During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11–86 years and mean±standard deviation (SD 44.0±18.0 years, were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. Results: Of the 302 CgA tests reviewed, 197 (65.2% were within the quoted normal range; however, 105 (34.8% had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5% had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3% patients with CgA > 22 IU/L (83.0±116.0 IU/L who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus. Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L. The overall clinical sensitivity of CgA in the

  3. Transcriptome Alterations Following Developmental Atrazine Exposure in Zebrafish Are Associated with Disruption of Neuroendocrine and Reproductive System Function, Cell Cycle, and Carcinogenesis

    Science.gov (United States)

    Freeman, Jennifer L.

    2013-01-01

    Atrazine, a herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies, is implicated as an endocrine-disrupting chemical (EDC) and potential carcinogen. Studies show that EDCs can cause irreversible changes in tissue formation, decreased reproductive potential, obesity, and cancer. The U.S. Environmental Protection Agency considers an atrazine concentration of ≤ 3 ppb in drinking water safe for consumption. The specific adverse human health effects associated with a developmental atrazine exposure and the underlying genetic mechanisms of these effects are not well defined. In this study, zebrafish embryos were exposed to a range of atrazine concentrations to establish toxicity. Morphological, transcriptomic, and protein alterations were then assessed at 72h postfertilization following developmental atrazine exposure at 0, 0.3, 3, or 30 ppb. A significant increase in head length was observed in all three atrazine treatments. Transcriptomic profiles revealed 21, 62, and 64 genes with altered expression in the 0.3, 3, and 30 ppb atrazine treatments, respectively. Altered genes were associated with neuroendocrine and reproductive system development, function, and disease; cell cycle control; and carcinogenesis. There was a significant overlap (42 genes) between the 3 and 30 ppb differentially expressed gene lists, with two of these genes (CYP17A1 and SAMHD1) present in all three atrazine treatments. Increased transcript levels were translated to significant upregulation in protein expression. Overall, this study identifies genetic and molecular targets altered in response to a developmental atrazine exposure to further define the biological pathways and mechanisms of toxicity. PMID:23358194

  4. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl S; Wolstenholme, Jennifer T; 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

  5. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich;

    2009-01-01

    Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (ptumors...

  6. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (ptumors...

  7. Biochemistry of neuroendocrine tumours.

    Science.gov (United States)

    de Herder, Wouter W

    2007-03-01

    Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.

  8. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  9. Neuroendocrine mechanisms in athletes.

    Science.gov (United States)

    Misra, Madhusmita

    2014-01-01

    Athletic activity may be associated with alterations in various neuroendocrine axes depending on the state of energy availability. In addition, genetic factors and an underlying predilection for polycystic ovarian syndrome (PCOS) may predispose some athletes to develop functional hypothalamic amenorrhea earlier than other athletes. In conditions of low energy availability associated with athletic activity, changes that occur in various neuroendocrine axes are primarily adaptive, and aim to either conserve energy for the most essential functions, or allow the body to draw on its reserves to meet energy needs. These hormonal changes, however, then lead to changes in body composition and bone metabolism. Impaired bone accrual in younger athletes and low bone density in older athletes constitutes the major pathologic consequence of neuroendocrine changes associated with low energy availability. The female athlete triad of low energy availability, menstrual dysfunction, and low bone density is prevalent in certain kinds of sports and activities, particularly endurance sports, gymnastics, and ballet. It is essential to screen for this condition in athletes at every preparticipation physical and during office visits, and to put in place an effective treatment team to manage the triad early, in order to optimize outcomes.

  10. 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 previo

  11. The FGFR4-G388R single-nucleotide polymorphism alters pancreatic neuroendocrine tumor progression and response to mTOR inhibition therapy.

    Science.gov (United States)

    Serra, Stefano; Zheng, Lei; Hassan, Manal; Phan, Alexandria T; Woodhouse, Linda J; Yao, James C; Ezzat, Shereen; Asa, Sylvia L

    2012-11-15

    Pancreatic neuroendocrine tumors (pNET), also known as islet cell tumors, exhibit a wide range of biologic behaviors ranging from long dormancy to rapid progression. Currently, there are few molecular biomarkers that can be used to predict recurrence/metastasis or response to therapy. This study examined the predictive and prognostic value of a single nucleotide polymorphism substituting an arginine (R) for glycine (G) in codon 388 of the FGFR4 transmembrane domain. We established the FGFR4 genotype of 71 patients with pNETs and correlated genotype with biologic behavior. We created an in vivo model of pNET with BON1 cells and transfected them with either FGFR4-G388 or FGFR4-R388 to determine the mechanism of action and to examine response to the mTOR inhibitor everolimus. We then validated the predictive results of experimental studies in a group of patients treated with everolimus. FGFR4-R388 is associated with more aggressive clinical behavior in patients with pNETs with a statistically significant higher risk of advanced tumor stage and liver metastasis. Using an orthotopic mouse xenograft model, we show that FGFR4-R388 promotes tumor progression by increasing intraperitoneal spread and metastatic growth within the liver. Unlike FGFR4-G388, FGFR4-R388 BON1 tumors exhibited diminished responsiveness to everolimus. Concordantly, there was a statistically significant reduction in response to everolimus in patients with FGFR4-R388. Our findings highlight the importance of the FGFR4 allele in pNET progression and identify a predictive marker of potential therapeutic importance in this disease.

  12. Neuroendocrine evaluation of cardiac disease.

    Science.gov (United States)

    Sisson, D David

    2004-09-01

    Current evidence favors the view that regardless of etiology, there is a predictable sequence of neuroendocrine activation that operates in most dogs and cats with progressive heart disease and that it is largely, but not entirely, independent of etiology. The natriuretic peptides and sympathetic nervous system seem to be early responders to developing cardiac and hemodynamic perturbations in both species. BNP plays a particularly prominent role in cats, possibly as a reflection of disease etiology. Shortly thereafter, plasma endothelin concentrations rise, reflecting the impact of the hemodynamic alterations on the vasculature. Endothelin and the natriuretic peptides directly suppress plasma renin release but have divergent effects on aldosterone. Activation of the tissue RAAS may operate early on to further the progression of heart failure, but evidence of plasma RAAS activation occurs comparatively late and near the time of development of overt CHF. Finally, in animals with severe CHF that are prone to hypotension,vasopressin levels may also rise, contributing to the retention of free water and congestion that is refractory to diuretics. Although oversimplified, this scenario seems to be consistent with data obtained in human, canine, and feline patients. These observations provide some impetus for evaluating ACE inhibitors in cats and beta-receptor-blocking drugs in dogs and cats. Perhaps we are also a little closer to identifying useful biochemical markers that can aid in the diagnosis of heart disease, guide therapy, and improve our understanding of the biologic processes occurring in our patients. Copyright 2004 Elsevier Inc.

  13. Functional Maturation of Neuroendocrine Gonadal Axis is Altered by Specific Phase Relations of Circadian Neurotransmitter Activity in Japanese Quail

    Institute of Scientific and Technical Information of China (English)

    DORISPHILLIPS; CHANDRAMOHINICHATURVEDI

    1995-01-01

    The preset study was designed to ascertain the effects of temporal relationship of circadian neural oscillations on puberty attainment and reproductive growth of Japances Quail,Coturnix coturnix japonica,Serotonin and dopamine precursors(5-hydroxytryptophan,5-HTP and L-dihydroxyphenylalanine,L-DOPA,5mg/100g body weight)were injected daily,8and 12h apart in two groups of one-day ld chick,while cotrols received two daily injections of normal saline.Weekly/biweekly observations(body weight,cloacal gland size,testicular volume and activity,ovarian follicular diameter and rate of egg production)were made until 9 weeks of age,when the experiment was terminated.Results indicate that 8 h relationship completely suppressed gonadal growth even under long photoperiod(LD16:8),while a 12 h relationship induced precocious sexual maturity and increased the rate of reproductin(spermatogenesis and egg production).It is concluded that circadian phase relationship of serotonergic and dopaminergic activity may not only determine the onset of reproduction in this pultry species,but may also alter the rate of reproduction possibly by affecting photoperiodic mechanism of reproductive regulation.

  14. [Neuroendocrine immunomodulation].

    Science.gov (United States)

    Uchakin, P N; Uchakina, O N; Tobin, B V; Ershov, F I

    2007-01-01

    Close interaction between the immune and nervous systems is well documented. The ability of immunocompetent cells to express receptors to neuroendocrine mediators as well as secrete many of them is proved. The current literature suggests that the hormones of the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonodal axes play the most significant role in the regulation of immune responsiveness. On the other hand, the immune system communicates with the CNS directly through the cytokines that are able to cross the blood-brain barrier, or directly via the nervus vagus, as well as via secondary messengers. Receptors to a number of cytokines have been found in the nervous tissue. Moreover, glial cells are able to secrete cytokines in the amount significant enough for at least autocrine action. In this article, the authors review the role of the "major" stress hormones such as cortisol, DHEA, growth hormone in the regulation of immune response, as well as neuro- and psychotropic properties of two major groups of cytokines that support cell-mediated (Type 1) and humoral (Type 2) immune reactions. This review emphasizes neuro-endocrine-immune interactions in response to infection both under laboratory and clinical conditions.

  15. 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 United States are diagnosed with Merkel cell skin cancer each year. Almost all people diagnosed with the ...

  16. [Neuroendocrine neoplasms of the breast].

    Science.gov (United States)

    Anlauf, M; Neumann, M; Bomberg, S; Luczak, K; Heikaus, S; Gustmann, C; Antke, C; Ezziddin, S; Fottner, C; Pavel, M; Pape, U-F; Rinke, A; Lahner, H; Schott, M; Cremer, B; Hörsch, D; Baum, R P; Groh, U; Alkatout, I; Rudlowski, C; Scheler, P; Zirbes, T K; Hoffmann, J; Fehm, T; Gabbert, H E; Baldus, S E

    2015-05-01

    Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

  17. Consensus on biomarkers for neuroendocrine tumour disease

    Science.gov (United States)

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James

    2016-01-01

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  18. Neuroendocrine-immune circuits, phenotypes, and interactions.

    Science.gov (United States)

    Ashley, Noah T; Demas, Gregory E

    2017-01-01

    Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and non-human animal models for many decades by the biomedical community, but ecological and evolutionary perspectives are lacking. Neuroendocrine-immune interactions can be conceptualized using a series of feedback loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can exert profound influences on these phenotypes, which can in turn reciprocally modulate behavior. For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors can impinge upon neuroendocrine-immune interactions. One classic example is the immunocompetence handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators of traits important for female choice while suppressing the immune system. Reciprocally, neuroendocrine-immune pathways can promote the development of altered behavioral states, such as sickness behavior. Understanding the energetic signals that mediate neuroendocrine-immune crosstalk is an active area of research. Although the field of psychoneuroimmunology (PNI) has begun to explore this crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus has been relatively underappreciated in comparative species. The field of ecoimmunology, while traditionally emphasizing the study of non-model systems from an ecological evolutionary perspective, often under natural conditions, has focused less on the physiological mechanisms underlying behavioral responses. This review summarizes neuroendocrine-immune interactions using a comparative framework to understand the ecological and evolutionary forces that shape these complex physiological interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Neuroendocrine responses to hypoglycemia.

    Science.gov (United States)

    Tesfaye, Nolawit; Seaquist, Elizabeth R

    2010-11-01

    The counterregulatory response to hypoglycemia is a complex and well-coordinated process. As blood glucose concentration declines, peripheral and central glucose sensors relay this information to central integrative centers to coordinate neuroendocrine, autonomic, and behavioral responses and avert the progression of hypoglycemia. Diabetes, both type 1 and type 2, can perturb these counterregulatory responses. Moreover, defective counterregulation in the setting of diabetes can progress to hypoglycemia unawareness. While the mechanisms that underlie the development of hypoglycemia unawareness are not completely known, possible causes include altered sensing of hypoglycemia by the brain and/or impaired coordination of responses to hypoglycemia. Further study is needed to better understand the intricacies of the counterregulatory response and the mechanisms contributing to the development of hypoglycemia unawareness.

  20. Neuroendocrine gastric carcinoma expressing somatostatin: A highly malignant, rare tumor

    Institute of Scientific and Technical Information of China (English)

    Jaques Waisberg; Leandro Luongo de Matos; Ana Maria do Amaral Antonio Mader; Sérgio Pezzolo; Esmeralda Miristene Eher; Vera Luiza Capelozzi; Manlio Basilio Speranzini

    2006-01-01

    Poorly differentiated gastric neuroendocrine carcinomas,although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.

  1. [Neuroendocrine carcinoma of the ampullar region with oat-cell histological features and adenocarcinoma].

    Science.gov (United States)

    Fresno, M F; Floriano, P; Díaz Iglesias, J M; Ablanedo, P; Pérez del Río, M J; Barneo, L; Herrero, A

    1997-01-01

    We report a case of primary duodenal carcinoma showing neuroendocrine and glandular differentiation, in a 65-years-old male. Both components were closely related and transition between them was observed. The neuroendocrine component was composed of an undifferentiated "oat-cell" type, with positive immunostaining for neuroendocrine and epithelial markers. Ultrastructural findings confirmed this double differentiation, with dense cytoplasmatic granules of neurosecretory type. The neuroendocrine component showed greater aggressiveness with lymph node metastasis.

  2. Conformational altered p53 as an early marker of oxidative stress in Alzheimer's disease.

    Science.gov (United States)

    Buizza, Laura; Cenini, Giovanna; Lanni, Cristina; Ferrari-Toninelli, Giulia; Prandelli, Chiara; Govoni, Stefano; Buoso, Erica; Racchi, Marco; Barcikowska, Maria; Styczynska, Maria; Szybinska, Aleksandra; Butterfield, David Allan; Memo, Maurizio; Uberti, Daniela

    2012-01-01

    In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named "unfolded p53", was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients.

  3. Conformational altered p53 as an early marker of oxidative stress in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Laura Buizza

    Full Text Available In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD and subjects harboured AD related mutation (ADmut, were used. Oxidative stress was evaluated measuring i the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD, glutathione peroxidase (GPx and glutathione reductase (GRD. We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named "unfolded p53", was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt and PAb240 (that is direct towards unfolded p53, and followed by the immunoblotting with anti-4-hydroxynonenal (HNE and anti- 3-nitrotyrosine (3NT antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients.

  4. The alteration of zinc transporter gene expression is associated with inflammatory markers in obese women.

    Science.gov (United States)

    Noh, Hwayoung; Paik, Hee Young; Kim, Jihye; Chung, Jayong

    2014-04-01

    Obesity, a chronic inflammatory state, is associated with altered zinc metabolism. ZnT and Zip transporters are involved in the regulation of zinc metabolism. This study examined the relationships among obesity, zinc transporter gene expression, and inflammatory markers in young Korean women. The messenger RNA (mRNA) levels of leukocyte zinc transporters between obese (BMI = 28.3 ± 0.5 kg/m(2), n = 35) and nonobese (BMI = 20.7 ± 0.2 kg/m(2), n = 20) women aged 18-28 years were examined using quantitative real-time polymerase chain reaction. Inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6, were measured in serum by enzyme immunoassay. ZnT1 and Zip1 were the most abundantly expressed zinc transporters in leukocytes. The mRNA levels of many zinc transporters (ZnT4, ZnT5, ZnT9, Zip1, Zip4, and Zip6) were significantly lower in obese women, and expression of these genes was inversely correlated with BMI and body fat percentage. In addition, inflammatory markers (CRP and TNF-α) were significantly higher in obese women. The mRNA levels of ZnT4, Zip1, and Zip6 were inversely correlated with CRP (P zinc transporters such as ZnT4, ZnT5, Zip1, and Zip6 (P zinc transporters may be altered in obese individuals. Changes in zinc transporters may also be related to the inflammatory state associated with obesity.

  5. Alterations of T-cell surface markers in older women with persistent human papillomavirus infection

    Science.gov (United States)

    Rodríguez, Ana Cecilia; García-Piñeres, Alfonso J; Hildesheim, Allan; Herrero, Rolando; Trivett, Matthew; Williams, Marcus; Atmella, Ivannia; Ramírez, Margarita; Villegas, Maricela; Schiffman, Mark; Burk, Robert; Freer, Enrique; Bonilla, José; Bratti, Concepción; Pinto, Ligia A

    2012-01-01

    We previously reported decreased lymphocyte proliferative responses among older women with persistent human papillomavirus (HPV) infection. To characterize the phenotype of peripheral lymphocytes associated with persistent HPV infection, we evaluated the expression of different cell surface markers in peripheral blood mononuclear cells (PBMCs) from a case-control study within a 10,049-woman population-based cohort study in Guanacaste, Costa Rica. Women in the cohort aged 46 to 74 and with HPV results at their 5th year anniversary visit were considered, and all women (n=87) with persistent HPV infections, all women (n=196) with transient HPV infections and a random sample of HPV DNA-negative women (n=261) frequency-matched to cases on age were selected for this study. A median of 3 years after the case-control matching visit, cervical cells were collected for liquid-based cytology and repeat HPV DNA genotyping. Blood was obtained from which PBMCs were extracted and cryopreserved for immunological phenotyping via flow cytometry. Significant increases in risk of HPV persistence were observed for three marker subsets indicative of immune cell activation/differentiation. Relative risk estimates were 5.4 (95%CI=2.2–13.3) for CD69+CD4+, 2.6 (95%CI=1.2–5.9) for HLADR+CD3+CD4+ and 2.3 (95%CI=1.1–4.7) for CD45RO+CD27−CD8+. A significant decrease in HPV persistence was observed for a subset marker indicative of an immature, undifferentiated memory state CD45RO+CD27+CD4+ (OR=0.36; 95%CI = 0.17–0.76). Adjustment for these markers only partially explained the previously reported association between decreased lymphoproliferative responses and persistent HPV infection. Whether phenotypic alterations observed predispose to HPV persistence or result from it should be the focus of future studies. PMID:20473864

  6. Stress-induced alteration of left ventricular eccentricity: An additional marker of multivessel CAD.

    Science.gov (United States)

    Gimelli, Alessia; Liga, Riccardo; Giorgetti, Assuero; Casagranda, Mirta; Marzullo, Paolo

    2017-03-28

    Abnormal left ventricular (LV) eccentricity index (EI) is a marker of adverse cardiac remodeling. However, the interaction between stress-induced alterations of EI and major cardiac parameters has not been explored. We sought to evaluate the relationship between LV EI and coronary artery disease (CAD) burden in patients submitted to myocardial perfusion imaging (MPI). Three-hundred and forty-three patients underwent MPI and coronary angiography. LV ejection fraction (EF) and EI were computed from gated stress images as measures of stress-induced functional impairment. One-hundred and thirty-six (40%), 122 (35%), and 85 (25%) patients had normal coronary arteries, single-vessel CAD, and multivessel CAD, respectively. Post-stress EI was lower in patients with multivessel CAD than in those with normal coronary arteries and single-vessel CAD (P = 0.001). This relationship was confirmed only in patients undergoing exercise stress test, where a lower post-stress EI predicted the presence of multivessel CAD (P = 0.039). Post-stress alterations of LV EI on MPI may unmask the presence of multivessel CAD.

  7. Alternative poladenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Anders eRehfeld

    2014-04-01

    Full Text Available The tumorigenesis of small intestinal neuroendocrine tumors is poorly understood. Recent studies have associated alternative polyadenylation with proliferation, cell transformation and cancer. Polyadenylation is the process in which the pre-mRNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo alternative polyadenylation. This produces two or more distinct mRNA isoforms with different 3’ untranslated regions. Additionally, alternative polyadenylation can also produce mRNAs containing different 3’-terminal coding regions. Therefore, alternative polyadenylation 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 small intestinal neuroendocrine tumors and a reference sample. In the tumors sixteen genes showed significant changes of alternative polyadenylation pattern, which lead to either the 3’ truncation of mRNA coding regions or 3’ untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1 and DACT2. We validated the alternative polyadenylation in 3 out of 3 cases with Q-RT-PCR. Our findings suggest that changes of alternative polyadenylation pattern in these 16 genes could be involved in the tumorigenesis of small intestinal neuroendocrine tumors. Furthermore, they also point to alternative polyadenylation as a new target for both diagnostic and treatment of small intestinal neuroendocrine tumors. The identified genes with alternative polyadenylation specific to the small intestinal neuroendocrine tumors could be further tested as diagnostic markers and drug targets for disease prevention and treatment.

  8. Previous hypertensive disease of pregnancy is associated with alterations of markers of insulin resistance.

    Science.gov (United States)

    Girouard, Joël; Giguère, Yves; Moutquin, Jean-Marie; Forest, Jean-Claude

    2007-05-01

    Insulin resistance syndrome has been observed in women with hypertensive disease of pregnancy, but few studies evaluated the presence of the syndrome a few years after delivery. The objective of this study was to evaluate the presence of insulin resistance and its metabolic alterations in these women compared with those who had a normal pregnancy. We performed an observational study in 168 women with previous hypertensive disease of pregnancy and 168 control subjects with normal pregnancy contacted, on average, 7.8 years after their first delivery (mean age: 34.8 years). Complete blood lipid profile, insulin, glucose, homocysteine, adipokins, and markers of inflammation were measured. Also, an oral glucose tolerance test was performed in 146 case and 135 control subjects. Case subjects were more overweight compared with control subjects. We found significantly lower high-density lipoprotein cholesterol and adiponectin levels and higher apolipoprotein (apo) apoB/apoA1 ratio, homocysteine, leptin, and insulin levels among case subjects compared with control subjects (Phypertensive disease of pregnancy show signs of insulin resistance within the first decade after delivery. These findings suggest that insulin resistance may be the link between hypertensive disease of pregnancy and increased cardiovascular risk later in life.

  9. Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1α.

    Directory of Open Access Journals (Sweden)

    Elizabeth K Lucas

    Full Text Available Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α in the pathophysiology of Huntington Disease (HD. Adult PGC-1α (-/- mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α (-/- mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α (-/- mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α (-/- mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α (-/- striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α (-/- mice show increases in the expression of medium spiny neuron (MSN markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning.

  10. 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.

  11. 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.

  12. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs......, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however...

  13. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

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    Spitkovsky Dimitry

    2004-08-01

    Full Text Available Abstract Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis. However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is

  14. A rare case report of a primary large-cell neuroendocrine carcinoma of the breast with coexisting Paget disease.

    Science.gov (United States)

    Psoma, Elizabeth; Nikolaidou, Olga; Stavrogianni, Thomai; Mavromati, Areti; Lytras, Konstantinos; Xirou, Persefoni; Koumbanaki, Melanie; Panagiotopoulou, Dimitra

    2012-01-01

    Neuroendocrine carcinomas are malignancies deriving from neuroendocrine cells existing in various sites of the body, most commonly in the lungs and gastrointestinal tract. Primary neuroendocrine carcinomas of the breast are extremely rare, and their diagnosis is confirmed by positive neuroendocrine markers. We describe a case of a 46-year-old woman with a palpable mass in her left breast for the previous 3 months. The tumor was resected and a primary large-cell neuroendocrine tumor of the breast was confirmed by histopathologic examination. Paget disease of the nipple was noted as well.

  15. Power spectrum scale invariance as a neural marker of cocaine misuse and altered cognitive control

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    Jaime S. Ide

    2016-01-01

    Conclusions: These findings suggest disrupted connectivity dynamics in the fronto-parietal areas in association with post-signal behavioral adjustment in cocaine addicts. These new findings support PSSI as a neural marker of impaired cognitive control in cocaine addiction.

  16. Neuroendocrine Tumor, diagnostic difficulties

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    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.

  17. 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

  18. Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes

    DEFF Research Database (Denmark)

    Cangemi, Claudia; Skov, Vibe; Poulsen, Michael Kjaer

    2011-01-01

    Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.......Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined....

  19. Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

    DEFF Research Database (Denmark)

    Thorup, A K; Reibel, J; Schiødt, M

    1998-01-01

    for the transformation of a premalignant into a malignant lesion. The aim of this study was to examine if expression of specific cell adhesion molecules can be used as markers of malignant development. By immunohistochemistry, we examined the expression pattern of integrins alpha2beta1, alpha3beta1, alpha6beta4...

  20. 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...

  1. Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

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    Fatemeh Abharzanjani

    2017-01-01

    Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

  2. Acute physiological stress promotes clustering of synaptic markers and alters spine morphology in the hippocampus.

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    Veronica Sebastian

    Full Text Available GluA2-containing AMPA receptors and their association with protein kinase M zeta (PKMζ and post-synaptic density-95 (PSD-95 are important for learning, memory and synaptic plasticity processes. Here we investigated these synaptic markers in the context of an acute 1h platform stress, which can disrupt spatial memory retrieval for a short-term memory on the object placement task and long-term memory retrieval on a well-learned radial arm maze task. Acute stress increased serum corticosterone and elevated the expression of synaptic PKMζ while decreasing synaptic GluA2. Using co-immunoprecipitation, we found that this stressor promotes the clustering of GluA2, PKMζ and PSD-95, which is consistent with effects reported from overexpression of PKMζ in cell culture. Because PKMζ overexpression has also been shown to induce spine maturation in culture, we examined how stress impacts synaptic markers within changing spines across various hippocampal subfields. To achieve this, we employed a new technique combining Golgi staining and immmunohistochemistry to perform 3D reconstruction of tertiary dendrites, which can be analyzed for differences in spine types and the colocalization of synaptic markers within these spines. In CA1, stress increased the densities of long-thin and mushroom spines and the colocalization of GluA2/PSD-95 within these spines. Conversely, in CA3, stress decreased the densities of filopodia and stubby spines, with a concomitant reduction in the colocalization of GluA2/PSD-95 within these spines. In the outer molecular layer (OML of the dentate gyrus (DG, stress increased both stubby and long-thin spines, together with greater GluA2/PSD-95 colocalization. These data reflect the rapid effects of stress on inducing morphological changes within specific hippocampal subfields, highlighting a potential mechanism by which stress can modulate memory consolidation and retrieval.

  3. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.

    Science.gov (United States)

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2015-08-20

    We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise

  4. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

    OpenAIRE

    Spitkovsky Dimitry; Bliev Alexander; Golovina Darya; Krutikova Ella; Frank Georgy; Andreeva Yulia; Zavalishina Larisa; Volgareva Galina; Ermilova Valeriya; Kisseljov Fjodor

    2004-01-01

    Abstract Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less ...

  5. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish.

  6. Alteration of neurotrophin and cytokine expression in lymphocytes as novel peripheral markers of spatial memory deficits induced by prenatal stress.

    Science.gov (United States)

    Pascuan, C G; Di Rosso, M E; Pivoz-Avedikian, J E; Wald, M R; Zorrilla Zubilete, M A; Genaro, A M

    2017-05-01

    Much evidence has suggested that early life adversity can have a lasting effect on behavior. The aim of this study was to explore the impact of prenatal exposure to stress on cognition in adult life and how it impacts chronic stress situations. In addition, we investigated the participation of glucocorticoids, neurotrophins and cytokines in prenatal stress effects. For this purpose, pregnant mice were placed in a cylindrical restraint tube for 2h daily during the last week of pregnancy. Control pregnant females were left undisturbed during their entire pregnancy period. Object-in-place task results showed that adult female mice exposed to prenatal stress exhibited an impairment in spatial memory. However, in the alternation test this memory deficit was only found in prenatally stressed mice submitted to chronic stress. This alteration occurred in parallel with a decrease in BDNF, an increase in glucocorticoid receptors and an alteration of Th1/Th2 in the hippocampus. Interestingly, these changes were observed in peripheral lymph nodes as well. However, none of the mentioned changes were observed in adult male mice. These results indicate that lymphoid cells could be good candidates as peripheral markers of susceptibility to behavioral alterations associated with prenatal exposure to stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. First-trimester screening markers are altered in pregnancies conceived after IVF/ICSI

    DEFF Research Database (Denmark)

    Gjerris, A C; Loft, A; Pinborg, A

    2009-01-01

    -A multiples of the median value was significantly decreased when compared with that of pregnancies conceived spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the group treated by frozen embryo replacement. There was no difference in the level of free beta-human chorionic gonadotropin......OBJECTIVES: To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in a large national population of women pregnant after assisted reproductive technology (ART), in order to decide whether...... or not to correct risk calculation for mode of conception. METHODS: A national prospective cohort study of 1000 pregnancies achieved after ART was compared with a control group of 2543 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Risk calculation...

  8. Altered monocyte activation markers in Tourette’s syndrome: a case–control study

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    Matz Judith

    2012-05-01

    Full Text Available Abstract Background Infections and immunological processes are likely to be involved in the pathogenesis of Tourette’s syndrome (TS. To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. Methods In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha, interleukin 6 (IL-6, soluble CD14 (sCD14, IL1-receptor antagonist (IL1-ra, and serum neopterin were detected by immunoassays. Results We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. Conclusions The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

  9. Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

    Directory of Open Access Journals (Sweden)

    Rimorini Laura

    2010-10-01

    Full Text Available Abstract Aim To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT upon vascular contractility. Methods Adult male Wistar rats were fed a commercial diet without (CD or with 10% fructose (FRD in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Results Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS, nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. Conclusions FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

  10. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  11. Prenatal ultrasound screening: false positive soft markers may alter maternal representations and mother-infant interaction.

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    Sylvie Viaux-Savelon

    Full Text Available BACKGROUND: In up to 5% of pregnancies, ultrasound screening detects a "soft marker" (SM that places the foetus at risk for a severe abnormality. In most cases, prenatal diagnostic work-up rules out a severe defect. We aimed to study the effects of false positive SM on maternal emotional status, maternal representations of the infant, and mother-infant interaction. METHODOLOGY AND PRINCIPAL FINDINGS: Utilizing an extreme-case prospective case control design, we selected from a group of 244 women undergoing ultrasound, 19 pregnant women whose foetus had a positive SM screening and a reassuring diagnostic work up, and 19 controls without SM matched for age and education. In the third trimester of pregnancy, within one week after delivery, and 2 months postpartum, we assessed anxiety, depression, and maternal representations. Mother-infant interactions were videotaped during feeding within one week after delivery and again at 2 months postpartum and coded blindly using the Coding Interactive Behavior (CIB scales. Anxiety and depression scores were significantly higher at all assessment points in the SM group. Maternal representations were also different between SM and control groups at all study time. Perturbations to early mother-infant interactions were observed in the SM group. These dyads showed greater dysregulation, lower maternal sensitivity, higher maternal intrusive behaviour and higher infant avoidance. Multivariate analysis showed that maternal representation and depression at third trimester predicted mother-infant interaction. CONCLUSION: False positive ultrasound screenings for SM are not benign and negatively affect the developing maternal-infant attachment. Medical efforts should be directed to minimize as much as possible such false diagnoses, and to limit their psychological adverse consequences.

  12. Altered Sputum Microstructure as a Marker of Airway Obstruction in Cystic Fibrosis Patients

    Science.gov (United States)

    Duncan, Gregg; Jung, James; West, Natalie; Boyle, Michael; Suk, Jung Soo; Hanes, Justin

    In the lungs of cystic fibrosis (CF) patients, highly viscoelastic mucus remains stagnant in the lung leading to obstructed airways prone to recurrent infections. Bulk-fluid rheological measurement is primarily used to assess the pathological features of mucus. However, this approach is limited in detecting microscopic properties on the length scale of pathogens and immune cells. We have shown in prior work based on the transport of muco-inert nanoparticles (MIP) in CF sputum that patients can carry significantly different microstructural properties. In this study, we aimed to determine the factors leading to variations between patients in sputum microstructure and their clinical implications. The microrheological properties of CF sputum were measured using multi-particle tracking experiments of MIP. MIP were made by grafting polyethylene glycol onto the surface of polystyrene nanoparticles which prior work has shown prevents adhesion to CF sputum. Biochemical analyses show that sputum microstructure was significantly altered by elevated mucin and DNA content. Reduction in sputum pore size is characteristic of patients with obstructed airways as indicated by measured pulmonary function tests. Our microstructural read-out may serve as a novel biomarker for CF.

  13. Biological characteristics of breast carcinomas with neuroendocrine cell differentiation

    Institute of Scientific and Technical Information of China (English)

    姚根有; 周吉林; 赵仲生; 阮俊

    2004-01-01

    Background The aim of this study was to investigate DNA content and expression of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast carcinomas with neuroendocrine (NE) cell differentiation.Methods Chromogranin, c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected immunohistochemically. Classic Feulgen staining image analysis techniques were used to quantify DNA content in 81 of the breast cancer samples.Results The c-erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both significantly lower than that in breast carcinomas without neuroendocrine cells (62.6% and 68.7%, respectively, P 5c aneuploidy cells, and rate of aneuploidy among cells were all lower than that in NE (-) breast carcinomas (P<0.01). In NE (+) grade I or II breast carcinomas, these indices were also all lower than that in the NE (-) breast carcinoma samples (P<0.01).Conclusion Breast carcinomas with neuroendocrine differentiation have a lower rate of malignancy. Neuroendocrine differentiation could serve as a prognostic marker in clinical practice.

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

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    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.

  15. Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria.

    Science.gov (United States)

    Schönfeld, P; Struy, H

    1999-08-27

    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling.

  16. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    Science.gov (United States)

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  17. Neuroendocrine control of metabolism.

    Science.gov (United States)

    Kuliczkowska-Plaksej, J; Milewicz, A; Jakubowska, J

    2012-03-01

    Metabolism is controlled through homeostatic system consisting of central centers, gut hormones, hormones from adipose tissue and the other hormonal axes. This cooperation is based on cross-talk between central and peripheral signals. Among them the hypothalamus plays a crucial role, with interconnected nuclei forming neuronal circuits. Other regions in the brain, such as the brain stem, the endocannabinoid system, the vagal afferents, are also involved in energy balance. The second component is peripheral source of signals--the gastrointestinal tract hormones. Additionally, adipokines from adipose tissue, thyrotropic, gonadotropic and somatotropic axes play a role in energy homeostasis. Knowledge about all components of this neuroendocrine circuit will be helpful in developing novel therapeutic approaches against the metabolic syndrome and its components.

  18. 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.

  19. Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys.

    Science.gov (United States)

    Kiguchi, Norikazu; Ding, Huiping; Peters, Christopher M; Kock, Nancy D; Kishioka, Shiroh; Cline, J Mark; Wagner, Janice D; Ko, Mei-Chuan

    2017-01-01

    Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6). By using RT-qPCR, we found that mRNA expression levels of both GFAP and IBA1 were up-regulated in the spinal dorsal horn (SDH) of diabetic monkeys compared with non-diabetic monkeys. Among all chemokines, expression levels of three chemokine ligand-receptor systems, i.e., CCL2-CCR2, CCL3-CCR1/5, and CCL4-CCR5, were up-regulated in the SDH of diabetic monkeys. Moreover, in the SDH, seven additional chemokine receptors, i.e., CCR4, CCR6, CCR8, CCR10, CXCR3, CXCR5, and CXCR6, were also up-regulated in diabetic monkeys. In contrast, expression levels of MOP, KOP, and DOP, but not NOP receptors, were down-regulated in the SDH of diabetic monkeys, and the thalamus had fewer changes in the glial markers, chemokines and opioids. These findings indicate that neuroinflammation, manifested as glial activation and simultaneous up-regulation of multiple chemokine ligands and receptors, seems to be permanent in type 2 diabetic monkeys. As chemokines and opioids are important pain modulators, this first-in-primate study provides a translational bridge for determining the functional efficacy of spinal drugs targeting their signaling cascades.

  20. Neuroendocrine Immunoregulation in Multiple Sclerosis

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    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.

  1. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases.

    Science.gov (United States)

    Berber, Eren; Flesher, Nora; Siperstein, Allan E

    2002-08-01

    We previously reported on the safety and efficacy of laparoscopic radiofrequency thermal ablation (RFA) for treating hepatic neuroendocrine metastases. The aim of this study is to report our 5-year RFA experience in the treatment of these challenging group of patients. Of the 222 patients with 803 liver primary and secondary tumors undergoing laparoscopic RFA between January 1996 and August 2001, a total of 34 patients with 234 tumors had neuroendocrine liver metastases. There were 25 men and 9 women with a mean +/- SEM age of 52 +/- 2 years who underwent 42 ablations. Primary tumor types included carcinoid tumor in 18 patients, medullary thyroid cancer in 7, secreting islet cell tumor in 5, and nonsecreting islet cell tumor in 4. There was no mortality, and the morbidity was 5%. The mean hospital stay was 1.1 days. Symptoms were ameliorated in 95%, with significant or complete symptom control in 80% of the patients for a mean of 10+ months (range 6-24 months). All patients were followed for a mean +/- SEM of 1.6 +/- 0.2 years (range 1.0-5.4 years). During this period new liver lesions developed in 28% of patients, new extrahepatic disease in 25%, and local liver recurrence in 13%; existing liver lesions progressed in 13%. Overall 41% of patients showed no progression of their cancer. Nine patients (27%) died. Mean +/- SEM survivals after diagnosis of primary disease, detection of liver metastases, and performance of RFA were 5.5 +/- 0.8 years, 3.0 +/- 0.3 years, and 1.6 +/- 0.2 years, respectively. Sixty-five percent of the patients demonstrated a partial or significant decrease in their tumor markers during follow-up. In conclusion, RFA provides excellent local tumor control with overnight hospitalization and low morbidity in the treatment of liver metastases from neuroendocrine tumors. It is a useful modality in the management of these challenging group of patients.

  2. Protection of hepatotoxicity using Spondias pinnata by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers in Wistar rats

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    Shoaib Shadab Iqbal

    2016-12-01

    Conclusion: S. pinnata extracts AE and EE possess a potent hepatoprotective effect against ethanol-induced liver injury in Wistar rats, and protect them from hepatotoxicity by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers.

  3. Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor.

    Science.gov (United States)

    Iwata, Ryoichi; Maruyama, Masato; Ito, Tomoki; Nakano, Yosuke; Kanemura, Yonehiro; Koike, Taro; Oe, Souichi; Yoshimura, Kunikazu; Nonaka, Masahiro; Nomura, Shosaku; Sugimoto, Tetsuo; Yamada, Hisao; Asai, Akio

    2017-05-17

    Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.

  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. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring

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    Clare M. Reynolds

    2017-09-01

    Full Text Available Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut–brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  6. The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

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    Ather MH

    2012-11-01

    devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences – in particular, the role of changing miRNA expression – provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy.Keywords: prostate cancer, epigenetic, genetic, neuroendocrine differentiation

  7. Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

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    Watanabe Hiromitsu

    2010-06-01

    Full Text Available Abstract Background Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1 is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions. Methods An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia. Results DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2/spasmolytic polypeptide-expressing metaplasia (SPEM emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM. Conclusion The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic

  8. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

    OpenAIRE

    Barbara Seroczyńska; Patrycja Koszałka; Zofia Woźniak; Tomasz Bączek; Anna Lewczuk; Ilona Olędzka; Natalia Miękus; Jarosław Skokowski; Alina Plenis

    2013-01-01

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnos...

  9. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    Science.gov (United States)

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

  10. CSF markers of Alzheimer’s pathology and microglial activation are associated with altered white matter microstructure in asymptomatic adults at risk for Alzheimer’s disease

    Science.gov (United States)

    Melah, Kelsey E; Lu, Sharon Yuan-Fu; Hoscheidt, Siobhan M; Alexander, Andrew L; Adluru, Nagesh; Destiche, Daniel J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C; Gleason, Carey E; Dowling, N Maritza; Bratzke, Lisa C; Rowley, Howard A; Sager, Mark A; Asthana, Sanjay; Johnson, Sterling C; Bendlin, Barbara B

    2015-01-01

    Background The immune response in Alzheimer’s disease (AD) involves activation of microglia which may remove β-amyloid. However, overproduction of inflammatory compounds may exacerbate neural damage in Alzheimer’s disease. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. Objective To determine whether neuroinflammation exacerbates neural damage in preclinical AD. Methods We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age=60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. Results Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. Conclusion Inflammation may play a role in neural damage in preclinical AD. PMID:26836182

  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...... and gastrointestinal tract combined with positive neuroendocrine immunohistochemical markers. While much information has been gathered during the last decade, most studies suffer from poor statistics due to a low incidence, and there are still fundamental open questions regarding etiology and prognosis. Furthermore...

  12. Expression of a neuroendocrine gene signature in gastric tumor cells from CEA 424-SV40 large T antigen-transgenic mice depends on SV40 large T antigen.

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    Fritz Ihler

    Full Text Available BACKGROUND: A large fraction of murine tumors induced by transgenic expression of SV40 large T antigen (SV40 TAg exhibits a neuroendocrine phenotype. It is unclear whether SV40 TAg induces the neuroendocrine phenotype by preferential transformation of progenitor cells committed to the neuroendocrine lineage or by transcriptional activation of neuroendocrine genes. METHODOLOGY/PRINCIPAL FINDINGS: To address this question we analyzed CEA424-SV40 TAg-transgenic mice that develop spontaneous tumors in the antral stomach region. Immunohistology revealed expression of the neuroendocrine marker chromogranin A in tumor cells. By ELISA an 18-fold higher level of serotonin could be detected in the blood of tumor-bearing mice in comparison to nontransgenic littermates. Transcriptome analyses of antral tumors combined with gene set enrichment analysis showed significant enrichment of genes considered relevant for human neuroendocrine tumor biology. This neuroendocrine gene signature was also expressed in 424GC, a cell line derived from a CEA424-SV40 TAg tumor, indicating that the tumor cells exhibit a similar neuroendocrine phenotype also in vitro. Treatment of 424GC cells with SV40 TAg-specific siRNA downregulated expression of the neuroendocrine gene signature. CONCLUSIONS/SIGNIFICANCE: SV40 TAg thus appears to directly induce a neuroendocrine gene signature in gastric carcinomas of CEA424-SV40 TAg-transgenic mice. This might explain the high incidence of neuroendocrine tumors in other murine SV40 TAg tumor models. Since the oncogenic effect of SV40 TAg is caused by inactivation of the tumor suppressor proteins p53 and RB1 and loss of function of these proteins is commonly observed in human neuroendocrine tumors, a similar mechanism might cause neuroendocrine phenotypes in human tumors.

  13. Mild stress induces brain region-specific alterations of selective ER stress markers' mRNA expression in Wfs1-deficient mice.

    Science.gov (United States)

    Altperery, A; Raud, S; Sütt, S; Reimets, R; Visnapuu, T; Toots, M; Vasar, E

    2017-09-26

    In this work, the effect of mild stress (elevated plus maze test, EPM) on the expression of endoplasmic reticulum (ER) stress markers in different brain areas of wild type (WT) and Wfs1-deficient (Wfs1KO) mice was investigated. The following ER stress markers were studied: activating transcription factor 6α (Atf6α), protein kinase-like ER kinase (Perk), X-box binding protein 1 (Xbp1) and its spliced form (Xbp1s), 78-kilodalton glucose regulated protein (Grp78), 94-kilodalton glucose regulated protein (Grp94), C/EBP homologous protein (Chop). Wfs1KO and WT mice, not exposed to EPM, had similar patterns of ER stress markers in the studied brain areas. The exploratory activity of Wfs1KO mice in the EPM was inhibited compared to WT mice, probably reflecting increased anxiety in genetically modified mice. In response to the EPM, activation of inositol-requiring transmembrane kinase and endonuclease 1α (Ire1α) ER stress pathway was seen in both genotypes, but in different brain areas. Such a brain region-specific Ire1α activation was linked with dominant behavioural trends in these mice as more anxious, neophobic Wfs1KO mice had increased ER stress markers expression in the temporal lobe, the brain region related to anxiety, and more curious WT mice had ER stress markers increased in the ventral striatum which is related to the exploratory drive. The molecular mechanism triggering respective changes in ER stress markers in these brain regions is likely related to altered levels of monoamine neurotransmitters (serotonin, dopamine) in Wfs1KO mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Notch Signaling in Neuroendocrine Tumors

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    Judy Sue Crabtree

    2016-04-01

    Full Text Available Carcinoids and neuroendocrine tumors (NETs are a heterogeneous group of tumors that arise from the neuroendocrine cells of the GI tract, endocrine pancreas and the respiratory system. NETs remain significantly understudied with respect to molecular mechanisms of pathogenesis, particularly the role of cell fate signaling systems like Notch. The abundance of literature on the Notch pathway is a testament to its complexity in different cellular environments. Notch receptors can function as oncogenes in some contexts, and tumor suppressors in others. The genetic heterogeneity of NETs suggests that to fully understand the roles and the potential therapeutic implications of Notch signaling in NETs, a comprehensive analysis of Notch expression patterns and potential roles across all NET subtypes is required.

  15. Neuroendocrine abnormalities in Parkinson's disease.

    Science.gov (United States)

    De Pablo-Fernández, Eduardo; Breen, David P; Bouloux, Pierre M; Barker, Roger A; Foltynie, Thomas; Warner, Thomas T

    2017-02-01

    Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research.

  16. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

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    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.

  17. 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...

  18. 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.

  19. [Neuroendocrine neoplasms of the mediastinum].

    Science.gov (United States)

    Brcic, L; Heidinger, M; Popper, H

    2016-09-01

    Primary neuroendocrine tumors (NET) in the mediastinum are very rare and among them thymic NETs are the most common. They represent 5 % of all thymic and mediastinal tumors. The WHO classification from 2015 subdivides thymic NETs into three groups; low grade (typical carcinoid), intermediate grade (atypical carcinoid) and high grade (large cell neuroendocrine carcinoma and small cell carcinoma). Through this change of mediastinal/thymic NET classification into three groups of malignancy, the nomenclature was adapted to that of the lungs, while the histological criteria for each entity remained the same. Thymic NETs typically occur in middle-aged adults and predominantly in males. Approximately 30 % are asymptomatic and the rest present with symptoms caused by local tumor growth, distant metastases and/or endocrine manifestations. Carcinoids can also occur as a part of multiple endocrine neoplasia type 1 (MEN1) and at the time of diagnosis commonly present with regional lymph node or distant metastases, which most often affect the lungs and bones. For the correct diagnosis tumor cell morphology, mitotic count and/or necrosis are crucial. Patients with typical carcinoids have the best prognosis, whereas the prognosis is slightly worse for atypical carcinoids but very poor for large cell neuroendocrine carcinomas. Small cell carcinomas have the worst prognosis and the shortest median survival time of approximately 14 months.

  20. NOTCH SIGNALLING MODULATES HYPOXIA-INDUCED NEUROENDOCRINE DIFFERENTIATION OF HUMAN PROSTATE CANCER CELLS

    Science.gov (United States)

    Danza, Giovanna; Di Serio, Claudia; Rosati, Fabiana; Lonetto, Giuseppe; Sturli, Niccolò; Kacer, Doreen; Pennella, Antonio; Ventimiglia, Giuseppina; Barucci, Riccardo; Piscazzi, Annamaria; Prudovsky, Igor; Landriscina, Matteo; Marchionni, Niccolò; Tarantini, Francesca

    2012-01-01

    Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation has been associated with tumor progression, poor prognosis and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavourable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells, in vitro. Results exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent down regulation of Notch-mediated signalling, as demonstrated by reduced levels of the Notch target genes, Hes1 and Hey1. Neuroendocrine differentiation was promoted by attenuation of Hes1 transcription, as cells expressing a dominant negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia down regulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen independent cell lines, PC3 and Du145, it did not change the extent of NE differentiation in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Conclusions hypoxia induces neuroendocrine differentiation of LNCaP cells in vitro, which appears to be driven by the inhibition of Notch signalling with subsequent down-regulation of Hes1 transcription. PMID:22172337

  1. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress

    Directory of Open Access Journals (Sweden)

    Sarah J Spencer

    2013-06-01

    Full Text Available Feeding behavior is closely regulated by neuroendocrine mechanisms that can be influenced by stressful life events. However, the feeding response to stress varies among individuals with some increasing and others decreasing food intake after stress. In addition to the impact of acute lifestyle and genetic backgrounds, the early life environment can have a life-long influence on neuroendocrine mechanisms connecting stress to feeding behavior and may partially explain these opposing feeding responses to stress. In this review I will discuss the perinatal programming of adult hypothalamic stress and feeding circuitry. Specifically I will address how early life (prenatal and postnatal nutrition, early life stress, and the early life hormonal profile can program the hypothalamic-pituitary-adrenal (HPA axis, the endocrine arm of the body’s response to stress long-term and how these changes can, in turn, influence the hypothalamic circuitry responsible for regulating feeding behavior. Thus, over- or under-feeding and / or stressful events during critical windows of early development can alter glucocorticoid (GC regulation of the HPA axis, leading to changes in the GC influence on energy storage and changes in GC negative feedback on HPA axis-derived satiety signals such as corticotropin-releasing-hormone. Furthermore, peripheral hormones controlling satiety, such as leptin and insulin are altered by early life events, and can be influenced, in early life and adulthood, by stress. Importantly, these neuroendocrine signals act as trophic factors during development to stimulate connectivity throughout the hypothalamus. The interplay between these neuroendocrine signals, the perinatal environment, and activation of the stress circuitry in adulthood thus strongly influences feeding behavior and may explain why individuals have unique feeding responses to similar stressors.

  2. GEP-NET : rare tumour connections. Pathophysiological aspects of gastroenteropancreatic neuroendocrine tumours

    NARCIS (Netherlands)

    Kuiper, Patricia

    2011-01-01

    Clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) varies strikingly, both in terms of symptoms and outcome. An understanding of the basic biology unique to GEP-NETs is necessary for optimum management of patients with these complex tumors. Although markers for GEP-NETs ex

  3. 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 different

  4. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

    Science.gov (United States)

    Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

    2016-06-01

    The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

  5. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G;

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  6. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Neuroendocrine Hyperplasia of Infancy.

    Science.gov (United States)

    Carr, Laurie L; Kern, Jeffrey A; Deutsch, Gail H

    2016-09-01

    Although incidental reactive pulmonary neuroendocrine cell hyperplasia (PNECH) is seen on biopsy specimens in adults with chronic lung disease, disorders characterized by marked PNECH are rare. Primary hyperplasia of neuroendocrine cells in the lung and obstructive lung disease related to remodeling or physiologic constriction of small airways define diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) in the adult and neuroendocrine cell hyperplasia of infancy (NEHI) in children. DIPENCH and NEHI share a similar physiology, typical imaging appearance, and increased neuroendocrine cells on biopsy. However, there are important differences related to the underlying disease mechanisms leading to disparate outcomes.

  7. Neuroendocrine carcinomas arising in ulcerative colitis: coincidences or possible correlations?

    Science.gov (United States)

    Grassia, Roberto; Bodini, Paolo; Dizioli, Paolo; Staiano, Teresa; Iiritano, Elena; Bianchi, Guglielmo; Buffoli, Federico

    2009-09-07

    Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis (UC) and Crohn's disease, but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel. With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group of tumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids (NENs) are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immunohistochemical staining for neuroendocrine markers: a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age (35 years vs 77 years) and disease duration (11 years vs 27 years), and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD, NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial, goblet, Paneth and neuroendocrine cells. It has yet to be established which IBD patients have a higher risk of developing NENs.

  8. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significance of alt...

  9. 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...

  10. Neuroendocrine Tumor of the Appendix in Children.

    Science.gov (United States)

    Wu, Hao; Chintagumpala, Murali; Hicks, John; Nuchtern, Jed G; Okcu, M Fatih; Venkatramani, Rajkumar

    2017-03-01

    Neuroendocrine tumor (NET) of the appendix is the most common gastrointestinal epithelial tumor in children. The utility of serum markers or the indication for hemicolectomy has not been established in children. In 45 children diagnosed with appendiceal NET, 89% NETs were incidentally found following appendectomy performed for suspected acute appendicitis. The median age was 12 years, and 56% patients were female. Postoperative somatostatin scan (n=5), serum chromogranin A (n=4), and urine 5-HIAA (n=9) were all within normal limits. Pathology slides of 35 patients showed mesoappendiceal invasion in 29% patients, and vascular invasion in 6% patients. Seven patients (16%) underwent hemicolectomy for invasion of mesoappendix (n=5), tumor near the resection margin (n=1), and tumor size 1.5 cm with vascular invasion (n=1). Only 2 hemicolectomy specimens showed disease: one in the appendiceal stump and the other as a micrometastasis in a mesenteric lymph node. There were no recurrences and all patients were alive and without evidence of disease at last follow-up. Pediatric appendiceal NET tends to have a benign clinical course with excellent prognosis. In the absence of carcinoid syndrome, postoperative scans and serum biomarkers do not seem to be useful. With completely resected tumors, the indication for hemicolectomy is unclear.

  11. 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...... be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later....

  12. Calcitonin-negative primary neuroendocrine tumor of the thyroid (nonmedullary) in a dog

    Science.gov (United States)

    Arias, E.A. Soler; Castillo, V.A.; Aristarain, M.E. Caneda

    2016-01-01

    The Calcitonin-negative neuroendocrine tumor of the thyroid (CNNET) or “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 expression for calcitonin. An Argentine dogo bitch showed a solid, compact thyroid tumor, which was IHC negative for the expression of calcitonin, carcinoembryonic antigen, thyroglobulin and S100 protein, and positive for synaptophysin and cytokeratin AE1-AE3. The Ki-67 proliferation index was low. We cite this case not only because it is the first case report of calcitonin-negative primary neuroendocrine tumor of the thyroid in dogs but also because we want to highlight the diagnostic importance of IHC in this regard. PMID:27928520

  13. Calcitonin-negative primary neuroendocrine tumor of the thyroid (nonmedullary in a dog

    Directory of Open Access Journals (Sweden)

    E.A. Soler Arias

    2016-11-01

    Full Text Available The Calcitonin-negative neuroendocrine tumor of the thyroid (CNNET or "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 expression for calcitonin. An Argentine dogo bitch showed a solid, compact thyroid tumor, which was IHC negative for the expression of calcitonin, carcinoembryonic antigen, thyroglobulin and S100 protein, and positive for synaptophysin and cytokeratin AE1-AE3. The Ki-67 proliferation index was low. We cite this case not only because it is the first case report of calcitonin-negative primary neuroendocrine tumor of the thyroid in dogs but also because we want to highlight the diagnostic importance of IHC in this regard.

  14. Effect of milk hydrolysates on inflammation markers and drug-induced transcriptional alterations in cell-based models

    DEFF Research Database (Denmark)

    Nielsen, Ditte Søvsø Gundelund; Theil, Peter Kappel; Larsen, Lotte Bach

    2012-01-01

    , or 60 min) were investigated in intestinal epithelial cells treated with the NSAID indomethacin. The bioactivity was evaluated as transcriptional alterations of transforming growth factor-β1 (TGF-β1), cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor κ...... with the hydrolysate treated with pepsin only. Hydrolysate prepared by corolase treatment for 60 min after pepsin hydrolysis downregulated transcription of COX-2 (P PPAR-γ was not affected (P > 0.05). Additionally...

  15. Biomarkers in Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Maria Serafeim Theochari

    2014-03-01

    Full Text Available The aim of biomarkers is to identify patients most likely to benefit from a therapeutic strategy. Pancreatic neuroendocrinetumors are rare neoplasms that arise in the endocrine tissues of the pancreas. Pancreatic neuroendocrine tumors represent3% of primary pancreatic neoplasms and their incidence has risen. The SMAD4 gene is located on chromosome 18q andsomeday the SMAD4 gene status may be useful for prognostic stratification and therapeutic decision. The cells respond toenvironmental signals by modulating the expressions of genes contained within the nucleus, when genes are activated aretranscribed to generate messenger RNA (mRNA. The examination of multiple expressed genes and proteins provides moreuseful information for prognostication of individual tumors. Here we summarize and discuss findings presented at the 2014ASCO Gastrointestinal Cancers Symposium. Anna Karpathakis et al. (Abstract #212 reported data about the role of DNAmethylation in gastrointestinal neuroendocrine tumors. Christina Lynn Roland et al. (Abstract #250 looked the impact OfSMAD4 on oncologic outcomes. Bong Kynn Kang et al. (Abstract #251 investigated prognostic biomarker using microRNAarray technology.

  16. Cutaneous metastasis of neuroendocrine carcinoma of the larynx: report of a case.

    Science.gov (United States)

    Ottinetti, A; Colombo, E; Dardano, F; Migliora, P; Picciotto, F; Zaccagna, A; Angeli, G

    2003-09-01

    Cutaneous metastasis from neuroendocrine carcinomas of visceral origin is rarely described in indexed literature. The primary sites of origin include: lung (Wick et al., J Am Acad Dermatol 1985; 13: 134), larynx (Zambruno et al., Ann Dermatol Venereol 1989; 116: 855; Schmidt et al., J Laryngol Otol 1994; 108: 272; Guerzider et al., Ann Pathol 1991; 11 (4): 253), mediastinum (Yoshimasu et al., J Dermatol 2001; 28 (3): 168), uterus (Fogaca et al., J Cutan Pathol 1993; 20: 455), and thymus (Wick et al., J Am Acad Dermatol 1985; 13: 134). In this report, the authors present the clinical, histological, immunohistochemical, and ultrastructural characteristics of secondary skin localizations of a neuroendocrine laryngeal tumor that occurred in a 61-year-old man. The complete follow up of the case is described and a brief revision of the terminology and classification of neuroendocrine neoplasms of the larynx is discussed, since a significant relationship exists between the degree of differentiation and biological behavior. On histological examination, the secondary cutaneous localization appeared to be more dedifferentiated compared to the primary tumor. The immunohistochemical patterns of reactivity were similar in both neoplasms, showing expression of neuroendocrine and epithelial markers. An important issue of prognostic significance is to differentiate a cutaneous metastasis of a neuroendocrine carcinoma from the primary small cell-undifferentiated carcinoma of the skin (Merkel cell carcinoma).

  17. Primary Hepatic Neuroendocrine Tumor with Unusual Thyroid Follicular-Like Morphologic Characteristics

    Science.gov (United States)

    Ibrahim, Mohd Elmugtaba; Abadeer, Kerolos; Zhai, Qihui (Jim)

    2017-01-01

    We describe a primary hepatic neuroendocrine tumor of a 57-year-old Thai woman who presented in 2004 with a suspicious mass in the left hepatic lobe. She underwent left hepatectomy for the 10.5-cm mass, called intermediate grade neuroendocrine carcinoma of unknown origin, likely metastatic. The tumor recurred in 2007, then called recurrent primary hepatic neuroendocrine tumor (PHNET), and the patient underwent liver transplant. Because of similarity between the neuroendocrine tumor and a thyroid tumor—specifically, follicular-like characteristics—immunohistochemical stains for thyroglobulin, TTF1, and calcitonin were performed. However, all were negative. All imaging studies revealed no evidence of a primary lesion other than the liver mass. In 2008, the patient's liver transplant failed because of ischemic cholangiopathy, and she underwent a second liver transplant. Seven years later, in 2015, she presented with metastatic neuroendocrine tumor of intermediate grade to the lung, consistent with metastatic PHNET. She underwent left upper-lobe wedge resection to remove the tumor. The patient is alive with no evidence of disease at 13 years after initial diagnosis. This rare variant of PHNET had thyroid-like morphologic characteristics but there is no evidence of primary thyroid tumor or thyroid markers in the primary and recurrent hepatic tumors and lung metastasis.

  18. Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas.

    Science.gov (United States)

    Linnoila, R I; Mulshine, J L; Steinberg, S M; Funa, K; Matthews, M J; Cotelingam, J D; Gazdar, A F

    1988-12-01

    Bronchial carcinoids and small cell lung cancer (SCLC) are currently recognized as neuroendocrine (NE) neoplasms. However, non-SCLC (NSCLC) may also express NE properties. Paraffin-embedded sections of a comprehensive panel of 113 lung carcinomas were analyzed for the expression of three general markers common to all NE cells, namely, chromogranin A, Leu-7 and neuron-specific enolase (NSE), five specific NE secretory products, and four other tumor markers by immunohistochemistry using the sensitive avidin-biotinylated peroxidase technique. The authors were able to demonstrate the following: (1) most, but not all carcinoids and SCLCs expressed multiple NE markers in a high percentage of tumor cells; (2) up to a half of NSCLC cases contained small subpopulations of cells expressing NE in a high percentage of tumor cells; (2) up to half of NSCLC cases contained small subpopulations of cells expressing NE markers; and (3) occasional NSCLCs showed staining patterns indistinguishable from SCLC. Specifically, 7 of 77 NSCLCs expressed four or more NE markers. NE markers in NSCLCs were more commonly expressed in adenocarcinomas and large cell carcinomas and rarely in squamous cell carcinomas. For comparison, the mean number of NE markers expressed by all cases of NSCLC was 1.5, carcinoids 6.0, and SCLCs 3.8. Individual "marker counts" were not useful in categorizing lung tumors as carcinoids and SCLC versus NSCLC. Instead, 95% of the tumors were correctly classified, applying a statistical model created from staining indices of the three general NE markers (chromogranin A, Leu-7, NSE) and three other tumor markers (carcinoembryonic antigen, keratin, vimentin). Because NSCLCs with NE features might have different clinical characteristics than other NSCLCs, immunohistochemistry provides an effective manner to identify this biologically interesting subset of NSCLCs in routine paraffin sections.

  19. Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection

    Institute of Scientific and Technical Information of China (English)

    Ingolf Schiefke; Andreas Fach; Marcus Wiedmann; Andreas V. Aretin; Eva Schenker; Gudrun Borte; Manfred Wiese; Joachim Moessner

    2005-01-01

    AIM: Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers.METHODS: Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30)or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured.RESULTS: BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN: 0.76 (0.53-0.99); LS:0.96 (0.62-1.23) g/cm2). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P = 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean 7-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P = 0.09).CONCLUSION: There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.

  20. Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation.

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2015-03-11

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune-brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region-specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches.

  1. Altered gene expression and repressed markers of autophagy in skeletal muscle of insulin resistant patients with type 2 diabetes

    Science.gov (United States)

    Møller, Andreas Buch; Kampmann, Ulla; Hedegaard, Jakob; Thorsen, Kasper; Nordentoft, Iver; Vendelbo, Mikkel Holm; Møller, Niels; Jessen, Niels

    2017-01-01

    This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and to determine associated signaling pathways. Gene expression profiles were examined by whole transcriptome, strand-specific RNA-sequencing and associated signaling was determined by western blot. We identified 117 differentially expressed gene transcripts. Ingenuity Pathway Analysis related these differences to abnormal muscle morphology and mitochondrial dysfunction. Despite a ~5-fold difference in plasma insulin, we did not observe any difference in phosphorylation of AKT or AS160, although other insulin-sensitive cascades, as mTOR/4EBP1, had retained their sensitivity. Autophagy-related gene (ATG14, RB1CC1/FIP200, GABARAPL1, SQSTM1/p62, and WIPI1) and protein (LC3BII, SQSTM1/p62 and ATG5) expression were decreased in skeletal muscle from the patients, and this was associated with a trend to increased phosphorylation of the insulin-sensitive regulatory transcription factor FOXO3a. These data show that gene expression is highly altered and related to mitochondrial dysfunction and abnormal morphology in skeletal muscle from severely insulin resistant patients with T2D, and that this is associated with decreased expression of autophagy-related genes and proteins. We speculate that prolonged treatment with high doses of insulin may suppress autophagy thereby generating a vicious cycle maintaining insulin resistance. PMID:28252104

  2. Neuroendocrine hormone amylin in diabetes

    Institute of Scientific and Technical Information of China (English)

    Xiao-Xi; Zhang; Yan-Hong; Pan; Yan-Mei; Huang; Hai-Lu; Zhao

    2016-01-01

    The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and cosecreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20 G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes.

  3. Large cell neuroendocrine carcinoma of the parotid gland: case report and literature review.

    Science.gov (United States)

    Casas, Pablo; Bernáldez, Ricardo; Patrón, Mercedes; López-Ferrer, Pilar; García-Cabezas, Miguel A

    2005-03-01

    A 74-year-old male presented with a large polinodular mass in the neck. Fine needle aspiration cytology (FNAC) showed an undifferentiated large cell carcinoma. Computed tomography (CT) showed a large parotid mass with multiple satelite nodules. The remaining radiological studies were normal. Radical parotidectomy was performed. The tumor was a large cell carcinoma with neuroendocrine features and positive immunostain for neuroendocrine markers. The patient received postoperative radiotherapy and was free of tumor eight months later. Only four cases of large cell neuroendocrine carcinoma (LCNEC) of the salivary gland have been communicated. All of them have involved the parotid gland. This tumor presents in elderly patients as a large infiltrating parotid mass. Fine needle aspiration cytology serves to recognize the carcinoma, but it fails in recognizing the neuroendocrine features of the tumor. The histopathological features of this tumor are the same as in other organs. Chromogranin and synaptophysin are useful immunohistochemical markers. A primary location of the tumor in another organ, specially the lung, should be ruled out. Surgery is the main treatment modality and can be complemented with postoperative radiotherapy. The prognosis seems to be poor. More studies are needed to better define the therapeutical alternatives and prognostic factors of these rare tumors.

  4. Management of pulmonary neuroendocrine tumors.

    Science.gov (United States)

    Ramirez, Robert A; Chauhan, Aman; Gimenez, Juan; Thomas, Katharine E H; Kokodis, Ioni; Voros, Brianne A

    2017-09-04

    Neuroendocrine tumors (NETs) of the lung are divided into 4 major types: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC) or typical carcinoid (TC). Each classification has distinctly different treatment paradigms, making an accurate initial diagnosis essential. The inconsistent clinical presentation of this disease, however, makes this difficult. The objective of this manuscript is to detail the diagnosis and management of the well differentiated pulmonary carcinoid (PC) tumors. A multidisciplinary approach to work up and treatment should be utilized for each patient. A multimodal radiological work-up is used for diagnosis, with contrast enhanced CT predominantly utilized and functional imaging techniques. A definitive diagnosis is based on tissue findings. Surgical management remains the mainstay of therapy and can be curative. In those with advanced disease, medical treatments consist of somatostatin analog (SSA) therapy, targeted therapy, chemotherapy or peptide receptor radionuclide therapy. SSAs are the standard of care in those with metastatic NETs, using either Octreotide long acting repeatable (LAR) or lanreotide as reasonable options, despite a scarcity of prospective data in PCs. Targeted therapies consist of everolimus which is approved for use in PCs, with various studies showing mixed results with other targeted agents. Additionally, radionuclide therapy may be used and has been shown to increase survival and to reduce symptoms in some studies. Prospective trials are needed to determine other strategies that may be beneficial in PCs as well as sequencing of therapy. Successful diagnosis and optimal treatment relies on a multidisciplinary approach in patients with lung NETs. Clinical trials should be used in appropriate patients.

  5. 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.

  6. Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1α Expression and Atrophy Markers.

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    Jill A Rahnert

    Full Text Available Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1α and overexpression of PGC-1α counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2, is a positive modulator of PGC-1α transcription. We previously reported that PGC-1α expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation, suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1α expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h to induce atrophy. Dex decreased PGC-1α mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA was decreased whereas SIK was increased. To assess PGC-1α transcription, muscle cells were transfected with a PGC-1α luciferase reporter plasmid (PGC-1α-Luc. Dex suppressed PGC-1α luciferase activity while both isobutylmethylxanthine (IBMX and over-expression of CRTC1 or CRTC2 increased PGC-1α-Luc activity. Mutation of the CRE binding site from PGC-1α-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1α mRNA and PGC-1α protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1α mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1α expression during atrophy.

  7. Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1α Expression and Atrophy Markers.

    Science.gov (United States)

    Rahnert, Jill A; Zheng, Bin; Hudson, Matthew B; Woodworth-Hobbs, Myra E; Price, S Russ

    2016-01-01

    Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1α and overexpression of PGC-1α counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2), is a positive modulator of PGC-1α transcription. We previously reported that PGC-1α expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation), suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1α expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h) to induce atrophy. Dex decreased PGC-1α mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA) was decreased whereas SIK was increased. To assess PGC-1α transcription, muscle cells were transfected with a PGC-1α luciferase reporter plasmid (PGC-1α-Luc). Dex suppressed PGC-1α luciferase activity while both isobutylmethylxanthine (IBMX) and over-expression of CRTC1 or CRTC2 increased PGC-1α-Luc activity. Mutation of the CRE binding site from PGC-1α-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1α mRNA and PGC-1α protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1α mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1α expression during atrophy.

  8. Neuroendocrine Cancer of Rectum Metastasizing to Ovary

    Science.gov (United States)

    Amin, Sapna Vinit; Kumaran, Aswathy; Bharatnur, Sunanda; Vasudeva, Akhila; Udupa, Kartik; Venkateshiah, Dinesh Bangalore; Bhat, Shaila T.

    2016-01-01

    Neuroendocrine carcinomas (NECs) are rare malignancies that originate from the hormone-producing cells of the body's neuroendocrine system. Rectal high grade NEC (HG-NEC) constituting less than 1% of colorectal cancers can cause large ovarian metastasis that may be the initial presenting complaint. Ovarian Krukenberg tumor from a primary rectal HG-NEC is a very unusual and exceedingly uncommon differential diagnosis for secondary ovarian malignancy. This case report describes one such extremely rare case of a woman who had presented to the gynecology department with features suggestive of ovarian malignancy and was ultimately diagnosed to have Krukenberg tumor originating from neuroendocrine cancer of rectum. We felt this is a good opportunity to spread more light on neuroendocrine neoplasms that are very rare in gynecological practice. PMID:27293931

  9. Maternal undernutrition does not alter Sertoli cell numbers or the expression of key developmental markers in the mid-gestation ovine fetal testis

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    Andrade Luis P

    2013-01-01

    Full Text Available Abstract Background The aim of this study was to determine the effects of maternal undernutrition on ovine fetal testis morphology and expression of relevant histological indicators. Maternal undernutrition, in sheep, has been reported, previously, to alter fetal ovary development, as indicated by delayed folliculogenesis and the altered expression of ovarian apoptosis-regulating gene products, at day 110 of gestation. It is not known whether or not maternal undernutrition alters the same gene products in the day 110 fetal testis. Design and methods Mature Scottish Blackface ewes were fed either 100% (Control; C or 50% (low; L of estimated metabolisable energy requirements of a pregnant ewe, from mating to day 110 of gestation. All pregnant ewes were euthanized at day 110 and a sub-set of male fetuses was randomly selected (6 C and 9 L for histology studies designed to address the effect of nutritional state on several indices of testis development. Sertoli cell numbers were measured using a stereological method and Ki67 (cell proliferation index, Bax (pro-apoptosis, Mcl-1 (anti-apoptosis, SCF and c-kit ligand (development and apoptosis gene expression was measured in Bouins-fixed fetal testis using immunohistochemistry. Results No significant differences were observed in numbers of Sertoli cells or testicular Ki67 positive cells. The latter were localised to the testicular cords and interstitium. Bax and Mcl-1 were localised specifically to the germ cells whereas c-kit was localised to both the cords and interstitium. SCF staining was very sparse. No treatment effects were observed for any of the markers examined. Conclusions These data suggest that, unlike in the fetal ovary, maternal undernutrition for the first 110 days of gestation affects neither the morphology of the fetal testis nor the expression of gene products which regulate apoptosis. It is postulated that the effects of fetal undernutrition on testis function may be expressed

  10. Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis.

    Science.gov (United States)

    Zhang, K E; Ge, Shu-Jian; Lin, Xiao-Yan; Lv, Bei-Bei; Cao, Zhi-Xin; Li, Jia-Mei; Xu, Jia-Wen; Wang, Qiang-Xiu

    2016-03-01

    Intercellular adhesion molecule 1 (ICAM-1) is important in the progression of inflammatory responses. Recently, increased levels of ICAM-1 have been reported in a number of types of malignancy. The present study aimed to investigate ICAM-1 expression in papillary thyroid cancer (PTC) and in Hashimoto's thyroiditis (HT) with PTC-like nuclear alterations, and to assess the predictive value of ICAM-1 in thyroid lesions. ICAM-1 expression was retrospectively investigated in 132 consecutive cases of PTC, 72 cases of HT, 10 of follicular cancer, 15 of follicular adenoma, 16 of nodular goiter and 8 samples of normal thyroid tissue using immunohistochemical analyses, and in 42 PTC patients using western blotting. ICAM-1 expression was not detected in normal follicular cells, follicular lesions (adenoma and cancer) and benign nodular hyperplasia, but was frequently overexpressed in PTC cells. ICAM-1 overexpression was associated with extra-thyroidal invasion and lymph node metastasis; no association was found with age, gender, tumor size, multifocality, pathological stage, recurrence or distant metastasis. ICAM-1 expression in HT patients with PTC-like nuclear alterations was significantly higher than that in HT cases with non-PTC-like features. Compared with antibodies against cytokeratin 19, galectin-3 and Hector Battifora mesothelial-1, ICAM-1 was the most sensitive marker for the detection of PTC-like features in HT. These findings demonstrate that ICAM-1 expression is upregulated in PTC and in HT with PTC-like nuclear alterations. This feature may be an important factor in the progression of cancer of the thyroid gland.

  11. 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 and extrapol...... and extrapolation of data obtained from more common types of neuroendocrine tumours. This review reflects our view of the current state of the art of diagnosis and treatment of patients with BP-NET....

  12. Pathologic research update of colorectal neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.

  13. Design and Validation of the GI-NEC Score to Prognosticate Overall Survival in Patients With High-Grade Gastrointestinal Neuroendocrine Carcinomas

    OpenAIRE

    Valle, Juan; Lamarca, Angela; McNamara, Mairead; Hubner, Richard; Barriuso, Jorge

    2017-01-01

    BACKGROUND: Prognostic markers for risk stratification of patients with gastrointestinal high-grade neuroendocrine carcinomas (GI-NECs) are lacking; we designed and validated a prognostic score for overall survival (OS). METHODS: Consecutive patients diagnosed in five neuroendocrine specialist European centers were included. Patients were divided into three cohorts: a training cohort (TC), an external validation cohort (EVC), and a prospective validation cohort (PVC). Prognostic factors were ...

  14. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

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

    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...

  15. [Activation of the neuroendocrine system during changes in homeostasis during stress conditions].

    Science.gov (United States)

    Vigas, M; Jezová, D

    1996-02-01

    Neuroendocrine response to stress stimuli is aimed to maintain body homeostasis. The activation of the neuroendocrine system is accomplished mainly by two ways: by feedback regulation based on the recognition of altered metabolic homeostasis by appropriate receptors sending the signal into the CNS, and by forward regulation involving a direct stimulation of the neuroendocrine system by a central command coming from an activated brain regulatory center. With regard to mechanisms of neuroendocrine activation, the signal specificity and site of its origin are of particular importance. The significance of the signal in neuroendocrine responses has been evaluated in three different stress conditions: hypoglycemia, surgical trauma and dynamic physical exercise. The stimulus inducing neuroendocrine response during hypoglycemia is the glucopenia. The signal for the activation of the neuroendocrine response is generated in glucosensitive cells which are not located in a single brain structure (hypothetical glucostat). The signal for growth hormone, vasopressin and oxytocin release is produced in brain structures protected by the blood-brain barrier, that for ACTH release in regions both protected and unprotected by the barrier, while the signal for prolactin release is generated in tissues lacking the blood-brain barrier. The neuroendocrine response during surgical trauma is activated by a signal formed in the damaged tissue reaching the CNS by neural pathways. Moreover, cytokins may participate on endocrine stimulation in those surgical interventions in which a large amount of bacterial endotoxins is released. During a complicated surgery, e.g. during a bypass other signals and modifying factors, such as hypothermia, dilution of blood, hypoperfusion of organs, rewarming of the body and hormone degradation in the oxygenator are important. On the On the other hand, during a short-term dynamic exercise, a forward regulation by a central signal from the activated CNS motor

  16. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3)

    DEFF Research Database (Denmark)

    Sorbye, H; Welin, S; Langer, S W;

    2013-01-01

    Background As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Patients and methods Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively...

  17. Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms

    NARCIS (Netherlands)

    Wymenga, ANM; Eriksson, B; Salmela, PI; Jacobsen, MB; Van Cutsem, EJDG; Fiasse, RH; Valimaki, MJ; Renstrup, J; de Vries, EGE; Oberg, KE

    Purpose: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL), Patients and Methods:

  18. Notch signaling modulates hypoxia-induced neuroendocrine differentiation of human prostate cancer cells.

    Science.gov (United States)

    Danza, Giovanna; Di Serio, Claudia; Rosati, Fabiana; Lonetto, Giuseppe; Sturli, Niccolò; Kacer, Doreen; Pennella, Antonio; Ventimiglia, Giuseppina; Barucci, Riccardo; Piscazzi, Annamaria; Prudovsky, Igor; Landriscina, Matteo; Marchionni, Niccolò; Tarantini, Francesca

    2012-02-01

    Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro. Exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch-mediated signaling, as shown by reduced levels of the Notch target genes, Hes1 and Hey1. NED was promoted by attenuation of Hes1 transcription, as cells expressing a dominant-negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia downregulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen-independent cell lines, PC-3 and Du145, it did not change the extent of NED in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Hypoxia induces NED of LNCaP cells in vitro, which seems to be driven by the inhibition of Notch signaling with subsequent downregulation of Hes1 transcription. ©2011 AACR.

  19. NEUROENDOCRINE DISTURBANCES FOLLOWING HEAD INJURIES

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    Vinayak

    2015-05-01

    Full Text Available INTRODUCTION: Traumatic brain injury (TBI is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long - term cognitive, behavioural, psychological and social defects. Recently, c linical evidence has demonstrated that TBI may frequently cause hypothalamic – pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. CASE REPORT: 32 year s old female presented with a history of fall from two wheeler on back hitting the head on occipital region with no history of vomiting, loss of consciousness, ENT bleed. Her GCS was 15/15. Patient was asymptomatic and was discharged from hospital on fifth day. Seven days after discharge patient again presented with heavine ss in her both breasts associated with pain and whitish discharge from both the nipples and mild fever since last two days. CONCLUSION: TBI is a public health problem that requires more effective strategies to improve the outcome and minimize disability of the affected patients. Changes in pituitary hormone secretion may be observed during the acute phase post - TBI, representing part of the acute adaptive response to the injury. Neuroendocrine disturbances, caused by damage to the pituitary and/or hypothalam us, is a frequent complication of TBI and may occur at any time after the acute event. Pituitary dysfunction presents more frequently as an isolated, and more rarely as a complete, deficiency.

  20. The limited screening value of insulin-like growth factor-i as a marker for alterations in body composition in very long-term adult survivors of childhood cancer

    NARCIS (Netherlands)

    K. Blijdorp (Karin); M.M. van den Heuvel-Eibrink (Marry); R. Pieters (Rob); A.M. Boot (Annemieke); J.P. Sluimer (Johanna); A. van der Lelij (Allegonda); S.J.C.M.M. Neggers (Bas)

    2012-01-01

    textabstractBackground: The clinical relevance of low IGF-I levels, caused by cranial radiotherapy, in adult childhood cancer survivors has not been studied extensively. We evaluated whether IGF-I is a useful marker for altered body composition and growth hormone deficiency (GHD) in this group. Proc

  1. The limited screening value of insulin-like growth factor-i as a marker for alterations in body composition in very long-term adult survivors of childhood cancer

    NARCIS (Netherlands)

    Blijdorp, Karin; van den Heuvel-Eibrink, Marry; Pieters, Rob; Boot, Annemieke; Sluimer, Johanna; van der Lelij, Aart-Jan; Neggers, Sebastian

    2012-01-01

    Background The clinical relevance of low IGF-I levels, caused by cranial radiotherapy, in adult childhood cancer survivors has not been studied extensively. We evaluated whether IGF-I is a useful marker for altered body composition and growth hormone deficiency (GHD) in this group. Procedure We

  2. Expression of papillary thyroid carcinoma-associated molecular markers and their significance in follicular epithelial dysplasia with papillary thyroid carcinoma-like nuclear alterations in Hashimoto's thyroiditis.

    Science.gov (United States)

    Ma, Heng; Yan, Jin; Zhang, Chao; Qin, Shenghui; Qin, Lingzhi; Liu, Liwei; Wang, Xi; Li, Naping

    2014-01-01

    The aim of this study was to evaluate the expression of papillary thyroid carcinoma (PTC)-associated tumor markers in follicular epithelial dysplasia showing PTC-like nuclear alterations (FED) in Hashimoto's thyroiditis (HT) and to explore the relationship between HT and PTC. In this study, 43 PTC, 18 HT with FED and 16 peritumoral benign thyroid tissues were immunohistochemically analyzed for CK19, galectin-3, HBME-1, CD56, claudin-1 and NGAL expression. Our research revealed that in HT, the expression of CK19, galectin-3, HBME-1, claudin-1 and NGAL was focal and limited to FED, while CD56 was strongly positive in FED and most Hürthle cells. The stain intensity of CK19, claudin-1 and NGAL in FED decreased compared with PTC, but were significantly higher than that in peritumoral benign thyroid tissues (all P 0.05). In conclusion, In HT, FED might be a precancerous condition closely associated with PTC development as they have overlaps in cytological and immunomarker profiles, indicating that in patients with HT, under prolonged stimuli from chronic inflammation, part of follicular epithelia may show regeneration, hyperplasia, Hürthle cell metaplasia and dysplasia, eventually malignant transformation. Hence, long term follow-up and regular inspection would be necessary for Hashimoto's thyroiditis with FED.

  3. Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells

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    Albertoni Guilherme

    2012-12-01

    Full Text Available Abstract Background Chronic hepatitis C (CHC has emerged as a leading cause of cirrhosis in the U.S. and across the world. To understand the role of apoptotic pathways in hepatitis C virus (HCV infection, we studied the mRNA and protein expression patterns of apoptosis-related genes in peripheral blood mononuclear cells (PBMC obtained from patients with HCV infection. Methods The present study included 50 subjects which plasma samples were positive for HCV, but negative for human immunodeficiency virus (HIV or hepatitis B virus (HBV. These cases were divided into four groups according to METAVIR, a score-based analysis which helps to interpret a liver biopsy according to the degree of inflammation and fibrosis. mRNA expression of the studied genes were analyzed by reverse transcription of quantitative polymerase chain reaction (RT-qPCR and protein levels, analyzed by ELISA, was also conducted. HCV genotyping was also determined. Results HCV infection increased mRNA expression and protein synthesis of caspase 8 in group 1 by 3 fold and 4 fold, respectively (p group 4 HCV infection increased mRNA expression and protein synthesis of caspase 9 by 2 fold and 1,5 fold, respectively (p group 1 by 4 fold and 5 fold, respectively, and in group 4 by 6 fold and 7 fold, respectively (p Conclusions HCV induces alteration at both genomic and protein levels of apoptosis markers involved with extrinsic and intrinsic pathways.

  4. Acute Pancreatitis Secondary to Pancreatic Neuroendocrine Tumours

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    Grinó P

    2003-03-01

    Full Text Available CONTEXT: Pancreatic neoplasms are an uncommon aetiology of acute pancreatitis. Pancreatic neuroendocrine tumours are a rare subgroup of pancreatic neoplasms. CASE REPORT: We report on three patients having acute pancreatitis secondary to pancreatic neuroendocrine tumours, one of them with severe pancreatitis, and review the published cases up to now. Only 22 patients with acute pancreatitis secondary to pancreatic neuroendocrine tumours have been reported (including the present cases. Most of these cases were of non-functioning neoplasms and the course of the pancreatitis tended to be mild. In the most recent reports and in the present cases, the initial diagnostic method was CT scan. Less than half had metastases when the tumour was diagnosed and mortality from these neoplasms reached approximately 50%. CONCLUSIONS: Pancreatic neuroendocrine tumours can cause acute pancreatitis even in patients under 50 years of age. On many occasions, the tumours are non-functioning; therefore, acute pancreatitis may be the first clinical symptom. Consequently, faced with acute pancreatitis of unknown origin, a non-functioning neuroendocrine tumour should be ruled out.

  5. Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

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    Menon Santosh

    2010-01-01

    Full Text Available Primary sinonasal tumors with neuroendocrine differentiation (SCND are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC, sinonasal neuroendocrine carcinoma (SNEC, esthesioneuroblastoma (ENB and small cell carcinoma (SmCC. The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute′s pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With

  6. Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma

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    Uchiyama Chieko

    2012-06-01

    Full Text Available Abstract Background Gastric neuroendocrine carcinoma (G-NEC is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease. Methods Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes. Results The mean patient age was 73 years (range 63 to 86 years. There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers. Conclusions Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer. Mini abstract G-NEC grows rapidly and metastasizes to the lymph nodes, retaining its pathological and immunohistochemical heterogeneity even at the metastatic sites.

  7. 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)

  8. Impact of Prenatal Stress on Neuroendocrine Programming

    Directory of Open Access Journals (Sweden)

    Odile Viltart

    2007-01-01

    Full Text Available Since life emerged on the Earth, the development of efficient strategies to cope with sudden and/or permanent changes of the environment has been virtually the unique goal pursued by every organism in order to ensure its survival and thus perpetuate the species. In this view, evolution has selected tightly regulated processes aimed at maintaining stability among internal parameters despite external changes, a process termed homeostasis. Such an internal equilibrium relies quite heavily on three interrelated physiological systems: the nervous, immune, and endocrine systems, which function as a permanently activated watching network, communicating by the mean of specialized molecules: neurotransmitters, cytokines, and hormones or neurohormones. Potential threats to homeostasis might occur as early as during in utero life, potentially leaving a lasting mark on the developing organism. Indeed, environmental factors exert early-life influences on the structural and functional development of individuals, giving rise to changes that can persist throughout life. This organizational phenomenon, encompassing prenatal environmental events, altered fetal growth, and development of long-term pathophysiology, has been named early-life programming. Over the past decade, increased scientific activities have been devoted to deciphering the obvious link between states of maternal stress and the behavioral, cognitive, emotional, and physiological reactivity of the progeny. This growing interest has been driven by the discovery of a tight relationship between prenatal stress and development of short- and long-term health disorders. Among factors susceptible of contributing to such a deleterious programming, nutrients and hormones, especially steroid hormones, are considered as powerful mediators of the fetal organization since they readily cross the placental barrier. In particular, variations in circulating maternal glucocorticoids are known to impact this

  9. Neuroendocrine aspects of Tourette syndrome.

    Science.gov (United States)

    Martino, Davide; Macerollo, Antonella; Leckman, James F

    2013-01-01

    There is sparse evidence suggesting the participation of neuroendocrine mechanisms, mainly involving sex and stress steroid hormones, to the pathophysiology of neurodevelopmental disorders such as Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). Patients with TS exhibit a sex-specific variability in gender distribution (male/female ratio=3-4/1) and in its natural history, with a severity peak in the period around puberty. The administration of exogenous androgens may worsen tics in males with TS, whereas drugs counteracting the action of testosterone might show some antitic efficacy. This suggests a higher susceptibility of patients with TS to androgen steroids. There are insufficient data on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in TS. However, preliminary evidence suggests that a subgroup of women with TS might be more sensitive to the premenstrual trough of estrogen levels. Patients with TS exhibit differences in a number of behavioral, cognitive, and anatomical traits that appear to be sex related. There is a body of evidence supporting, albeit indirectly, the hypothesis of an increased exposure to androgenic steroids during the very early phases of neural development. Animal models in rodents suggest a complex role of gonadal hormones upon the modulation of anxiety-related and stereotyped behaviors during adult life. Patients with TS exhibit an enhanced reactivity of the hypothalamic-pituitary-adrenal axis to external stressors, despite a preserved diurnal cortisol rhythm and a normal restoration of the baseline activity of the axis following the acute stress response. Preliminary evidence suggests the possible implication of oxytocin (OT) in disorders related to the TS spectrum, especially non-tic-related OCD. The injection of OT in the amygdala of rodents was shown to be able to induce hypergrooming, suggesting the possible involvement of this neuropeptide in the pathophysiology of complex, stereotyped behaviors. In

  10. [Pulmonary neuroendocrine tumors and preneoplasic lesions].

    Science.gov (United States)

    Rouquette Lassalle, Isabelle

    2016-01-01

    In the recently published 2015 World Health Organization (WHO) classification of tumors of the lungs, all neuroendocrine tumors of the lungs are presented for the first time in one single chapter. In this classification, high-grade small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are differentiated from intermediate grade atypical carcinoids (AC) and low-grade typical carcinoids as well as from preinvasive lesion diffuse neuroendocrine hyperplasia DIPNECH. In the 2004 WHO classification, SCLC and carcinoids each had a separate chapter and LCNEC was listed in the chapter on large cell carcinoma of the lungs. The new WHO classification also gives some recommendations for the diagnosis on small biopsies. This review describes morphological, immunohistochemical, and genomic characteristic of these tumors according to the new classification.

  11. 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

  12. Large Cell Neuroendocrine Carcinoma of the Lung

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    Yusuf Aydemir

    2015-11-01

    Full Text Available Large-cell neuroendocrine carcinomas of the lung are extremely rare. There are difficulties related to the diagnosis and treatment and there are no consensus because of the small number of studies. 65-year-old male patient presented with hemoptysis. Chest X-ray and thoracic computorized tomography scan showed a mass lesion and it could not be diagnosed by bronchoscopic biopsy and lavage. Lobectomy was performed due to the high value of standardized uptake value in positron emission tomography. Large cell neuroendocrine carcinoma was diagnosed with pathological evaluation and immunohistochemical study and after 20-month follow-up there was no recurrence. The diagnosis, treatment, and prognosis of large cell neuroendocrine carcinoma in the light of the literature is presented.

  13. Post-exercise cold water immersion does not alter high intensity interval training-induced exercise performance and Hsp72 responses, but enhances mitochondrial markers.

    Science.gov (United States)

    Aguiar, Paula Fernandes; Magalhães, Sílvia Mourão; Fonseca, Ivana Alice Teixeira; da Costa Santos, Vanessa Batista; de Matos, Mariana Aguiar; Peixoto, Marco Fabrício Dias; Nakamura, Fábio Yuzo; Crandall, Craig; Araújo, Hygor Nunes; Silveira, Leonardo Reis; Rocha-Vieira, Etel; de Castro Magalhães, Flávio; Amorim, Fabiano Trigueiro

    2016-09-01

    it was not affected by CWI (p = 0.99). Cold water immersion does not alter HIIT-induced Hsp72, AMPK, p38 MAPK, and exercise performance but was able to increase some markers of cellular stress response and signaling molecules related to mitochondria biogenesis.

  14. Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

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    Fabio Lanfranco

    2010-01-01

    Full Text Available Obstructive sleep apnea syndrome (OSAS is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH secretion coupled to reduced insulin-like growth factor-I (IGF-I concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death.

  15. Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in rat model of ischemic-hypoxic brain injury

    Institute of Scientific and Technical Information of China (English)

    Liping Zhang; Liping Zou

    2008-01-01

    BACKGROUND: Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function, and these positive effects might be due to neural plasticity. OBJECTIVE: Myelin basic protein (MBP), microtubule-associated protein 2 (MAP2), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) were selected as markers of neural remodeling, and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment. DESIGN, TIME AND SETTING: A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007. MATERIALS: Twenty-four Sprague Dawley rat pups, aged 7 days, were selected for the present experiment. The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS: All animals were randomly divided into three groups: sham operation, model, and electro-acupuncture treatment, with 8 rats in each group. Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury. Upon model established, rats underwent hypobaric oxygen intervention for 24 hours. Only the left common carotid artery was exposed in rats of the sham operation group, without model establishment or oxygen intervention. The rats in the electro-acupuncture treatment group were treated with electro-acupuncture. One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint. The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second, as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second. Maximal current through the two dectrodes was limited to 3-5 mA. The stimulation lasted for 30 minutes per day for 2 weeks. Rats in the sham operation and model groups were not treated

  16. Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition.

    Science.gov (United States)

    Díaz-Rúa, Rubén; Keijer, Jaap; Caimari, Antoni; van Schothorst, Evert M; Palou, Andreu; Oliver, Paula

    2015-04-01

    Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.

    Science.gov (United States)

    Wang, Sheng-Chun; Lin, Xiao-Lin; Wang, Hui-Yan; Qin, Yu-Juan; Chen, Lin; Li, Jing; Jia, Jun-Shuang; Shen, Hong-Fen; Yang, Sheng; Xie, Rao-Ying; Wei, Fang; Gao, Fei; Rong, Xiao-Xiang; Yang, Jie; Zhao, Wen-Tao; Zhang, Ting-Ting; Shi, Jun-Wen; Yao, Kai-Tai; Luo, Wei-Ren; Sun, Yan; Xiao, Dong

    2015-11-03

    Overexpression of the transcriptional factor Hes1 (hairy and enhancer of split-1) has been observed in numerous cancers, but the precise roles of Hes1 in epithelial-mesenchymal transition (EMT), cancer invasion and metastasis remain unknown. Our current study firstly revealed that Hes1 upregulation in a cohort of human nasopharyngeal carcinoma (NPC) biopsies is significantly associated with the EMT, invasive and metastatic phenotypes of cancer. In the present study, we found that Hes1 overexpression triggered EMT-like cellular marker alterations of NPC cells, whereas knockdown of Hes1 through shRNA reversed the EMT-like phenotypes, as strongly supported by Hes1-mediated EMT in NPC clinical specimens described above. Gain-of-function and loss-of-function experiments demonstrated that Hes1 promoted the migration and invasion of NPC cells in vitro. In addition, exogenous expression of Hes1 significantly enhanced the metastatic ability of NPC cells in vivo. Chromatin immunoprecipitation (ChIP) assays showed that Hes1 inhibited PTEN expression in NPC cells through binding to PTEN promoter region. Increased Hes1 expression and decreased PTEN expression were also observed in a cohort of NPC biopsies. Additional studies demonstrated that Hes1-induced EMT-like molecular changes and increased motility and invasion of NPC cells were mediated by PTEN. Taken together, our results suggest, for what we believe is the first time, that Hes1 plays an important role in the invasion and metastasis of NPC through inhibiting PTEN expression to trigger EMT-like phenotypes.

  18. 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.

  19. Concepts of neuroendocrine cardiology and neuroendocrine immunology, chemistry and biology of signal molecules.

    Science.gov (United States)

    Galoyan, Armen

    2010-12-01

    Discovery of neurosecretion of cardioactive neurohormones produced by hypothalamic nuclei (NSO and NPV), as well as the biosynthesis of several immunomodulators (signal molecules of the neuroendocrine immune system of brain), deciphering of their chemical structure and study of their biological properties led to the foundation of two important trends of neurobiology: neuroendocrine immunology and cardiology. Hormone formation by atrium ganglionary nerve cells and auriculum establishment of neurohumoral interactions between hypothalamic and atrium neurosecretion indicated the existence of the system neuroendocrine hypothalamus--endocrine heart. Study of their biological properties promoted creation of powerful neurohormonal preparations for the treatment of immune, cardio-vascular, neurodegenerative, infectious and tumor diseases. Concepts suggested by us on neuroendocrine cardiology and immunology, create large perspectives for development of the theory and its implementation in medicine.

  20. C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

    Science.gov (United States)

    Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery.

  1. Role of neuropeptide FF in central cardiovascular and neuroendocrine regulation.

    Science.gov (United States)

    Jhamandas, Jack H; Goncharuk, Valeri

    2013-01-01

    Neuropeptide FF (NPFF) is an octapeptide belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain including central cardiovascular and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat and human brain. Herein, we review evidence for the role of NPFF in central regulation of blood pressure particularly within the brainstem and the hypothalamic paraventricular nucleus (PVN). At a cellular level, NPFF demonstrates distinct responses in magnocellular and parvocellular neurons of the PVN, which regulate the secretion of neurohypophyseal hormones and sympathetic outflow, respectively. Finally, the presence of NPFF system in the human brain and its alterations within the hypertensive brain are discussed.

  2. Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

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    Anna M. M. Daubenbüchel

    2015-03-01

    Full Text Available Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement, a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92% but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007. Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

  3. Clinical experience in appendiceal neuroendocrine neoplasms

    Science.gov (United States)

    Ozcelik, Caglar K.; Bozdogan, Nazan; Dibekoglu, Cengiz

    2015-01-01

    Aim of the study To analyse the incidence of appendiceal neuroendocrine neoplasms in appendectomy specimens and establish the epidemiological and histopathological features, treatment, and clinical course. Material and methods Between 2004 and 2013, 975 patients who underwent appendectomy in Ankara Oncology Education and Research Hospital were retrospectively analysed. Results Neuroendocrine neoplasm was detected in the nine of 975 (0.9%) patients. Neuroendocrine neoplasms were diagnosed in eight patients by appendectomy, which was performed because of the prediagnosis of acute appendicitis, and in one patient by the suspicious mass detection during surgical procedures that were done in the appendix for a different reason. Eight of the patients’ tumours were in the tip of the appendix, and one of the patients’ tumours was at the base of appendix. Tumour size in 77.8% of patients was equal or less than 1 cm, in 22.2% patients it was 1–2 cm. There was tumour invasion in the muscularis propria layer in four patients, in the serosa layer in three patients, and in the deep mesoappendix in two patients. Patients were followed for a median of 78 months. In the follow-up of patients who were operated because of colon cancer, metachronous colon tumour evolved. This patient died due to progressive disease. Other patients are still disease-free. Conclusions The diagnosis of neuroendocrine neoplasm is often incidentally done after appendectomy. Tumour size is important in determining the extent of disease and in the selection of the surgical method during operation. PMID:26793027

  4. 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.

  5. Peptide receptor therapies in neuroendocrine tumors

    NARCIS (Netherlands)

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

    2009-01-01

    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 cruci

  6. Surgical management of pancreatic neuroendocrine tumors

    NARCIS (Netherlands)

    Jilesen, A.P.J.

    2015-01-01

    This thesis gives an overview of the surgical management and prognosis of patients with pancreatic neuroendocrine tumors (pNET). A systematic review including 2600 studies, was performed on complications and survival after different surgical procedures for pNETs. The overall pancreatic fistula rate

  7. Review of recent advances in medical treatment for neuroendocrine neoplasms:somatostatin analogs and chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Francesca Spada; Monica Valente

    2016-01-01

    Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours often producing high levels of hormones and causing symptoms. There are a number of different types of NENs. They usually arise as advanced and low/intermediate grade only in a minority of cases, as high grade. Treatment depends on which type and may include surgery, interventional radiology, and systemic treatment, including chemotherapy, somatostatin analogs, interferon α2b, peptide receptor radionuclide therapy, and only for pancreatic neuroendocrine tumors, molecular targeted agents, including everolimus and sunitinib. The aim of the article is to review the medical approaches with somatostatin analogs and chemotherapy. The treatment of NENs is mainly based on their biological characteristics of aggressiveness and functional features, such as symptoms and endocrine markers.

  8. Neuroendocrine diffuse system of the respiratory tract of Rana temporaria: an immunocytochemical study.

    Science.gov (United States)

    Bodegas, M E; Montuenga, L M; Sesma, P

    1995-11-01

    The neuroendocrine cell population of the respiratory system of Rana temporaria has been studied by means of immunocytochemical methods at the light-microscopic level. Isolated or clustered endocrine cells have been found in the epithelium of the buccal cavity, glottis, larynx, and lung. Nine different types of endocrine isolated cell types can be distinguished according to their immunoreactivity to several regulatory peptides [calcitonin, substance P, bombesin, peptide histidine isoleucine (PHI), cholecystokinin (CCK), and endothelin 1] and neuroendocrine markers (7B2, chromogranin, and serotonin). Neuroepithelial bodies are innervated clusters of cells simultaneously immunoreactive for serotonin and 7B2. Nerves and/or neurons have been detected in different regions of the respiratory system using antibodies against protein gene product 9.5, serotonin, calcitonin gene-related peptide (CGRP), substance P, PHI, helodermin, and CCK.

  9. Mixed exocrine-neuroendocrine carcinoma of the nasal cavity: clinico-pathologic and molecular study of a case and review of the literature.

    Science.gov (United States)

    La Rosa, Stefano; Furlan, Daniela; Franzi, Francesca; Battaglia, Paolo; Frattini, Milo; Zanellato, Elena; Marando, Alessandro; Sahnane, Nora; Turri-Zanoni, Mario; Castelnuovo, Paolo; Capella, Carlo

    2013-03-01

    Sinonasal intestinal-type adenocarcinomas (ITACs) are rare neoplasms histologically resembling intestinal adenocarcinomas. Although a neuroendocrine differentiation in ITACs has been described, true mixed exocrine-neuroendocrine carcinomas, neoplasms in which each component represents at least 30 % of the lesion, are extremely rare and their molecular alterations are largely unknown. We describe herein the clinico-pathologic features, the methylation profile, chromosomal gains and losses, and mutation analysis of KRAS, BRAF and p53 in a nasal mixed exocrine-neuroendocrine carcinoma resected in a 79-year-old man. The tumor was composed of an ITAC and a poorly differentiated neuroendocrine carcinoma. Both exocrine and neuroendocrine components were CK8, CK20, CDX2 and p53 positive, and CK7 and TTF1 negative. The neuroendocrine component also showed immunoreactivity for chromogranin A, synaptophysin, serotonin and glicentin. Gains and losses were found at following chromosome regions: 17p13 (TP53), 14q24 (MLH3), 19q13 (KLK3), 5q21 (APC), 7q21 (CDK6), 9q34 (DAPK1), 12p13 (TNFRSF 1A, CDKN1B), 13q12 (BRCA2), 17p13.3 (HIC1), 18q21 (BCL2), and 22q12 (TIMP3). Aberrant methylation was detected only in the neuroendocrine component and involved APC and DAPK1 genes. No mutation of KRAS (exons 2-4), BRAF (exon 15), and p53 (exons 4-10) was found in both components. The results suggest a monoclonal origin of the tumor from a pluripotent cell undergoing a biphenotypic differentiation and that the neuroendocrine differentiation may be from an exocrine to an endocrine pathway. We have also reviewed the literature on sinonasal mixed exocrine-neuroendocrine carcinomas to give to the reader a comprehensive overview of these very rare tumor types.

  10. A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

    Science.gov (United States)

    Palamiuc, Lavinia; Noble, Tallie; Witham, Emily; Ratanpal, Harkaranveer; Vaughan, Megan; Srinivasan, Supriya

    2017-01-01

    Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity. PMID:28128367

  11. Neuroendocrine tumor of the pancreas in a patient with tuberous sclerosis: a case report and review of the literature.

    Science.gov (United States)

    Díaz Díaz, Delissa; Ibarrola, Carolina; Goméz Sanz, Ramón; Pérez Hurtado, Bladimir; Salazar Tabares, Johny; Colina Ruizdelgado, Francisco

    2012-08-01

    A rare case of pancreatic neuroendocrine neoplasm in a patient with tuberous sclerosis complex is described. The patient was a 31-year-old man who had multiple congenital subependymal nodules, bilateral cortical tubers, and seizures of difficult control. A 2.3 cm × 2 cm well-delimitated solid tumor in the tail of the pancreas was discovered during a monitoring abdominal computed tomography. A distal pancreatectomy was performed. Histologically, the tumor was formed by uniform cells with moderated cytoplasm arranged in a combined trabecular and nested pattern. The nuclear features were bland, and mitosis was infrequent. There was no vascular invasion. Immunoreactivity for cytokeratine AE1/AE3, chromogranin A, and synaptophysin confirmed the neuroendocrine nature of this neoplasia. Pancreatic hormones were negatives. One of the 5 lymph nodes isolated from the peripancreatic adipose tissue was positive for metastases. Small series and case reports have documented that in tuberous sclerosis many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid, and other neuroendocrine tissue, including islet cells of the pancreas. However, the true association of these pathological conditions remains uncertain. As far as we know, there are 10 cases reported of pancreatic neuroendocrine tumors in a setting of tuberous sclerosis complex, in which 2 cases resulted in malignant, nonfunctioning pancreatic neuroendocrine tumors.

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

    Directory of Open Access Journals (Sweden)

    Vincent eGeenen

    2013-10-01

    Full Text Available 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

  13. 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.

  14. [Is the immune system our sixth sense? Relation between the immune and neuroendocrine systems].

    Science.gov (United States)

    Ferencík, M; Stvrtinová, V

    1997-04-01

    There is an overwhelming evidence that cytokines, peptide hormones and neurotransmitters, as well as their receptors, are present in the brain, endocrine and immune systems. The structure and pattern of synthesis of these peptides by leukocytes appear similar to those synthesized in the neuroendocrine system, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators inside of the each system and also in bidirectional communication between the immune and neuroendocrine systems. Such communication suggest an immunoregulatory role for the brain and a sensory function for the immune system which may sense stimuli that are not recognized by the central and peripheral nervous systems (noncognitive stimuli). The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to deposit the hormone locally at the target site. Several immunoregulatory cytokines, including IL-1, IL-2, IL-6, IFN-gama and TNF are produced not only in the immune system but in the neuroendocrine system as well. They have profound effects on neuroendocrine functions especially on hypothalamic pituitary axes. Neuroendocrine influences that modulate the immune function mainly include mental and physical stress. It can reduce the resistance of organism to infectious diseases and malignancies by compromising the immune system directly or indirectly. The brain is not an immunologically privileged site and therefore may become the target of immunologic attacks resulting in neuroimmunological diseases with an autoimmune component. The impact of psychological and psychosocial factors on the immune system is studied by psychoneuroimmunology whereas neuroendocrine immunology is generally interested in the interactions between the immune and neuroendocrine systems under physiological and pathological conditions. The

  15. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Todorović-Tirnanić Mila

    2015-01-01

    Full Text Available 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 (131I/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 specificity (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/CT methods for

  16. [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

  17. Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp

    2011-01-01

    Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

  18. Neuroprotection via Reduction in Stress: Altered Menstrual Patterns as a Marker for Stress and Implications for Long-Term Neurologic Health in Women

    Science.gov (United States)

    Prokai, David; Berga, Sarah L.

    2016-01-01

    Individuals under chronic psychological stress can be difficult to identify clinically. There is often no outwardly visible phenotype. Chronic stress of sufficient magnitude not only impacts reproductive function, but also concomitantly elicits a constellation of neuroendocrine changes that may accelerate aging in general and brain aging in particular. Functional hypothalamic amenorrhea, a phenotypically recognizable form of stress, is due to stress-induced suppression of endogenous gonadotropin-releasing hormone secretion. Reversal of functional hypothalamic amenorrhea includes restoration of ovulatory ovarian function and fertility and amelioration of hypercortisolism and hypothyroidism. Taken together, recovery from functional hypothalamic amenorrhea putatively offers neuroprotection and ameliorates stress-induced premature brain aging and possibly syndromic Alzheimer’s disease. Amenorrhea may be viewed as a sentinel indicator of stress. Hypothalamic hypogonadism is less clinically evident in men and the diagnosis is difficult to establish. Whether there are other sex differences in the impact of stress on brain aging remains to be better investigated, but it is likely that both low estradiol from stress-induced anovulation and low testosterone from stress-induced hypogonadism compromise brain health. PMID:27999413

  19. Mixed Acinar-Neuroendocrine Carcinoma of the Pancreas with Neuroendocrine Predominance

    Directory of Open Access Journals (Sweden)

    Onyekachi Henry Ogbonna

    2013-01-01

    Full Text Available Background. Pancreatic tumors are rare and could arise from either the exocrine (ductal and acinar cells or the endocrine (neuroendocrine cells components of the pancreas. In some instances, the occurrence of pancreatic tumors comprising both acinar cells and neuroendocrine cells, with neuroendocrine cells making up more than 30% of the tumor, has been identified. This unique entity has been referred to as mixed acinar-neuroendocrine carcinoma (MANEC. Only about 20 such cases have been reported in the literature. Case Report. We report an interesting case of MANEC with neuroendocrine cell predominance in a woman presenting with epigastric pain secondary to a pancreatic mass with acinar and endocrine differentiation. She underwent surgical resection of the tumor and was offered adjuvant treatment chemotherapy with carboplatin, etoposide, and radiotherapy for positive tumor resection margins. Conclusions. Given the paucity of the cases of MANEC, continuous reporting of these cases when identified should be encouraged to aid oncologists in understanding the disease and help establish standardized management.

  20. Colonic neuroendocrine carcinoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes [King Faisal Specialist Hospital and Research Centre, Department of Radiology, MBC 28, Riyadh (Saudi Arabia); Sathiapalan, Rajeev; Kofide, Amani [King Faisal Specialist Hospital and Research Centre, Department of Paediatric Haematology and Oncology, Riyadh (Saudi Arabia); Tulbah, Asthma Mahmoud Mohamed [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia); Al-Mehaidib, Ali [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia)

    2005-03-01

    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.)

  1. Mathematical modeling of the circadian dynamics of the neuroendocrine-immune network in experimentally induced arthritis.

    Science.gov (United States)

    Rao, R; DuBois, D; Almon, R; Jusko, W J; Androulakis, I P

    2016-08-01

    The circadian dynamics of important neuroendocrine-immune mediators have been implicated in progression of rheumatoid arthritis pathophysiology, both clinically as well as in animal models. We present a mathematical model that describes the circadian interactions between mediators of the hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines. Model predictions demonstrate that chronically elevated cytokine expression results in the development of adrenal insufficiency and circadian variability in paw edema. Notably, our model also predicts that an increase in mean secretion of corticosterone (CST) after the induction of the disease is accompanied by a decrease in the amplitude of the CST oscillation. Furthermore, alterations in the phase of circadian oscillation of both cytokines and HPA axis mediators are observed. Therefore, by incorporating the circadian interactions between the neuroendocrine-immune mediators, our model is able to simulate important features of rheumatoid arthritis pathophysiology.

  2. 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.

  3. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

    OpenAIRE

    Godwin Ofikwu; Mani, Vishnu R.; Ajai Rajabalan; Albert Adu; Leaque Ahmed; Dennis Vega

    2015-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs) which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linea...

  4. Treatment of lung large cell neuroendocrine carcinoma.

    Science.gov (United States)

    Lo Russo, Giuseppe; Pusceddu, Sara; Proto, Claudia; Macerelli, Marianna; Signorelli, Diego; Vitali, Milena; Ganzinelli, Monica; Gallucci, Rosaria; Zilembo, Nicoletta; Platania, Marco; Buzzoni, Roberto; de Braud, Filippo; Garassino, Marina Chiara

    2016-06-01

    Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive, and difficult-to-treat tumor. It is classified as a neuroendocrine subtype of large cell lung carcinoma (LCLC) belonging to the non-small cell lung cancer (NSCLC) group, but it is also included in the neuroendocrine tumor (NET) group. Most of the available data related to its treatment derive from retrospective analyses or small case series. For patients with L-LCNEC, prognosis is generally very poor. In early stages (I-II-III), surgery is recommended but does not seem to be sufficient. Platinum-based adjuvant chemotherapy may be useful while the role of neoadjuvant chemotherapy is still not well defined. In patients with advanced L-LCNEC, the chemotherapy regimens used in SCLC still remain the standard of treatment, but results are not satisfactory. Due to their peculiar clinical and biological features and the lack of literature data, there is an emerging need for a consensus on the best treatment strategy for L-LCNEC and for the identification of new therapeutic options. In this review, we will discuss the key aspects of L-LCNEC management with the aim to clarify the most controversial issues.

  5. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    Science.gov (United States)

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  6. IGF-1 drives chromogranin A secretion via activation of Arf1 in human neuroendocrine tumour cells.

    Science.gov (United States)

    Münzberg, Christin; Höhn, Katharina; Krndija, Denis; Maaß, Ulrike; Bartsch, Detlef K; Slater, Emily P; Oswald, Franz; Walther, Paul; Seufferlein, Thomas; von Wichert, Götz

    2015-05-01

    Hypersecretion is the major symptom of functional neuroendocrine tumours. The mechanisms that contribute to this excessive secretion of hormones are still elusive. A key event in secretion is the exit of secretory products from the Golgi apparatus. ADP-ribosylation factor (Arf) GTPases are known to control vesicle budding and trafficking, and have a leading function in the regulation of formation of secretory granula at the Golgi. Here, we show that Arf1 is the predominant Arf protein family member expressed in the neuroendocrine pancreatic tumour cell lines BON and QGP-1. In BON cells Arf1 colocalizes with Golgi markers as well as chromogranin A, and shows significant basal activity. The inhibition of Arf1 activity or expression significantly impaired secretion of chromogranin A. Furthermore, we show that the insulin-like growth factor 1 (IGF-1), a major regulator of growth and secretion in BON cells, induces Arf1 activity. We found that activation of Arf1 upon IGF-1 receptor stimulation is mediated by MEK/ERK signalling pathway in BON and QGP-1 cells. Moreover, the activity of Arf1 in BON cells is mediated by autocrinely secreted IGF-1, and concomitantly, autocrine IGF1 secretion is maintained by Arf1 activity. In summary, our data indicate an important regulatory role for Arf1 at the Golgi in hypersecretion in neuroendocrine cancer cells.

  7. Large-cell lung carcinoma with basaloid architecture and neuroendocrine differentiation: a new type of combined large-cell neuroendocrine carcinoma.

    Science.gov (United States)

    Morbini, Patrizia; Inghilleri, Simona

    2011-04-01

    One of the main differential diagnostic issues in pulmonary large-cell carcinomas is that involving neuroendocrine (NE) and basaloid histotypes. The differential diagnosis of basaloid versus large-cell NE carcinoma requires immunohistochemical determination of NE markers because of morphological overlap between the 2 entities. The authors report a unique case of lung carcinoma with basaloid architecture and NE immunohistochemical features observed in a 64-year-old male smoker who underwent upper left lobectomy for a neoplastic stenosis of the lobar bronchus. The patient died 14 months after surgery. Histological examination showed multiple peripheral nodules of moderately enlarged neoplastic cells with irregular nuclei, with granular chromatin and frequent nucleoli, and diffuse in situ neoplasia involving bronchi, peribronchial glands, and small airways. Immunohistochemistry documented diffuse expression of CD56 in neoplastic cells and isolated cell groups immunoreactive for basal cell markers. The reported case was considered an as-yet-undescribed tumor showing both basaloid and NE differentiation.

  8. Neuroendocrine adaptations to bariatric surgery.

    Science.gov (United States)

    Dixon, J B; Lambert, E A; Lambert, G W

    2015-12-15

    The global epidemic of obesity and its related disease in combination with robust physiological defence of intentional weight loss generates a pressing need for effective weight loss therapies. Bariatric surgery, which works very effectively at delivering substantial sustained weight loss, has been an enigma with respect to mechanism of action. Naive concepts of restriction and malabsorption do not explain the efficacy of the most commonly used bariatric procedures. This century has seen increased interest in unravelling the mystery of the mechanisms underlying surgery associated weight loss with a focus on integrative gastrointestinal (GI) physiology, gut-brain signalling, and beyond weight loss effects on metabolism. GI interventions, some very minor, can alter GI wall stretch and pressure receptors; a range of GI hormones affecting hunger and satiety; bile acid metabolism and signalling; the characteristics of GI microbiome; portal vein nutrient sensing; and circulating concentrations of amino acids. Understanding the mechanisms involved should present targets for less invasive effective therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Searching for biological markers of personality : are there neuroendocrine markers of anxiety?

    OpenAIRE

    Armario García, Antonio

    2013-01-01

    The existence of stable individual differences in cognitive and emotional capabilities both in animals and humans is well-accepted. The theories of personality assume that such individual differences can be categorized and that the richness of individual differences in humans would be the result of the combination of differences in a few underlying personality factors.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Neuroendocrine carcinomas arising in ulcerative colitis:Coincidences or possible correlations?

    Institute of Scientific and Technical Information of China (English)

    Roberto Grassia; Paolo Bodini; Paolo Dizioli; Teresa Staiano; Elena Iiritano; Guglielmo Bianchi; Federico Buffoli

    2009-01-01

    Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis (UC) and Crohn's disease,but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel.With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group oftumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids (NENs) are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immunohistochemical staining for neuroendocrine markers: a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age (35 years vs 77 years) and disease duration (11 years vs 27 years), and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD,NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial,goblet, Paneth and neuroendocrine cells. It has yetto be established which IBD patients have a higher risk of developing NENs.

  12. High-grade neuroendocrine carcinomas of the lung highly express enhancer of zeste homolog 2, but carcinoids do not.

    Science.gov (United States)

    Findeis-Hosey, Jennifer J; Huang, Jiaoti; Li, Faqian; Yang, Qi; McMahon, Loralee A; Xu, Haodong

    2011-06-01

    and as a diagnostically useful marker in distinguishing high-grade neuroendocrine carcinomas from carcinoids.

  13. 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

  14. 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

    2013-10-16

    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 or

  15. 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...

  16. 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....

  17. 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.

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

    Science.gov (United States)

    Ohmoto, Akihiro; Rokutan, Hirofumi; Yachida, Shinichi

    2017-01-01

    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. PMID:28098761

  19. Neuroendocrine carcinoma of the pancreas with soft tissue metastasis

    Institute of Scientific and Technical Information of China (English)

    Jie Chen; Qi Zheng; Zhe Yang; Xin-Yu Huang; Zhou Yuan; Juan Tang

    2012-01-01

    Neuroendocrine carcinoma (NEC) of the pancreas is rare.We report the case of a 34-year-old man with pancreatic NEC with soft tissue metastasis.The patient presented with right upper abdominal discomfort.Computed tomography revealed a low-density heterogeneous mass in the tail and body of the pancreas that encroached on the greater curvature of the stomach and spleen.We performed exploratory laparotomy and total pancreatectomy with splenectomy and total gastrectomy.Histopathological analysis showed spindleshaped cells with scanty cytoplasm and hyperchromatic nuclei,confirming a primary pancreatic NEC.One month after the surgery,the patient experienced leg swelling.Positron emission tomography-computed tomography revealed high uptake of fludeoxyglucose in the left leg,and the leg was amputated.Histopathological analysis confirmed metastasis of pancreatic NEC.The patient was followed up and received chemotherapy (etoposide and cisplatin).One month after amputation,the level of tumor marker neuron-specific enolase was 142.70 μg/L and computed tomography scan revealed an aggravated metastatic lesion.The patient suffered from unbearable pain and we treated him with odynolysis.Four months postoperatively,the patient died of respiratory failure.

  20. Interventional treatment of neuroendocrine liver metastases

    DEFF Research Database (Denmark)

    Knigge, U.; Hansen, C.P.; Stadil, F.

    2008-01-01

    Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases....... The symptomatic response rate is 90% with a mean duration of two years. Liver transplantation should be restricted to very few and highly selected patients without extrahepatic disease. Recurrence is inevitable in nearly all patients Udgivelsesdato: 2008/8...

  1. Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent.

    Science.gov (United States)

    Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood

    2016-01-01

    The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.

  2. Neuroendocrine alterations impair enamel mineralization, tooth eruption and saliva in rats Alterações neuroendócrinas interferem com a mineralização do esmalte, a erupção dentária e a saliva em ratos

    Directory of Open Access Journals (Sweden)

    Kikue Takebayashi Sassaki

    2003-03-01

    Full Text Available Neonatal administration of monosodium glutamate (MSG in rats causes definite neuroendocrine disturbances which lead to alterations in many organ systems. The possibility that MSG could affect tooth and salivary gland physiology was examined in this paper. Male and female pups were injected subcutaneously with MSG (4 mg/g BW once a day at the 2nd, 4th, 6th, 8th and 10th day after birth. Control animals were injected with saline, following the same schedule. Lower incisor eruption was determined between the 4th and the 10th postnatal days, and the eruption rate was measured between the 43rd and the 67th days of age. Pilocarpine-stimulated salivary flow was measured at 3 months of age; protein and amylase contents were thereby determined. The animals treated with MSG showed significant reductions in the salivary flow (males, -27%; females, -40% and in the weight of submandibular glands (about -12%. Body weight reduction was only about 7% for males, and did not vary in females. Saliva of MSG-treated rats had increased concentrations of total proteins and amylase activity. The eruption of lower incisors occurred earlier in MSG-treated rats than in the control group, but on the other hand the eruption rate was significantly slowed down. The incisor microhardness was found to be lower than that of control rats. Our results show that neonatal MSG treatment causes well-defined oral disturbances in adulthood in rats, including salivary flow reduction, which coexisted with unaltered protein synthesis, and disturbances of dental mineralization and eruption. These data support the view that some MSG-sensitive hypothalamic nuclei have an important modulatory effect on the factors which determine caries susceptibility.A administração neonatal de glutamato monossódico (MSG em ratos provoca distúrbios neuroendócrinos que acarretam alterações em vários sistemas orgânicos. Neste trabalho, avaliamos as repercussões desse tratamento sobre dentes e gl

  3. Exercise and neuroendocrine modulation of macrophage function.

    Science.gov (United States)

    Woods, J A

    2000-05-01

    Like all immune cells, Mphi's cannot simply be viewed as individual cells, but as part of a complex network of cells and tissues that communicate in many different ways in an attempt to elicit an appropriate host response to immune and other challenges. Mphi's are important initial effector cells and are highly regulated by other cells (including T and B lymphocytes) and hormones produced by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. Indeed, it may well be that stressors, including exercise, exert their regulatory influence over these cells by activating the SNS, HPA axis, or by influencing other tissues or cells. With this in mind, the overall objective of this review is to introduce and provide current information regarding the role of neuroendocrine factors in mediating exercise-induced changes in macrophage (Mphi) function. Under this broad objective this review will: 1) briefly discuss the cell biology of the Mphi and its role in host defense, 2) explore the potential regulatory influence of selected neuroendocrine hormones (glucocorticoids, catecholamines, growth hormone, prolactin, and beta-endorphin) that may potentially mediate exercise-induced changes in Mphi function, and 3) describe the effects of exercise on the functions of the Mphi.

  4. [Neuroendocrine immune interactions in rheumatic diseases].

    Science.gov (United States)

    Straub, R H; Fassold, A

    2010-06-01

    Clinical observations in chronic inflammatory diseases have demonstrated the significant influence of neuroendocrine mechanisms on the immune system: (1) Amelioration of rheumatoid arthritis during pregnancy; (2) preponderance of women versus men with respect to autoimmune diseases; (3) negative effects of ovulation-inducing therapy, oral contraceptives, and hormone replacement therapy; (4) protective effect of hemiplegia; (5) influence of psychological stress on inflammation; and (6) influence of circadian rhythms on inflammatory symptoms.The effects of different hormones and neurotransmitters on the immune system are influenced by: (1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses, (2) the cell types involved during different phases of the disease, (3) the target organ with its specific microenvironment, (4) the timing of hormone or neurotransmitter increase in relation to the disease course, (5) the concentration of hormones and neurotransmitters, (6) the variability in expression of receptors depending on the microenvironment and the cell type, and (7) the intra- and extracellular peripheral metabolism of hormones and neurotransmitters leading to important biologically active metabolites with quite different anti- and proinflammatory functions.The circadian rhythm of disease-related symptoms with a peak in the early morning hours confirms that the neuroendocrine system has a strong influence on these chronic immune/inflammatory diseases. The influence is transmitted by the circadian fluctuation in the activity of hormonal and neuronal pathways linking the brain to immune cell activation.These considerations could lead to novel therapeutic strategies for rheumatic diseases in the future.

  5. A single dose of histamine-receptor antagonists before downhill running alters markers of muscle damage and delayed-onset muscle soreness.

    Science.gov (United States)

    Ely, Matthew R; Romero, Steven A; Sieck, Dylan C; Mangum, Joshua E; Luttrell, Meredith J; Halliwill, John R

    2017-03-01

    Histamine contributes to elevations in skeletal muscle blood flow following exercise, which raises the possibility that histamine is an important mediator of the inflammatory response to exercise. We examined the influence of antihistamines on postexercise blood flow, inflammation, muscle damage, and delayed-onset muscle soreness (DOMS) in a model of moderate exercise-induced muscle damage. Subjects consumed either a combination of fexofenadine and ranitidine (blockade, n = 12) or nothing (control, n = 12) before 45 min of downhill running (-10% grade). Blood flow to the leg was measured before and throughout 120 min of exercise recovery. Markers of inflammation, muscle damage, and DOMS were obtained before and at 0, 6, 12, 24, 48, and 72 h postexercise. At 60 min postexercise, blood flow was reduced ~29% with blockade compared with control (P < 0.05). Markers of inflammation were elevated after exercise (TNF-ɑ, IL-6), but did not differ between control and blockade. Creatine kinase concentrations peaked 12 h after exercise, and the overall response was greater with blockade (18.3 ± 3.2 kU·l(-1)·h(-1)) compared with control (11.6 ± 2.0 kU·l(-1)·h(-1); P < 0.05). Reductions in muscle strength in control (-19.3 ± 4.3% at 24 h) were greater than blockade (-7.8 ± 4.8%; P < 0.05) and corresponded with greater perceptions of pain/discomfort in control compared with blockade. In conclusion, histamine-receptor blockade reduced postexercise blood flow, had no effect on the pattern of inflammatory markers, increased serum creatine kinase concentrations, attenuated muscle strength loss, and reduced pain perception following muscle-damaging exercise.NEW & NOTEWORTHY Histamine appears to be intimately involved with skeletal muscle during and following exercise. Blocking histamine's actions during muscle-damaging exercise, via common over-the-counter antihistamines, resulted in increased serum creatine kinase, an indirect marker of muscle damage. Paradoxically, blocking

  6. Salvage treatment after r-interferon [alpha]-2a in advanced neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zilembo, N. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Buzzoni, R. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Bajetta, E. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Di Bartolomeo, M. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); De Braud, F. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Castellani, R. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Maffioli, L. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Celio, L. (Italian Trials in Medical

    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 [alpha]-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[sup 2] intravenously days 1, 2, 3 and epirubicin 75 mg/m[sup 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.).

  7. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  8. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy.

    Science.gov (United States)

    Yip, Linwah

    2015-01-01

    Molecular markers including gene expression profiles, somatic gene alterations, and circulating peripheral markers have augmented diagnostic, prognostic, and therapeutic options for thyroid cancer patients.

  9. 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.

  10. Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Myhr, Kjell-Morten; Løken-Amsrud, Kristin Ingeleiv; Bakke, Søren Jacob; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Benth, Jūratė Saltytė; Torkildsen, Øivind; Wergeland, Stig; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Holmøy, Trygve

    2014-06-15

    To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-β1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-β1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-β1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-β1a treatment.

  11. Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    Science.gov (United States)

    Kamimura, Mikio; Uchiyama, Shigeharu; Nakamura, Yukio; Ikegami, Shota; Mukaiyama, Keijiro; Kato, Hiroyuki

    2017-01-01

    This study aimed to clarify the effects of short-term bisphosphonate (BP) administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN) at 1 mg/day (MIN group) or weekly risedronate (RIS) at 17.5 mg/week (RIS group) was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS) before the start of treatment and at 4 months afterward. The changes in 25(OH)D3, whole parathyroid hormone (PTH), serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX), serum tartrate-resistant acid phosphatase (TRACP)-5b, bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OH)D3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of −14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 μg/mL, with a percent change of 15.2%. In group comparisons, 25(OH)D3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS.

  12. Marker development

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  13. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    Science.gov (United States)

    Brabander, Tessa; Teunissen, Jaap J M; Van Eijck, Casper H J; Franssen, Gaston J H; Feelders, Richard A; de Herder, Wouter W; Kwekkeboom, Dik J

    2016-01-01

    In the past decades, the number of neuroendocrine tumours that are detected is increasing. A relative new and promising therapy for patients with metastasised or inoperable disease is peptide receptor radionuclide therapy (PRRT). This therapy involves an infusion of somatostatin analogues linked to radionuclides like Yttrium-90 or Lutetium-177. Objective response rates are reported in 15-35%. Response rates may vary between type of tumour and radionuclide. Besides the objective response rate, overall survival and progression free survival increase significantly. Also, the quality of life improves as well. Serious side-affects are rare. PRRT is usually well tolerated, also in patients with extensive metastasised disease. Recent studies combined PRRT with other types of therapies. Unfortunately no randomised trials comparing these strategies are available. In the future, more research is needed to evaluate the best therapy combinations or sequence of therapies.

  14. New drug development in digestive neuroendocrine tumors.

    Science.gov (United States)

    Durán, I; Salazar, R; Casanovas, O; Arrazubi, V; Vilar, E; Siu, L L; Yao, J; Tabernero, J

    2007-08-01

    The traditional cytotoxic agents are of limited efficacy in the treatment of neuroendocrine tumors of the gastrointestinal tract (NETs). Recent investigations have brought up a number of biological features in this family of neoplasms that could represent targets for anticancer treatment. NETs seem to have an extraordinary tumor vascularization with high expression of proangiogenic molecules such as the vascular endothelial growth factor along with overexpression of certain tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR), the insulin growth factor receptor (IGFR) and their downstream signaling pathway components (PI3K-AKT-mTOR). The rationale of an antiangiogenic approach in the treatment of NETs and the use of other pharmacological strategies such as EGFR, IGFR and mammalian target of rapamycin inhibitors are discussed. Additionally, the emerging results of recent clinical trials with these targeted drugs are presented.

  15. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  16. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ehehalt, Florian, E-mail: florian.ehehalt@uniklinikum-dresden.de; Franke, Ellen; Pilarsky, Christian; Grützmann, Robert [Department for General, Thoracic and Vascular Surgery, University Hospital “Carl Gustav Carus”, University of Technology, Dresden (Germany)

    2010-11-18

    Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management.

  17. Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

    Science.gov (United States)

    Pokuri, Venkata K; Fong, Mei Ka; Iyer, Renuka

    2016-01-01

    Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.

  18. Neuroendocrine disruption of organizational and activational hormone programming in poikilothermic vertebrates.

    Science.gov (United States)

    Rosenfeld, Cheryl S; Denslow, Nancy D; Orlando, Edward F; Gutierrez-Villagomez, Juan Manuel; Trudeau, Vance L

    2017-01-01

    In vertebrates, sexual differentiation of the reproductive system and brain is tightly orchestrated by organizational and activational effects of endogenous hormones. In mammals and birds, the organizational period is typified by a surge of sex hormones during differentiation of specific neural circuits; whereas activational effects are dependent upon later increases in these same hormones at sexual maturation. Depending on the reproductive organ or brain region, initial programming events may be modulated by androgens or require conversion of androgens to estrogens. The prevailing notion based upon findings in mammalian models is that male brain is sculpted to undergo masculinization and defeminization. In absence of these responses, the female brain develops. While timing of organizational and activational events vary across taxa, there are shared features. Further, exposure of different animal models to environmental chemicals such as xenoestrogens such as bisphenol A-BPA and ethinylestradiol-EE2, gestagens, and thyroid hormone disruptors, broadly classified as neuroendocrine disrupting chemicals (NED), during these critical periods may result in similar alterations in brain structure, function, and consequently, behaviors. Organizational effects of neuroendocrine systems in mammals and birds appear to be permanent, whereas teleost fish neuroendocrine systems exhibit plasticity. While there are fewer NED studies in amphibians and reptiles, data suggest that NED disrupt normal organizational-activational effects of endogenous hormones, although it remains to be determined if these disturbances are reversible. The aim of this review is to examine how various environmental chemicals may interrupt normal organizational and activational events in poikilothermic vertebrates. By altering such processes, these chemicals may affect reproductive health of an animal and result in compromised populations and ecosystem-level effects.

  19. Neuroendocrine perspectives on social attachment and love.

    Science.gov (United States)

    Carter, C S

    1998-11-01

    The purpose of this paper is to review existing behavioral and neuroendocrine perspectives on social attachment and love. Both love and social attachments function to facilitate reproduction, provide a sense of safety, and reduce anxiety or stress. Because social attachment is an essential component of love, understanding attachment formation is an important step toward identifying the neurobiological substrates of love. Studies of pair bonding in monogamous rodents, such as prairie voles, and maternal attachment in precocial ungulates offer the most accessible animal models for the study of mechanisms underlying selective social attachments and the propensity to develop social bonds. Parental behavior and sexual behavior, even in the absence of selective social behaviors, are associated with the concept of love; the analysis of reproductive behaviors, which is far more extensive than our understanding of social attachment, also suggests neuroendocrine substrates for love. A review of these literatures reveals a recurrent association between high levels of activity in the hypothalamic pituitary adrenal (HPA) axis and the subsequent expression of social behaviors and attachments. Positive social behaviors, including social bonds, may reduce HPA axis activity, while in some cases negative social interactions can have the opposite effect. Central neuropeptides, and especially oxytocin and vasopressin have been implicated both in social bonding and in the central control of the HPA axis. In prairie voles, which show clear evidence of pair bonds, oxytocin is capable of increasing positive social behaviors and both oxytocin and social interactions reduce activity in the HPA axis. Social interactions and attachment involve endocrine systems capable of decreasing HPA reactivity and modulating the autonomic nervous system, perhaps accounting for health benefits that are attributed to loving relationships.

  20. Prenatal programming of neuroendocrine reproductive function.

    Science.gov (United States)

    Evans, Neil P; Bellingham, Michelle; Robinson, Jane E

    2016-07-01

    It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the "prenatal programming" of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be "shaped" both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent "normal function". The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on

  1. Short-term bisphosphonate treatment reduces serum 25(OH vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    Directory of Open Access Journals (Sweden)

    Kamimura M

    2017-02-01

    Full Text Available Mikio Kamimura,1 Shigeharu Uchiyama,2 Yukio Nakamura,2,3 Shota Ikegami,2 Keijiro Mukaiyama,2 Hiroyuki Kato2 1Center for Osteoporosis and Spinal Disorders, Kamimura Orthopaedic Clinic, Matsumoto, Japan; 2Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 3Department of Orthopedic Surgery, Showa-Inan General Hospital, Komagane, Japan Abstract: This study aimed to clarify the effects of short-term bisphosphonate (BP administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN at 1 mg/day (MIN group or weekly risedronate (RIS at 17.5 mg/week (RIS group was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS before the start of treatment and at 4 months afterward. The changes in 25(OHD3, whole parathyroid hormone (PTH, serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX, serum tartrate-resistant acid phosphatase (TRACP-5b, bone-specific alkaline phosphatase (BAP, and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OHD3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of –14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 µg/mL, with a percent change of 15.2%. In group comparisons, 25(OHD3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OHD3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and

  2. Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers.

    Science.gov (United States)

    Shah, D K; Khandavilli, S; Panchagnula, R

    2008-09-01

    Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well

  3. 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.

  4. Benign gastric neuroendocrine tumors in three snow leopards (Panthera uncia).

    Science.gov (United States)

    Dobson, Elizabeth C; Naydan, Dianne K; Raphael, Bonnie L; McAloose, Denise

    2013-06-01

    Neuroendocrine tumors are relatively rare neoplasms arising from neuroendocrine cells that are distributed throughout the body and are predominant in the gastrointestinal tract. This report describes benign, well-differentiated gastric neuroendocrine tumors in three captive snow leopards (Panthera uncia). All tumors were well circumscribed, were within the gastric mucosa or submucosa, and had histologic and immunohistochemical features of neuroendocrine tumors. Histologic features included packeted cuboidal to columnar epithelial cells that were arranged in palisades or pseudorosettes and contained finely granular cellular cytoplasm with centrally placed, round nuclei. Cytoplasmic granules of neoplastic cells strongly expressed chromogranin A, variably expressed neuron-specific enolase, and did not express synaptophysin or gastrin. Each leopard died or was euthanatized for reasons unrelated to its tumor.

  5. HIF Signaling Pathway in Pheochromocytoma and Other Neuroendocrine Tumors

    National Research Council Canada - National Science Library

    I Jochmanová; T Zelinka; J Widimský Jr; K Pacak

    2014-01-01

    .... Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheochromocytoma (PHEO) and paraganglioma (PGL...

  6. 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.

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

    African Journals Online (AJOL)

    Primary neuroendocrine carcinoma (PNEC) of breast were an unknown .... treatment is limited to surgery such as MRM with axillary clearance,[1,3] which ... carcinoma of the breast: Diagnostic and clinical implications. Anticancer Res 2012 ...

  8. Neuroendocrine cells in the urogenital tract of the buffalo

    Directory of Open Access Journals (Sweden)

    A. Vittoria

    2010-02-01

    Full Text Available Neuroendocrine cells or paraneurons are cytotypes producing biogenic amines and/or hormonal peptides, scattered in the glandular and lining epithelia of the body. In this study the presence of chromogranin A-, serotonin- and somatostatin-immunoreactive neuroendocrine cells has been described immunohistochemically in the urethro- prostatic complex and female urethra of subjects of the buffalo Bubalus bubalis. The chromogranin A- containing neuroendocrine cells resulted the most numerous cytotype, the serotonin- containing ones the most irregular in shape for the presence of dendritic-like cytoplasmic extensions and the somatostatin- containing the rarest. The role played by the amine serotonin in the genital tract has been related to the determinism of sexual climax and to the contraction of smooth muscle. The function played by the neuroendocrine genital somatostatin is unknown. Analogically to what described for the same gastrointestinal hormone, it could inhibit both exocrine and endocrine secretions.

  9. Orbital metastases from neuroendocrine carcinoma, masquerading as graves orbitopathy.

    Science.gov (United States)

    Sira, Mano; Clauss, Ralf P; Maclean, Chris; Rose, Geoffrey E

    2010-04-01

    We describe a patient with metastases from neuroendocrine carcinoma masquerading as Graves ophthalmopathy. This rare tumour possibly has a propensity for orbital spread, and we postulate a mechanism evoking the 'seed and soil' hypothesis.

  10. Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.

    Directory of Open Access Journals (Sweden)

    Thomas Paccalet

    Full Text Available OBJECTIVE: HIBM (Hereditary Inclusion Body Myopathy is a recessive hereditary disease characterized by adult-onset, slowly progressive muscle weakness sparing the quadriceps. It is caused by a single missense mutation of each allele of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE gene, a bifunctional enzyme catalyzing the first two steps of sialic acid synthesis in mammals. However, the mechanisms and cellular pathways affected by the GNE mutation and causing the muscle weakness could not be identified so far. Based on recent evidence in literature, we investigated a new hypothesis, i.e. the involvement in the disease of the GM3 ganglioside, a specific glycolipid implicated in muscle cell proliferation and differentiation. METHODS: qRT-PCR analysis of St3gal5 (GM3 synthase gene expression and HPLC quantification of GM3 ganglioside were conducted on muscle tissue from a mouse model of HIBM harboring the M712T mutation of GNE (Gne(M712T/M712T mouse vs control mice (Gne(+/+ mouse. RESULTS: St3gal5 mRNA levels were significantly lower in Gne(M712T/M712T mouse muscles vs Gne(+/+ mouse muscles (64.41%+/-10% of Gne(+/+ levels. GM3 ganglioside levels showed also a significant decrease in Gne(M712T/M712T mouse muscle compared to Gne(+/+ mouse muscle (18.09%+/-5.33% of Gne(+/+ levels. Although these Gne(M712T/M712T mice were described to suffer severe glomerular proteinuria, no GM3 alterations were noted in kidneys, highlighting a tissue specific alteration of gangliosides. CONCLUSION: The M712T mutation of GNE hampers the muscle ability to synthesize normal levels of GM3. This is the first time that a mutation of GNE can be related to the molecular pathological mechanism of HIBM.

  11. Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

    Science.gov (United States)

    Ohara, Yusuke; Oda, Tatsuya; Hashimoto, Shinji; Akashi, Yoshimasa; Miyamoto, Ryoichi; Enomoto, Tsuyoshi; Satomi, Kaishi; Morishita, Yukio; Ohkohchi, Nobuhiro

    2016-01-01

    AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis. METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin. RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles. CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

  12. Supplementation with fruit and vegetable soups and beverages increases plasma carotenoid concentrations but does not alter markers of oxidative stress or cardiovascular risk factors.

    Science.gov (United States)

    Paterson, Elaine; Gordon, Michael H; Niwat, Chutamat; George, Trevor W; Parr, Laura; Waroonphan, Saran; Lovegrove, Julie A

    2006-11-01

    This study was aimed at determining whether an increase of 5 portions of fruits and vegetables in the form of soups and beverages has a beneficial effect on markers of oxidative stress and cardiovascular disease risk factors. The study was a single blind, randomized, controlled, crossover dietary intervention study. After a 2-wk run-in period with fish oil supplementation, which continued throughout the dietary intervention to increase oxidative stress, the volunteers consumed carotenoid-rich or control vegetable soups and beverages for 4 wk. After a 10-wk wash-out period, the volunteers repeated the above protocol, consuming the other intervention foods. Both test and control interventions significantly increased the % energy from carbohydrates and decreased dietary protein and vitamin B-12 intakes. Compared with the control treatment, consumption of the carotenoid-rich soups and beverages increased dietary carotenoids, vitamin C, alpha-tocopherol, potassium, and folate, and the plasma concentrations of alpha-carotene (362%), beta-carotene (250%) and lycopene (31%) (P oxidative stress were not affected by treatment. Consumption of fruit and vegetable soups and beverages makes a useful contribution to meeting dietary recommendations for fruit and vegetable consumption.

  13. A case of an intussuscepted neuroendocrine carcinoma of the appendix

    Institute of Scientific and Technical Information of China (English)

    Rachel E Thomas; Karen Maude; Olorunda Rotimi

    2006-01-01

    We have described a previously unreported entity of an intussuscepted neuroendocrine carcinoma of the appendix. Our patient was a 70-year-old man whose only complaint was insipient weight loss. Colonoscopy showed a malignant cecal "polyp", and an extended right hemicolectomy was performed. We have reviewed the literature on the causes of appendiceal intussusception and their appropriate treatment options, and clarified the classification of neuroendocrine tumors of the gastrointestinal tract.

  14. Genetics and epigenetics in small intestinal neuroendocrine tumours.

    Science.gov (United States)

    Stålberg, P; Westin, G; Thirlwell, C

    2016-12-01

    Neuroendocrine tumour of the small intestine (SI-NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI-NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5-year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60-90% of SI-NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI-NETs but, with a frequency as low as 8%, its role as a driver in SI-NET development may be questioned. Integrated genomewide analysis including exome and whole-genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI-NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI-NETs have significant epigenetic dysregulation in 70-80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI-NETs.

  15. [Contemporary management of neuroendocrine neoplasms of the female genital organs].

    Science.gov (United States)

    Kuc-Rajca, Małgorzata; Dańska-Bidzińska, Anna

    2011-09-01

    Neuroendocrine neoplasms are a rare and heterogeneous group of diseases that account for only 2% of all gynecologic malignancies. The most common types are ovarian carcinoid tumor and small cell neuroendocrine carcinoma of the cervix. The tumors are staged according to FIGO clinical staging system. The diagnosis is usually made retrospectively after obtaining the results of histopathological evaluation of the primary tumor They rarely cause syndromes related to hormone overexpression. Neuroendocrine neoplasms are characterized by aggressive behaviour Even at an early stage there is high incidence of nodal and distant metastases. Survival is poor regardless of stage at diagnosis. The most important is to diagnose the neuroendocrine tumor accurately and treat it in multimodal, aggressive approach to control the disease better and reduce the incidence of reccurences. Apart from typical therapeutic approach, treatment may encompass isotope therapy using radiolabeled somatostatin analogs. This method should be reserved for patients with expression of somatostatin receptors detected by the somatostatin receptor scyntygraphy. Data concerning the management of neuroendocrin tumors are based mainly on retrospective studies and clinical case series. Lack of randomized trials makes it impossible to select the best treatment option. Better understanding of the biology of neuroendocrine tumors, especially the molecular genetics, will in the future help to determine the optimal treatment strategies for these tumors.

  16. Clinical utility of lanreotide Autogel® in gastroenteropancreatic neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Paragliola RM

    2016-10-01

    Full Text Available Rosa Maria Paragliola,1 Alessandro Prete,1 Giampaolo Papi,1 Francesco Torino,2 Andrea Corsello,3 Alfredo Pontecorvi,1 Salvatore Maria Corsello1 1Department of Medicine, Unit of Endocrinology, Università Cattolica del Sacro Cuore, 2Department of Systems Medicine, Tor Vergata University, Rome, 3Department of General Medicine and Endocrine Tumor Unit, San Raffaele Scientific Institute, Milan, Italy Abstract: Somatostatin analogs (SSAs, which were initially used to control hormonal syndromes associated with neuroendocrine neoplasms (NENs, have been successfully proposed as antiproliferative agents, able to control tumor growth in patients affected by gastroenteropancreatic (GEP-NENs. The development of long-acting formulations of SSAs which require only weekly or monthly injections can improve patient compliance. In particular, lanreotide (LAN Autogel®, which is a viscous aqueous formulation supplied in ready-to-use prefilled syringes, can be administered every 28–56 days. Since its introduction in the clinical practice, several studies evaluated the clinical utility of LAN Autogel in the medical treatment of GEP-NENs. Although there is no evidence of an overall survival benefit, these studies confirm the efficacy of LAN Autogel in terms of benefit in progression-free survival, and in more than half of cases, a reduction of tumor markers can be observed during treatment with this drug. Moreover, LAN Autogel is widely recognized to be effective in controlling tumor-related symptoms in the majority of patients affected by GEP tumors, especially in patients affected by carcinoid syndrome, improving considerably patients’ quality of life. Keywords: lanreotide Autogel, gastroenteropancreatic neuroendocrine tumors, gastroenteropancreatic neuroendocrine neoplasms, somatostatin analogs

  17. Midkine is associated with neuroendocrine differentiation in castration-resistant prostate cancer.

    Science.gov (United States)

    Nordin, Anna; Wang, Wanzhong; Welén, Karin; Damber, Jan-Erik

    2013-05-01

    Castration-resistant prostate cancer (CRPC) is an incurable disease and both androgen-deprivation therapy (ADT) and neuroendocrine differentiation (NED) are closely related to CRPC transition. More knowledge concerning neuroendocrine (NE)-transformed PC cells, the NED process and its association with CRPC, is needed. Expression of growth factor midkine (MDK) is correlated with poor clinical outcomes in various human cancers, including PC. In the present study, we have evaluated MDK expression and NED in two separate tumor groups: early and advanced PC. Immunohistochemical analysis of MDK, the neuronal marker tubulin-beta III (TUBB3) and the NE-marker chromogranin A (CGA) in a human archival material consisting of hormone naive (HN)/stage T1b (n = 29) and CRPC (n = 24) tumors. Triple immunofluorescent imaging was performed on a selection of specimens. MDK, TUBB3, and CGA were upregulated in CRPC compared to HN tumors. MDK was highly associated to the expression of both CGA and TUBB3, and identified MDK-positive NE-like looking cells found to co-express CGA or, more commonly, CGA together with TUBB3. CGA and TUBB3 staining displayed a partial expression overlap, an overlap almost exclusively displaying also MDK expression. MDK upregulation in CRPC is associated with NED (shown by its relation to CGA and TUBB3). The results suggest that MDK represents an over-bridging marker between different populations of NE-like tumor cells, possibly as part of the NED process and associated CRPC transition, something that needs to be evaluated experimentally as does the applicability of MDK as a future target. Copyright © 2012 Wiley Periodicals, Inc.

  18. Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation.

    Science.gov (United States)

    Ishii, Jun; Sato, Hanako; Yazawa, Takuya; Shishido-Hara, Yukiko; Hiramatsu, Chie; Nakatani, Yukio; Kamma, Hiroshi

    2014-09-01

    One-third of lung malignancies demonstrate a proneural/neuroendocrine phenotype or type of differentiation. However, it has not been clearly elucidated how proneural/neuroendocrine differentiation is controlled in lung cancers. We recently demonstrated that the POU3F2 gene plays a significant role in proneural/neuroendocrine differentiation of lung cancers. Because class III POU genes (POU3F1, POU3F2, POU3F3, and POU3F4) and class IV POU genes (POU4F1, POU4F2, and POU4F3) share similar properties in neural development, we analyzed the association between class III/IV POU genes and a proneural/neuroendocrine phenotype in lung cancers using seven small cell lung cancer (SCLC) cell lines and twelve non-SCLC (NSCLC) cell lines. Class III/IV POU gene expression was generally restricted to SCLC cells. However, the forced expression of class III/IV POU genes in the NSCLC cell lines induced the expression of neuroendocrine-specific markers (neural call adhesion molecule 1, synaptophysin, and chromogranin A) and proneural transcription factors (achaete-scute homolog-like 1, NeuroD1, and thyroid transcription factor 1) in various degrees. Furthermore, each class III/IV POU gene induced other class III/IV POU genes, suggesting the mutual induction of class III/IV POU genes. These findings suggest that the expression of class III/IV POU genes is important for the proneural/neuroendocrine differentiation of lung cancer cells.

  19. Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-11-01

    cancer. Its methylation leads to abrogation of SFRP2 expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of SFRP2. Although clinical patient outcome was not associated with SFRP2 methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify SFRP2 promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.

  20. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Kos-Kudła, Beata; Blicharz-Dorniak, Jolanta; Handkiewicz-Junak, Daria; Jarząb, Barbara; Jarząb, Michał; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Król, Robert; Królicki, Leszek; Krzakowski, Maciej; Nasierowska-Guttmejer, Anna; Nowakowska-Duława, Ewa; Patkowski, Waldemar; Szawłowski, Andrzej W

    2013-01-01

    An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

  1. Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function.

    Science.gov (United States)

    Azzinnari, Damiano; Sigrist, Hannes; Staehli, Simon; Palme, Rupert; Hildebrandt, Tobias; Leparc, German; Hengerer, Bastian; Seifritz, Erich; Pryce, Christopher R

    2014-10-01

    In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Altered Synaptic Marker Abundance in the Hippocampal Stratum Oriens of Ts65Dn Mice is Associated with Exuberant Expression of Versican

    Directory of Open Access Journals (Sweden)

    Matthew D Howell

    2012-01-01

    Full Text Available DS (Down syndrome, resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans in the ECM (extracellular matrix can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls. In young (5 months old Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95 compared with LMCs. In aged (20 months old Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets, an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits.

  3. Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

    Directory of Open Access Journals (Sweden)

    Paul E Gottschall

    2012-02-01

    Full Text Available DS (Down syndrome, resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans in the ECM (extracellular matrix can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls. In young (5 months old Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95 compared with LMCs. In aged (20 months old Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets, an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits.

  4. Leptin intake in suckling rats restores altered T3 levels and markers of adipose tissue sympathetic drive and function caused by gestational calorie restriction.

    Science.gov (United States)

    Konieczna, J; Palou, M; Sánchez, J; Picó, C; Palou, A

    2015-06-01

    Maternal calorie restriction during gestation in rats has been associated with altered white adipose tissue (WAT) sympathetic innervation and function in offspring. Here, we aimed to investigate whether supplementation with oral leptin (a breast milk component) throughout the lactation period may revert the aforementioned adverse programming effects. Three groups of male and female rats were studied at the postnatal day 25: the offspring of control dams, the offspring of 20% calorie-restricted dams during pregnancy (CR) and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Tyrosine hydroxylase (TH) levels and its immunoreactive area, and mRNA expression levels of lipid metabolism-related genes and of deiodinase iodothyronine type II (Dio2) were determined in WAT. Triiodothyronine (T3) levels were determined in the blood. In CR males, leptin treatment restored the decreased TH levels and its immunoreactive area in WAT, and partially normalized expression levels of genes related to lipolysis and fatty acid oxidation (adipose triglyceride lipase, hormone-sensitive lipase, carnitine palmitoyltransferase 1b and peroxisome proliferator-activated receptor gamma coactivator 1-alpha). Leptin treatment also reverted the decreased T3 plasma levels and WAT lipoprotein lipase mRNA levels occurring in CR males and females, and the decreased Dio2 mRNA levels in CR females. Leptin supplementation throughout the lactation period reverts the malprogrammed effects on WAT structure and function induced by undernutrition during pregnancy. These findings support the relevance of the intake of leptin during lactation, bearing clear characteristics of essential nutrient, and provide a strategy to treat and/or prevent the programmed trend to obesity acquired by inadequate fetal nutrition.

  5. Rectal neuroendocrine tumor with uncommon metastatic spread: A case report and review of literature.

    Science.gov (United States)

    Tsoukalas, Nikolaos; Galanopoulos, Michail; Tolia, Maria; Kiakou, Maria; Nakos, Georgios; Papakostidi, Aristoula; Koumakis, Georgios

    2016-02-15

    Neuroendocrine tumors of the gastrointestinal tract are rare neoplasms. Rectal neuroendocrine tumors consist approximately the 5%-14% of all neuroendocrine neoplasms in Europe. These tumors are diagnosed in relatively young patients, with a mean age at diagnosis of 56 years. Distant metastases from rectal neuroendocrine tumors are not very common. Herein we describe a case of a rectal neuroendocrine tumor which metastasized to the lung, mediastinum and orbit. This case underscores the importance of early identification and optimal management to improve patient's prognosis. Therefore, the clinical significance of this case is the necessity of physicians' awareness and education regarding neuroendocrine tumors' diagnosis and management.

  6. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

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

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  7. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  8. Pulmonary neuroendocrine cell hyperplasia: identification, diagnostic criteria and incidence in untreated ageing rats of different strains.

    Science.gov (United States)

    Haworth, Richard; Woodfine, Jennie; McCawley, Sean; Pilling, Andrew M; Lewis, David J; Williams, Tom C

    2007-08-01

    Pulmonary Neuroendocrine Cells (PNEC) are found as clusters called neuroepithelial bodies (NEB) or as single cells scattered in the respiratory epithelium. Pulmonary neuroendocrine cell hyperplasia is recorded in humans and experimentally manipulated rodents. The objectives of this work were to identify the optimal immunohistochemical markers for PNEC in the rat for use on paraffin-embedded, formalin-fixed material and to provide the first comparative incidence of PNEC hyperplasia in untreated 2-year-old rats of different strains. Calcitonin-gene related peptide (CGRP) and protein G product 9.5 (PGP9.5) antibodies identified PNEC consistently and selectively. In contrast, PNEC did not express chromogranin-A or S-100. PNEC hyperplasia was defined as foci of PNEC with greater than 40 nuclei, excluding overlying respiratory epithelium and submucosal PNEC. PNEC hyperplasia was observed at low incidence (0-7%) in untreated 2-year-old Sprague-Dawley, Han Wistar and Wistar rats but not Fischer 344 rats. This is the first report of spontaneous PNEC hyperplasia in rats. The cause of this hyperplasia is unknown, but experimental models that induce PNEC hyperplasia by causing bronchiolar cell injury are discussed. PNEC neoplasia in the rat is unreported in the literature and was not observed in animals examined in this study.

  9. 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.

  10. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy

    Science.gov (United States)

    Montanier, Nathanaëlle; Joubert-Zakeyh, Juliette; Pétorin, Caroline; Montoriol, Pierre François; Maqdasy, Salwan; Kelly, Antony

    2017-01-01

    Abstract Rationale: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. Diagnoses and interventions: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (177Lu DOTATATE). Outcomes: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%–70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. Lessons: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy. PMID:28178157

  11. Psychological and neuroendocrine reactivity to ostracism.

    Science.gov (United States)

    Zwolinski, Jennifer

    2012-01-01

    This study used the ostracism detection theory to investigate how ostracism impacts individuals in two ways: (1) immediate poststressor needs, mood, ruminative thoughts, and desire to affiliate, and (2) short-term affective and cortisol reactivity. A total of 58 college students were randomly assigned to the inclusion or ostracism conditions of Cyberball, a virtual ball-tossing game. Immediately following the experimental manipulation, ostracized participants reported more thwarted psychological need states, more negative mood, and fewer positive ruminative thoughts, relative to their included counterparts. Ostracized participants reported a greater interest in affiliating with others in online or in-person settings. In the short-term, ostracized males reported more hostility than included males, although the scores were within expected norms for most males. There was no relation between Cyberball condition and gender across time for depression, anxiety, or positive affect. Approximately 20 min after the onset of the stressor, women in the luteal phase and women taking oral contraceptives in the ostracized group displayed higher cortisol than their counterparts in the included group. Relative to baseline, however, cortisol did not reliably increase after the onset of the stressor. Ostracized females taking oral contraceptives showed the greatest decline in cortisol, compared to included oral contraceptive users. Overall, results suggest that most of the negative effects of ostracism are immediate and limited to psychological, not neuroendocrine, responses.

  12. [Neuroendocrine changes in chronic cardiac insufficiency].

    Science.gov (United States)

    Jaeger, P; Cohen-Solal, A; Dahan, M; Juliard, J M; Charlier, P; Gourgon, R

    1988-02-01

    Throughout the course of chronic congestive heart failure cardiac and peripheral compensatory mechanisms are at play, most of them under the influence of the neuroendocrine system. The reserves of heart rate and contractility are regulated essentially by the noradrenergic system (NAS), but this mechanism is partial and transient owing to the gradual decrease in the density and sensitivity of myocardial beta-adrenergic receptors induced by overstimulation. Adaptation of the heart to exercise may be reduced. This escape phenomenon is also observed with almost all cardiotonic drugs which interfere with cyclic adenosine monophosphate (cAMP), in contrast with the paradoxically favourable effects of beta-blockers in small doses or of drugs that are both agonists and antagonists of beta-adrenergic receptors. The mechanisms which contribute to the induction of left ventricular hypertrophy are imperfectly known. The noradrenergic system and the renin-angiotensin-aldosterone system (RAAS) are probably not the only ones involved. The setting in action of Frank-Sterling heterometric regulation, at first during exercise then permanently, requires an increase in filling pressure obtained by venous constriction (predominantly controlled by the NAS) and, mostly, by an increase in circulating blood volume. NAS and RAAS intervene in the kidneys to produce water-and-salt retention.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Aggressive surgery for metastatic liver neuroendocrine tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Warren, Robert S; Kelly, Mary G; Zuraek, Marlene B; Jensen, Robert T

    2003-12-01

    Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET.

  14. Role of radiotherapy for pancreatobiliary neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Shim; Choi, Jin Hyun; Choi, Chihwan; Seong, Jinsil [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    We investigated the role of radiotherapy (RT) for pancreatobiliary neuroendocrine tumors (PB-NETs). We identified 9 patients with PB-NETs who received RT between January 2005 and March 2012. Of these 9 patients, 4 were diagnosed with NETs in the pancreas and 5 were diagnosed with NETs in the gallbladder. All patients received RT to the primary tumor or resection bed with a median total irradiation dose of 50.4 Gy, with or without chemotherapy. The tumor response rate and tumor control rate in the RT field were 60% and 100 %, respectively. All 4 patients who underwent surgery had no evidence of disease in the RT field. Of the 5 patients who received RT to the primary gross tumor, 1 had complete response, 2 had partial response, and 2 had stable disease in the RT field. The median time to progression was 11 months. Of the 9 patients, four patients had no progression, and 5 patients had progression of disease (locoregional, 2; distant, 2; locoregional/distant, 1). Of the 4 patients without progression, 3 were treated with RT in adjuvant or neoadjuvant setting, and one received RT to primary tumor. One patient experienced radiation-induced duodenitis at 3 months after concurrent chemoradiation without treatment-related mortality. RT can yield local control for advanced PB-NETs. RT should be considered an essential part of multimodality treatment in management of advanced PB-NETs.

  15. 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.)

  16. Primary hepatic neuroendocrine tumor: A case report

    Science.gov (United States)

    MORISHITA, ASAHIRO; YONEYAMA, HIROHITO; NOMURA, TAKAKO; SAKAMOTO, TEPPEI; FUJITA, KOJI; TANI, JOJI; MIYOSHI, HISAAKI; HABA, REIJI; MASAKI, TSUTOMU

    2016-01-01

    We herein present a case of an 87-year-old patient with multiple liver tumors identified on abdominal ultrasound. The assessment performed on admission included physical examination, computed tomography (CT) during hepatic angiography and CT during arterial portography. The examination revealed contrast enhancement of a proportion of the liver tumors (20 mm maximum diameter) during the arterial phase and mild contrast washout of those tumors during the delayed phase. On contrast-enhanced magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, certain liver tumors exhibited contrast enhancement during the early phase and contrast washout during the hepatocyte phase in both lobes. By contrast, no lesions were identified during positron emission tomography imaging of the liver. A liver biopsy was performed and immunohistochemical staining revealed enhanced expression of cytokeratin AE1/AE3, synaptophysin, chromogranin A and CD56 and no expression of hepatocyte antigen or CΚ7. The mindbomb E3 ubiquitin protein ligase-1 index was ~2% in most of the tumor. The liver tumors were finally diagnosed as multiple intrahepatic metastases from a primary hepatic neuroendocrine tumor (PHNET). The patient underwent transarterial chemoembolisation with a combination of miriplatin (84 mg) mixed with gelatin sponge particles and lipiodol. To the best of our knowledge, this is the first report of PHNET in an patient aged >85 years. PMID:27284429

  17. Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish

    Directory of Open Access Journals (Sweden)

    Baier Herwig

    2009-06-01

    Full Text Available Abstract Background Regulated secretion of specialized neuropeptides in the vertebrate neuroendocrine system is critical for ensuring physiological homeostasis. Expression of these cell-specific peptide markers in the differentiating hypothalamus commences prior to birth, often predating the physiological demand for secreted neuropeptides. The conserved function and spatial expression of hypothalamic peptides in vertebrates prompted us to search for critical neuroendocrine genes in newly hatched zebrafish larvae. Results We screened mutant 5 days post-fertilization zebrafish larvae that fail to undergo visually mediated background adaptation for disruption in hypothalamic pomc expression. To our surprise, the ATPase N-ethylmaleimide sensitive factor (nsf was identified as an essential gene for maintenance of neuroendocrine transcriptional programs during the embryo-to-larva transition. Despite normal hypothalamic development in nsfst53 mutants, neuropeptidergic cells exhibited a dramatic loss of cell-specific markers by 5 days post-fertilization that is accompanied by elevated intracellular neuropeptide protein. Consistent with the role of NSF in vesicle-membrane fusion events and intracellular trafficking, cytoplasmic endoplasmic reticulum-like membranes accumulate in nsf-/- hypothalamic neurons similar to that observed for SEC18 (nsf ortholog yeast mutants. Our data support a model in which unspent neuropeptide cargo feedbacks to extinguish transcription in neuropeptidergic cells just as they become functionally required. In support of this model we found that gnrh3 transcripts remained unchanged in pre-migratory, non-functional gonadotropin-releasing hormone (GnRH neurons in nsf-/- zebrafish. Furthermore, oxytocin-like (oxtl, intp transcripts, which are found in osmoreceptive neurons and persist in mutant zebrafish, drop precipitously after mutant zebrafish are acutely challenged with high salt. Conclusion Our analyses of nsf mutant zebrafish

  18. Middle ear adenoma. A tumor displaying mucinous and neuroendocrine differentiation.

    Science.gov (United States)

    Wassef, M; Kanavaros, P; Polivka, M; Nemeth, J; Monteil, J P; Frachet, B; Tran Ba Huy, P

    1989-10-01

    Middle ear adenoma (MEA) is a distinctive, rare entity that appears to be derived from the lining epithelium of the middle ear mucosa. We report four cases of MEA displaying the typical histologic growth pattern. Two distinct tumor cell immunophenotypes were identified in all cases; the first type exhibited positivity with anti-epithelial membrane antigen and anti-keratin antibodies, and the second type showed immunoreactivity with anti-keratin, anti-vimentin, and anti-neuron-specific enolase antibodies. Ultrastructural studies revealed bidirectional mucinous and neuroendocrine differentiation, demonstrated by the presence of two distinct cell types containing apically located mucous granules and basally concentrated neuroendocrine granules, respectively. The presence of neuroendocrine differentiation was supported by the immunohistochemical detection of vasoactive intestinal polypeptide in the tumor cells in one case and neuron-specific enolase in three cases. These findings suggest that the potential for mixed mucinous/neuroendocrine differentiation described in other endodermally derived tumors also exists in middle ear mucosa. We also believe that the rare lesions diagnosed as primary carcinoid tumors of the middle ear might in fact be MEA with predominant or only neuroendocrine differentiation. The clinical course of our four cases and our review of the pertinent literature confirm the benign nature of MEA and indicate that these tumors should be treated by complete local excision without additional therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

    2000-01-01

    in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions. Udgivelsesdato: 2000-Aug......, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present...... in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive...

  1. 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

    : Twenty-three newly-diagnosed CHF patients and 18 age- and gender-matched healthy subjects were exercised at two workloads, which were calculated to correspond to 50 and 75% of each individual's heart rate response. RESULTS: In CHF patients, baseline levels of ANP, BNP, AVP, PRA and ET-1 were elevated...... compared to healthy subjects. Exercise induced an increase in ANP, A and NA in both CHF patients and in normal subjects, however BNP was only increased in CHF patients and not in normal subjects. CONCLUSION: When CHF patients exercise at the same relative and submaximal level as age-matched healthy......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...

  2. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Jakobsen, Annika Loft;

    2010-01-01

    -eight prospectively enrolled patients with NE tumors underwent FDG-PET imaging. FDG uptake was quantified by maximal standardized uptake value (SUVmax). The prognostic value of FDG uptake, proliferation index, chromogranin A, and liver metastases were assessed. RESULTS: During the 1-year follow-up, 14 patients died......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...... was the only predictor of progression-free survival (HR, 8.4; P value of FDG-PET for NE tumors, which exceeds the prognostic value of traditional markers such as Ki67, chromogranin A, and liver metastases. FDG-PET may obtain an important role for NE...

  3. 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

  4. Neuroendocrine abnormalities in patients with traumatic brain injury

    Science.gov (United States)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    . Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

  5. Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

    2017-01-01

    Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

  6. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  7. 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.

  8. Treatment of congestive heart failure a neuroendocrine disorder.

    Science.gov (United States)

    Martin, M W S

    2003-04-01

    The understanding of heart failure is no longer based on a supply and demand model of pump failure. Rather, heart failure is seen as a complex pathophysiological process with activation of various neuroendocrine systems. The goals of treatment have changed towards modifying these counterproductive neuroendocrine systems and slowing myocardial maladaptation. Angiotensin converting enzyme inhibitors are the only licensed drugs in veterinary practice that have a direct effect on neurohormones in heart failure. The range of drug options in human medicine is greater and some of these drugs are also increasingly being used in veterinary cardiology practice. This review describes the neuroendocrine systems involved in heart failure and discusses the range of drugs available in human and veterinary medicine. In doing so, it concentrates on the evidence available from good quality randomised trials in both the veterinary field and, where relevant, the human medical field.

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

    Science.gov (United States)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark; Modlin, Irvin M

    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 pancreatic islet cells were first described in 1869 by Paul Langerhans. In 1924, Seale Harris was the first to describe endogenous hyperinsulinism/insulinoma. In 1942 William Becker and colleagues were the first to describe the glucagonoma syndrome. The first description of gastrinoma by Robert Zollinger and Edwin Ellison dates from 1955. The first description of the VIPoma syndrome by John Verner and Ashton Morrison dates from 1958. In 1977, the groups of Lars-Inge Larsson and Jens Rehfeld, and of Om Ganda reported the first cases of somatostatinoma. But only in 2013, Jens Rehfeld and colleagues described the CCK-oma syndrome. The most recently updated WHO classification for gastrointestinal neuroendocrine tumours dates from 2010.

  10. [Neuroendocrine pancreatic tumors and helpfulness of targeted therapies].

    Science.gov (United States)

    Vaysse, Thibaut; Coriat, Romain; Perkins, Géraldine; Dhooge, Marion; Brezault, Catherine; Chaussade, Stanislas

    2013-06-01

    The neuroendocrine pancreatic tumors are rare tumors, but their incidence is constantly rising. Even if the management of these tumors has to be surgical as soon as possible, the disease is most often metastatic at the stage of the diagnostic. The prognostic and the therapeutic options differ from pancreatic adenocarcinoma. Available treatments have evolved over the last years with recent publications of studies that bring to light the benefits of targeted therapies in this pathology. This has resulted in modifications of both practices and either French and international guidelines. Therefore, we focus on the management of the grade 1 and grade 2 well-differentiated neuroendocrine pancreatic tumors as classified in new WHO classification of neuroendocrine neoplasms published in 2010.

  11. Amantadine in the treatment of neuroendocrine side effects of neuroleptics.

    Science.gov (United States)

    Correa, N; Opler, L A; Kay, S R; Birmaher, B

    1987-04-01

    An open-label reversal drug study was undertaken on 10 neuroleptic-treated schizophrenic inpatients to assess the impact of amantadine hydrochloride on presumed prolactin-mediated neuroendocrine side effects. Measures were conducted across 7 weeks, including a 2-week neuroleptic baseline, a 3-week neuroleptic-plus-amantadine phase, and a 2-week return to the baseline regimen. Significant reduction with amantadine was observed on all six indices of neuroendocrine side effects: serum prolactin levels, body weight, gynecomastia/galactorrhea, breast tenderness, decreased libido, and amenorrhea. Improvement on these parameters was noted for as many as nine or all 10 patients, while in no cases was there worsening. In terms of motor and clinical effects, significant diminution of extrapyramidal and psycho-pathological symptoms was also achieved during this phase. The results suggested that amantadine may be beneficial for the treatment of neuro-endocrine side effects of antipsychotic medication owing to its ability to reverse neuroleptic-induced hyperprolactinemia.

  12. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

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

    Science.gov (United States)

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    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. PMID:25199978

  14. (SSR) markers

    African Journals Online (AJOL)

    SAM

    2014-07-30

    Jul 30, 2014 ... Simple sequence repeats (SSRs) are the most widely used marker system for plant variety characterization and ... gene tagging in marker assisted breeding and gene cloning in .... PLS-2 and PAU Selection Long) to 1.00 (between PC. 2062 and .... Comparative analyses of genetic diversities within tomato.

  15. (SSR) markers

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... seeded and black-seeded cultivars and breeding lines. The group B included 70 ... maize, rice and tomatoes (Reif et al., 2006; Vigouroux et al., 2005; Warburton et ..... development of molecular markers for marker-assisted breeding. .... Selection under domestication: evidence for a sweep in the rice Waxy ...

  16. Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Jacob Ø; Von Holstein, Sara Linea; Prause, Jan U;

    2014-01-01

    and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary...... hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma....

  17. Marker Detection in Aerial Images

    KAUST Repository

    Alharbi, Yazeed

    2017-04-09

    The problem that the thesis is trying to solve is the detection of small markers in high-resolution aerial images. Given a high-resolution image, the goal is to return the pixel coordinates corresponding to the center of the marker in the image. The marker has the shape of two triangles sharing a vertex in the middle, and it occupies no more than 0.01% of the image size. An improvement on the Histogram of Oriented Gradients (HOG) is proposed, eliminating the majority of baseline HOG false positives for marker detection. The improvement is guided by the observation that standard HOG description struggles to separate markers from negatives patches containing an X shape. The proposed method alters intensities with the aim of altering gradients. The intensity-dependent gradient alteration leads to more separation between filled and unfilled shapes. The improvement is used in a two-stage algorithm to achieve high recall and high precision in detection of markers in aerial images. In the first stage, two classifiers are used: one to quickly eliminate most of the uninteresting parts of the image, and one to carefully select the marker among the remaining interesting regions. Interesting regions are selected by scanning the image with a fast classifier trained on the HOG features of markers in all rotations and scales. The next classifier is more precise and uses our method to eliminate the majority of the false positives of standard HOG. In the second stage, detected markers are tracked forward and backward in time. Tracking is needed to detect extremely blurred or distorted markers that are missed by the previous stage. The algorithm achieves 94% recall with minimal user guidance. An average of 30 guesses are given per image; the user verifies for each whether it is a marker or not. The brute force approach would return 100,000 guesses per image.

  18. 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...

  19. Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

    OpenAIRE

    2008-01-01

    Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, t...

  20. Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management.

    Science.gov (United States)

    Sahani, Dushyant V; Bonaffini, Pietro A; Fernández-Del Castillo, Carlos; Blake, Michael A

    2013-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and are characterized by a wide spectrum of clinical manifestations. All NETs are potentially malignant but differ in their biologic characteristics and the probability of metastatic disease. The pathologic classification of these tumors relies on their proliferation and differentiation. In the past decades, several nomenclatures have been proposed to stratify neuroendocrine tumors, but the World Health Organization classification is the one that is most widely accepted and used. The diagnosis of neuroendocrine tumor relies on clinical manifestation, laboratory parameters, imaging features, and tissue biomarkers in a biopsy specimen. With improved understanding of the natural history and lesion biology, management of GEP-NETs has also evolved. Although surgery remains the only potentially curative therapy for patients with primary GEP-NETs, other available treatments include chemotherapy, interferon, somatostatin analogs, and targeted therapies. Recent improvements in both morphologic and functional imaging methods have contributed immensely to patient care. Morphologic imaging with contrast agent-enhanced multidetector computed tomography and magnetic resonance imaging is most widely used for initial evaluation and staging of disease in these patients, whereas functional imaging techniques are useful both for detection and prognostic evaluation and can change treatment planning.

  1. A retroperitoneal neuroendocrine tumor in ectopic pancreatic tissue.

    Science.gov (United States)

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-07-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor.

  2. 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.

  3. Composite neuroendocrine and adenomatous carcinoma of the papilla of Vater

    Institute of Scientific and Technical Information of China (English)

    Joanna A Musialik; Maciej J Kohut; Tomasz Marek; Anatol Wodo(I)a(z)ski; Marek Hartleb

    2009-01-01

    Malignant tumors of papilla are usually adenocarcinomas.We present a 67-year-old female who became icteric as result of a malignant tumor infiltrating the papilla of Vater. Histopathological assessment of surgically excised tumor showed both neuroendocrine and adenocarcinomatous features. To our knowledge, this is the seventh report of this rare neoplastic association in the duodenal periampullary region.

  4. [Neuroendocrine features of prostatic tumors: state of the art].

    Science.gov (United States)

    Turitto, Giacinto; Frattolillo, Adele; Iodice, Patrizia; Auriemma, Annunziata; Tortoriello, Annamaria; di Grazia, Maria; Iaffaioli, Rosario Vincenzo

    2003-12-01

    Neuroendocrine (NE) differentiation in prostate cancer has received much attention recently because it has been found to be associated with androgen independence and shortened patient survival in some studies. The present review focuses on morphogenics origins of NE cells, growth properties and the androgen receptor status and relationship between NE-secreted products and regulation of angiogenesis and apoptosis.

  5. 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.

  6. 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.)

  7. Neuroendocrine actions of organohalogens: thyroid hormones, arginine vasopressin, and neuroplasticity.

    Science.gov (United States)

    Kodavanti, Prasada Rao S; Curras-Collazo, Margarita C

    2010-10-01

    Organohalogen compounds are global environmental pollutants. They are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be a significant source of human exposure, especially for children. One significant concern with regard to health effects associated with exposure to organohalogens is endocrine disruption. This review focuses on PCBs and PBDEs as old and new organohalogens, respectively, and their effects on two neuroendocrine systems; thyroid hormones and the arginine vasopressin system (AVP). Regarding neuroendocrine effects of organohalogens, there is considerable information on the thyroid system as a target and evidence is now accumulating that the AVP system and associated functions are also susceptible to disruption. AVP-mediated functions such as osmoregulation, cardiovascular function as well as social behavior, sexual function and learning/memory are discussed. For both thyroid and AVP systems, the timing of exposure seems to play a major role in the outcome of adverse effects. The mechanism of organohalogen action is well understood for the thyroid system. In comparison, this aspect is understudied in the AVP system but some similarities in neural processes, shown to be targeted by these pollutants, serve as promising possibilities for study. One challenge in understanding modes of action within neuroendocrine systems is their complexity stemming, in part, from interdependent levels of organization. Further, because of the interplay between neuroendocrine and neural functions and behavior, further investigation into organohalogen-mediated effects is warranted and may yield insights with wider scope. Indeed, the current literature provides scattered evidence regarding the role of organohalogen-induced neuroendocrine disruption in the neuroplasticity related to both learning functions and brain

  8. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  9. 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.

  10. Neuroendocrine tumors (carcinoids of the stomach and intestines - early diagnosis and minimally invasive endoscopic procedures

    Directory of Open Access Journals (Sweden)

    Kuryk O.G.

    2014-03-01

    Full Text Available Background. Neuroendocrine tumors of the stomach and intestines are rare diseases. Increasing incidence and complexity of diagnosis of these diseases cause acuteness of the problem. Objective. To evaluate the effectiveness of morphological examination of endoscopic biopsy material for diagnostics of neuroendocrine tumors and for evaluation of completeness of minimally invasive endoscopic surgical interventions (endoscopic mucosal resection and endoscopic submucosal dissection at neuroendocrine tumors. Methods. On the basis of Medical center "Oberig" in 2009 - 2013 in eight cases neuroendocrine tumors were diagnosed: 2 (25 % in the stomach, 2 (25% – in the duodenum, 2 (25% - in the small intestine, 1 (12.5 % - in the ascending colon, 1 (12.5% - in the rectum. Neuroendocrine tumors of stomach and ileum were removed by endoscopic mucosal resection, duodenal bulb and rectum neuroendocrine tumors – by endoscopic submucosal dissection, papillary duodenum, colon and jejunum neuroendocrine tumors – by surgical resection. Results. It was shown, that morphological evaluation of endoscopic mucosal biopsies is effective way to diagnose the neuroendocrine tumors. Conclusion. Endoscopic mucosal resection and endoscopic submucosal dissection allows to get advanced material for morphological diagnosis of neuroendocrine tumors and an adequate method of their removing Citation: Kuryk OG, Yakovenko VO, Bazdyrev VV, Bodnar LV. [Neuroendocrine tumors (carcinoids of the stomach and intestines - early diagnosis and minimally invasive endoscopic procedures]. Morphologia. 2014;8(1:58-64. Ukrainian.

  11. Human achaete-scute homolog-1 expression in neuroendocrine breast carcinoma.

    Science.gov (United States)

    Righi, Luisella; Rapa, Ida; Votta, Arianna; Papotti, Mauro; Sapino, Anna

    2012-04-01

    Neuroendocrine (NE) breast carcinoma is defined by morphological features similar to those of NE tumors of other organs and NE marker expression in at least 50 % of neoplastic cells. However, a NE morphology may be observed even in breast carcinomas lacking NE markers. Human achaete-scute homolog-1 (hASH-1) is a transcription factor that plays a key role in the regulation of mammalian neural and NE cell development and has been identified in several human NE tumors. The aim of this study was to investigate hASH-1 expression in human breast cancers. hASH-1 expression was evaluated in 482 consecutive non-NE invasive breast carcinomas, in a series of 84 breast cancers with >50 % NE marker expression (high NE differentiation) and 21 carcinomas with NE histology but negative or focally (<50 %) positive for NE markers (low NE differentiation). hASH-1 protein was evaluated by a specific monoclonal antibody using immunohistochemistry and gene expression by real-time polymerase chain reaction. None of the non-NE invasive breast carcinomas expressed hASH-1 at any levels. hASH-1 was expressed in tumor cell nuclei of 63 and 38 % of cases with high and low NE differentiation, respectively. Strong correlation with protein and gene expression levels was observed (p < 0.0001). hASH-1 expression was correlated to a low mitotic count (p = 0.02) and a low Ki67 proliferative index (p = 0.0062). hASH-1 expression occurs in breast cancers with NE differentiation regardless of the extent of the NE cell population, and it is restricted to a subset of tumor cells having a low proliferative potential.

  12. Localization of integral membrane peptidylglycine alpha-amidating monooxygenase in neuroendocrine cells.

    Science.gov (United States)

    Milgram, S L; Kho, S T; Martin, G V; Mains, R E; Eipper, B A

    1997-03-01

    Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the amidation of glycine-extended peptides in neuroendocrine cells. At steady state, membrane PAM is accumulated in a perinuclear compartment. We examined the distribution of membrane PAM in stably transfected AtT-20 cells and compared its localization to markers for the trans-Golgi network (TGN), endosomes, and lysosomes. At the light microscopic level, the distribution of membrane PAM does not overlap extensively with lysosomal markers but does overlap with TGN38 and with SCAMP, a component of post-Golgi membranes involved in recycling pathways. By immunoelectron microscopy, membrane PAM is present in tubulovesicular structures which constitute the TGN; some of these PAM-containing tubulovesicular structures are more distal to the Golgi stacks and do not contain TGN38. While some POMC-derived peptides are present in tubulovesicular structures like those that contain membrane PAM, the majority of the POMC-derived peptides are present in secretory granules. There is little overlap between the steady state distribution of membrane PAM and internalized FITC-transferrin in the early endosomes. Few of the perinuclear PAM-containing structures are labeled with HRP or WGA-HRP even following long incubations. Therefore, membrane PAM is localized to perinuclear tubulovesicular structures which are partially devoid of TGN38 and are not all endosomal in origin.

  13. Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling.

    Science.gov (United States)

    O'Neill, Casey E; Newsom, Ryan J; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C; Spencer, Robert L; Campeau, Serge; Bachtell, Ryan K

    2016-05-01

    Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased

  14. Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Aakhus Svend

    2010-01-01

    Full Text Available Abstract Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2 is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3. Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR. Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3. There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.

  15. Child maltreatment, inflammation, and internalizing symptoms: Investigating the roles of C-reactive protein, gene variation, and neuroendocrine regulation.

    Science.gov (United States)

    Cicchetti, Dante; Handley, Elizabeth D; Rogosch, Fred A

    2015-05-01

    Prior research has found inconsistent evidence regarding the association among childhood adversity, inflammation, and internalizing symptoms, perhaps because previous studies have yet to adequately integrate important factors such as the timing of the adversity, genetic variation, and other relevant processes such as neuroendocrine regulation. The aims of the present study were threefold: (a) to determine whether the effect of the timing of child maltreatment on C-reactive protein (CRP), an inflammatory marker, varies by CRP gene variation; (b) to explore whether links between salivary CRP and childhood internalizing symptoms depend on the presence and timing of maltreatment experiences; and (c) to investigate the role of CRP in the relations between child neuroendocrine regulation and internalizing symptoms and examine whether these associations are moderated by the presence and timing of child maltreatment. Participants included a sample of 267 maltreated and 222 nonmaltreated children (M age = 9.72, SD = 0.99; 52.4% male; 66% African American) who attended a summer day camp research program designed for school-aged low-income children. Department of Human Services records were examined to determine the onset and recency of maltreatment for children in the maltreated group. The results indicated that among children with recent onset maltreatment, those with at least one A allele from CRP single nucleotide polymorphism rs1417938 evidenced significantly higher CRP levels compared to recently maltreated children carrying the TT genotype. Moreover, higher levels of CRP were associated with higher levels of internalizing symptoms only for recently maltreated children. Finally, we did not find support for salivary CRP as a mechanism in the relation between neuroendocrine regulation and childhood internalizing symptoms. Our findings highlight the importance of the timing of child maltreatment and have important implications for characterizing variability in inflammation

  16. Targeted Agents in Treatment of Neuroendocrine Tumors of Pancreas

    Directory of Open Access Journals (Sweden)

    Ilias N Karampelas

    2014-07-01

    Full Text Available Neuroendocrine tumors (NET of the pancreas are uncommon neoplasms that arise from the pancreatic islet cells. Surgical resections are being tested, as well as multiple chemotherapy agents. Current treatment options for nonresectable disease include somatostatin analogs and chemotherapy. New therapies focus on specific molecular targets such as sunitinib, angiogenesis inhibitor, that target vascular endothelial growth factor receptor (VEGFR and other growth factor receptors and everolimus, an inhibitor of the mammalian target of rapamycin. Functionally based medical therapies for NET include somatostatin analogs to control symptoms. The 2014 annual meeting of American Society of Clinical Oncology (ASCO brought us new insights into the management of pancreatic neuroendocrine tumors. The focus of this review will serve to highlight specific Abstracts (#e15160 and #e15161, that shed light on new therapeutic options that help target the unique pathways of this malignancies.

  17. [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.

  18. A feline case of hepatic neuroendocrine carcinoma with gastrin immunoreactivity.

    Science.gov (United States)

    Kita, Chiaki; Yamagami, Tetsushi; Kinouchi, Shigemi; Nakano, Masayuki; Nagata, Nao; Suzuki, Hitomi; Ohtake, Yuzo; Miyoshi, Takuma; Irie, Mitsuhiro; Uchida, Kazuyuki

    2014-06-01

    A 5-year-old castrated Japanese domestic cat was presented with persistent vomiting. Ultrasound examinations revealed many masses only in the liver, and the fine needle aspiration was performed. Cytologically, polygonal or oval shaped tumor cells forming rosette and cord-like patterns were demonstrated, and then, the hepatic lesions were diagnosed as neuroendocrine carcinoma tentatively. The cat died one month after admission and was necropsied. Histopathologically, the tumor cells of the hepatic mass were arranged in typical rosette and cord-like structures. They were considerably uniform in size with hyperchromatic round nuclei and eosinophilic cytoplasm. Most of tumor cells were immunopositive for chromogranin A, and some were positive for gastrin. The findings indicate the possibility that the present case was a gastrin-producing neuroendocrine carcinoma.

  19. 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.

  20. Paranasal Sinus Neuroendocrine Carcinoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nagesh T. Sirsath

    2013-01-01

    Full Text Available Neuroendocrine neoplasms are defined as epithelial neoplasms with predominant neuroendocrine differentiation. They can arise in almost every organ of the body although they are most commonly found in the gastrointestinal tract and respiratory system. Nasal cavity and paranasal sinuses are a rare site for neuroendocrine carcinoma. In contrast to the other regions, neuroendocrine tumours of the sinuses have been reported to be recurrent and locally destructive. Very few cases of paranasal sinus neuroendocrine carcinoma have been reported till date. Difficulty in pathologic diagnosis and rarity of this malignancy have hindered the progress in understanding the clinical course and improving outcomes. We herein report a case of poorly differentiated neuroendocrine tumour of ethmoid and sphenoid sinus with invasion of orbit and intracranial extension. The patient had complete response at the end of chemoradiation and he was disease-free for 9 months duration after which he developed bone metastasis without regional recurrence.

  1. 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.

  2. 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.

  3. 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

  4. [Biotherapy of neuroendocrine tumours of the gastrointestinal tract and pancreas

    DEFF Research Database (Denmark)

    Hansen, C.P.; Knigge, U.

    2008-01-01

    Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth...... is less convincing although a stabilization of disease is recorded in almost 50% of patients. Interferon treatment should mainly be considered for tumours with a low proliferation index Udgivelsesdato: 2008/6/9...

  5. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report

    OpenAIRE

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    Patient: Male, 71 Final Diagnosis: Neuroendocrine cancer bladder Symptoms: Dysuria • haematuria Medication: — Clinical Procedure: Transurethral resection of the bladder tumor Specialty: Oncology Objective: Rare disease Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, sho...

  6. Cystic pancreatic neuroendocrine tumors: To date a diagnostic challenge.

    Science.gov (United States)

    Caglià, Pietro; Cannizzaro, Maria Teresa; Tracia, Angelo; Amodeo, Luca; Tracia, Luciano; Buffone, Antonino; Amodeo, Corrado; Cannizzaro, Matteo Angelo

    2015-09-01

    Cystic PNETs are an uncommon neoplasms increasingly detected in current clinical practice which often present a diagnostic challenges to both the experienced radiologist and pathologist. The aim of this study was to review the available literature to summarize current data that compare and evaluate both the clinical and pathologic features of cystic pancreatic neuroendocrine tumors. A systematic review of the current literature was performed using the search engines EMBASE and PubMed to identify all studies reporting on cystic pancreatic neuroendocrine tumors. The MeSH search terms used were "cystic pancreatic neuroendocrine tumors", "endocrine neoplasms", and "pancreatic cysts". Multiple combinations of the keywords and MeSH terms were used. The clinical evaluation of cystic pancreatic lesions appears to suffer from same limitations despite the improvement in the diagnostic tools. Subsequently, we highlight diagnostic pitfalls and differential diagnosis of these cystic tumors. In this review we discuss current advances in the application of the imaging modalities and characteristics features with special emphasize on endoscopic ultrasound (EUS), and EUS guide fine needle aspiration (EUS-FNA). Cystic neuroendocrine tumor in the pancreas underlines the clinical impact of endoscopic ultrasound in the work-up of patients with unclear lesions in the pancreas. EUS-FNA cytology and cyst fluid analysis is a useful adjunct to abdominal imaging for the diagnosis of pancreatic cystic lesions. Due to the evident diagnostic difficulties, we hypothesize that cyst fluid characteristics, including cytomorphological features, is the most accurate test to achieve a preoperative diagnosis and to provide a basis for prognostic prediction. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  7. Lanreotide Depot: An Antineoplastic Treatment of Carcinoid or Neuroendocrine Tumors

    OpenAIRE

    Wolin, Edward M.; Manon, Amandine; Chassaing, Christophe; Lewis, Andy; Bertocchi, Laurent; Richard,Joel; Phan,Alexandria T

    2016-01-01

    Purpose Peptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europ...

  8. Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Ritter, J M; Garner, M M; Chilton, J A; Jacobson, E R; Kiupel, M

    2009-11-01

    This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.

  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. 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.

  11. Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors

    OpenAIRE

    Sherman, Scott K.; Maxwell, Jessica E.; Carr, Jennifer C.; Wang, Donghong; Bellizzi, Andrew M.; O’Dorisio, M. Sue; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs. This study sought to determine expression differences of four genes in neuroendocrine metastases and to create a gene expression algorithm to distinguish the primary site. No...

  12. Low ambient temperature and neuroendocrine response to hypoglycemia in men.

    Science.gov (United States)

    Jezová, D; Juránková, E; Kvetnanský, R; Kaciuba-Uscilko, H; Nazar, K; Vigas, M

    1995-12-01

    Nutritional factors, such as an excess or a deficiency of glucose, play an important role in neuroendocrine regulations. Hormonal and metabolic responses to hypoglycemia were examined in healthy non-obese volunteers under conditions of low ambient temperature. Hypoglycemia was induced by intravenous injection of insulin in two randomized trials performed at room temperature and at 4 degrees C. At room temperature, the typical neuroendocrine response to hypoglycemia was established. The increases of ACTH, beta-endorphin, growth hormone and cortisol in response to insulin hypoglycemia failed to be modified by low ambient temperature. Acute cold exposure significantly reduced epinephrine and totally inhibited prolactin response to insulin-induced hypoglycemia. In spite of significant changes in epinephrine response to hypoglycemia at low ambient temperature, no striking differences in plasma glucose levels compared to those measured at room temperature were observed. However, under conditions of low temperature the reestablishment of normoglycemia was delayed. No changes in free fatty acids were found under our experimental conditions. The presented data show that low ambient temperature exerts selective effects on some neuroendocrine and metabolic parameters.

  13. 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.

  14. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Helga Bertani

    2011-01-01

    Full Text Available 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.

  15. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

    Science.gov (United States)

    Ofikwu, Godwin; Mani, Vishnu R.; Rajabalan, Ajai; Adu, Albert; Ahmed, Leaque; Vega, Dennis

    2015-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs) which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linear proliferation. It is usually seen in middle-aged, nonsmoking women with symptoms of cough, dyspnea, and wheezing. We present a 45-year-old, nonsmoking woman who presented with symptoms of DIPNECH associated with bilateral pulmonary nodules and left hilar adenopathy. Of interest, DIPNECH in our patient was associated with metastatic pulmonary carcinoids, papillary carcinoma of the left breast, oncocytoma and angiomyolipoma of her left kidney, and cortical nodules suggestive of tuberous sclerosis. She had video assisted thoracoscopic surgery (VATS), modified radical mastectomy with reconstruction, and radical nephrectomy. She is currently symptom-free most of the time with over two years of follow-up. PMID:26609460

  16. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

    Directory of Open Access Journals (Sweden)

    Godwin Ofikwu

    2015-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linear proliferation. It is usually seen in middle-aged, nonsmoking women with symptoms of cough, dyspnea, and wheezing. We present a 45-year-old, nonsmoking woman who presented with symptoms of DIPNECH associated with bilateral pulmonary nodules and left hilar adenopathy. Of interest, DIPNECH in our patient was associated with metastatic pulmonary carcinoids, papillary carcinoma of the left breast, oncocytoma and angiomyolipoma of her left kidney, and cortical nodules suggestive of tuberous sclerosis. She had video assisted thoracoscopic surgery (VATS, modified radical mastectomy with reconstruction, and radical nephrectomy. She is currently symptom-free most of the time with over two years of follow-up.

  17. Rectal neuroendocrine tumor with uncommon metastaticspread: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Neuroendocrine tumors of the gastrointestinal tract arerare neoplasms. Rectal neuroendocrine tumors consistapproximately the 5%-14% of all neuroendocrine neoplasmsin Europe. These tumors are diagnosed in relativelyyoung patients, with a mean age at diagnosis of 56years. Distant metastases from rectal neuroendocrinetumors are not very common. Herein we describe a caseof a rectal neuroendocrine tumor which metastasized tothe lung, mediastinum and orbit. This case underscoresthe importance of early identification and optimalmanagement to improve patient's prognosis. Therefore,the clinical significance of this case is the necessityof physicians' awareness and education regardingneuroendocrine tumors' diagnosis and management.

  18. Four cases of large cell neuroendocrine carcinoma of the stomach: findings on CT and barium studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Jung; Choi, Dong Il; Lee, Soon Jin; Lee, Won Jae; Kim, Sung; Kim, Jae J.; Park, Cheol Keun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2008-06-15

    A large cell neuroendocrine carcinoma of the stomach is extremely rare. We have reviewed the medical records and imaging studies of the four patients that presented with a large cell neuroendocrine carcinomas of the stomach. On a barium study and CT imaging, a gastric large cell neuroendocrine carcinoma is depicted as an ulcerofungating tumor with minimal peritumoral infiltration and metastatic lymphadenopathy in the perigastric area. These findings are similar to findings for advanced gastric cancer, especially Borrmann type II. However, a gastric large cell neuroendocrine carcinoma is highly malignant with a significantly worse prognosis than a usual adenocarcinoma.

  19. The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer.

    Science.gov (United States)

    Bishop, Jennifer L; Thaper, Daksh; Vahid, Sepideh; Davies, Alastair; Ketola, Kirsi; Kuruma, Hidetoshi; Jama, Randy; Nip, Ka Mun; Angeles, Arkhjamil; Johnson, Fraser; Wyatt, Alexander W; Fazli, Ladan; Gleave, Martin E; Lin, Dong; Rubin, Mark A; Collins, Colin C; Wang, Yuzhuo; Beltran, Himisha; Zoubeidi, Amina

    2017-01-01

    Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor-resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo Mechanistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2. Underscoring its inverse correlation with classic AR activity in clinical samples, BRN2 expression was highest in NEPC tumors and was significantly increased in castration-resistant prostate cancer compared with adenocarcinoma, especially in patients with low serum PSA. These data reveal a novel mechanism of AR-dependent control of NEPC and suggest that targeting BRN2 is a strategy to treat or prevent neuroendocrine differentiation in prostate tumors.

  20. Neuroendocrine markers of high risk for psychosis : salivary testosterone in adolescent boys with prodromal symptoms

    NARCIS (Netherlands)

    van Rijn, S.; Aleman, A.; de Sonneville, L.; Sprong, M.; Ziermans, T.; Schothorst, P.; van Engeland, H.; Swaab, H.

    2011-01-01

    Background. The peak in age of onset of psychotic disorders such as schizophrenia during puberty and early adulthood suggests a relationship between the expression of psychopathology and the changes in the brain and body that take place during this dynamic maturational period, including a dramatic i

  1. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Barbara Seroczyńska

    2013-10-01

    Full Text Available Neuroendocrine tumors (NETs are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL−1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1–300 ng mL−1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  2. Chemometric evaluation of urinary steroid hormone levels as potential biomarkers of neuroendocrine tumors.

    Science.gov (United States)

    Plenis, Alina; Miękus, Natalia; Olędzka, Ilona; Bączek, Tomasz; Lewczuk, Anna; Woźniak, Zofia; Koszałka, Patrycja; Seroczyńska, Barbara; Skokowski, Jarosław

    2013-10-16

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  3. Epithelial-Mesenchymal Transition Is a Critical Step in Tumorgenesis of Pancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fendrich, Volker, E-mail: fendrich@med.uni-marburg.de; Maschuw, Katja; Waldmann, Jens [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Buchholz, Malte [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Rehm, Johannes [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Gress, Thomas M. [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Bartsch, Detlef K. [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); König, Alexander [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany)

    2012-03-08

    The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.

  4. Epithelial-Mesenchymal Transition Is a Critical Step in Tumorgenesis of Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Alexander König

    2012-03-01

    Full Text Available The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT, a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.

  5. Neuroendocrine and behavioral effects of embryonic exposure to endocrine disrupting chemicals in birds.

    Science.gov (United States)

    Ottinger, Mary Ann; Lavoie, Emma; Thompson, Nichola; Barton, Ashley; Whitehouse, Kasen; Barton, Meredith; Abdelnabi, Mahmoud; Quinn, Michael; Panzica, GianCarlo; Viglietti-Panzica, Carla

    2008-03-01

    Endocrine disrupting chemicals (EDCs) exert hormone-like activity in vertebrates and exposure to these compounds may induce both short- and long-term deleterious effects including functional alterations that contribute to decreased reproduction and fitness. An overview of the effects of a number of EDCs, including androgenic and estrogenic compounds, will be considered. Many studies have been conducted in the precocial Japanese quail, which provides an excellent avian model for testing these compounds. Long-term impacts have also been studied by raising a subset of animals through maturation. The EDCs examined included estradiol, androgen active compounds, soy phytoestrogens, and atrazine. Effects on behavior and hypothalamic neuroendocrine systems were examined. All EDCs impaired reproduction, regardless of potential mechanism of action. Male sexual behavior proved to be a sensitive index of EDC exposure and embryonic exposure to a variety of EDCs consistently resulted in impaired male sexual behavior. Several hypothalamic neural systems proved to be EDC responsive, including arginine vasotocin (VT), catecholamines, and gonadotropin releasing hormone system (GnRH-I). Finally, EDCs are known to impact both the immune and thyroid systems; these effects are significant for assessing the overall impact of EDCs on the fitness of avian populations. Therefore, exposure to EDCs during embryonic development has consequences beyond impaired function of the reproductive axis. In conclusion, behavioral alterations have the advantage of revealing both direct and indirect effects of exposure to an EDC and in some cases can provide a valuable clue into functional deficits at different physiological levels.

  6. 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.

  7. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.

    Science.gov (United States)

    Pryor, Jennifer G; Simon, Rochelle A; Bourne, Patricia A; Spaulding, Betsy O; Scott, Glynis A; Xu, Haodong

    2009-02-01

    -grade neuroendocrine carcinomas, irrespective of anatomical location, and a potential marker to predict metastatic disease.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 6-L-(18)F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors : Basic aspects and emerging clinical applications

    NARCIS (Netherlands)

    Jager, Pieter L.; Chirakal, Raman; Marriott, Christopher J.; Brouwers, Adrienne H.; Koopmans, Klaas Pieter; Gulenchyn, Karen Y.

    2008-01-01

    In recent years, 6-L-(18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the upt

  12. 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....

  13. Neuroendocrine reactivity and recovery from work with different physical and mental demands

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF; Heisterkamp, SH

    2000-01-01

    Objectives The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. Methods Neuroendocrine reactivity and recovery wer

  14. Aberrant Menin expression is an early event in pancreatic neuroendocrine tumorigenesis

    NARCIS (Netherlands)

    Hackeng, Wenzel M.; Brosens, Lodewijk A A; Poruk, Katherine E.; Noë, Michaël; Hosoda, Waki; Poling, Justin S.; Rizzo, Anthony; Campbell-Thompson, Martha; Atkinson, Mark A.; Konukiewitz, Björn; Klöppel, Günter; Heaphy, Christopher M.; Meeker, Alan K.; Wood, Laura D.

    2016-01-01

    Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic malignancy and cause significant morbidity and mortality. Neuroendocrine microadenomas have been proposed as a potential precursor lesion for sporadic PanNETs. In this study, we applied telomere-specific fluorescent in

  15. Marker Recycling in Candida albicans through CRISPR-Cas9-Induced Marker Excision

    Science.gov (United States)

    2017-01-01

    ABSTRACT We describe here a new approach to marker recycling, a controlled sequence of steps in which a genetic marker is selected and then lost. Marker recycling is important for genetic manipulation, because it allows a single selection marker to be used repeatedly. Our approach relies upon the ability of the CRISPR-Cas9 system to make a targeted double-strand break in DNA and the expectation that a double-strand break within a selection marker may promote recombination between directly repeated sequences that flank the marker. We call the approach CRISPR-Cas9-induced marker excision (CRIME). We tested the utility of this approach with the fungal pathogen Candida albicans, which is typically diploid. We used two selection markers, modified to include flanking direct repeats. In a proof-of-principle study, we created successive homozygous deletions in three genes through use of the two markers and had one of the markers available in the final strain for further selection and recycling. This strategy will accelerate the creation of multiple-mutant strains in C. albicans. CRISPR-Cas9 systems have been applied to many organisms, so the genetic design principles described here may be broadly applicable. IMPORTANCE It is critical to be able to alter genes in order to elucidate their functions. These alterations often rely upon markers that allow selection for a rare cell in a population that has incorporated a piece of DNA. The number of alterations that can be accomplished is thus limited by the number of selection markers that are available. This limitation is circumvented by marker recycling strategies, in which a marker is eliminated after its initial use. Then, the marker can be used again. In this report, we describe a new marker recycling strategy that is enabled by recently developed CRISPR-Cas9 technology. PMID:28317025

  16. Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes

    Science.gov (United States)

    Neumann, I D; Johnstone, H A; Hatzinger, M; Liebsch, G; Shipston, M; Russell, J A; Landgraf, R; Douglas, A J

    1998-01-01

    The responsiveness of the rat hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-neurohypophysial system (HNS) to emotional (elevated plus-maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin-releasing hormone (CRH) was investigated during pregnancy and lactation. In addition to pregnancy-related adaptations at the adenohypophysial level, behavioural responses accompanying the neuroendocrine changes were studied. Whereas basal (a.m.) plasma corticosterone, but not corticotrophin (adrenocorticotrophic hormone; ACTH), levels were increased on the last day (i.e. on day 22) of pregnancy, the stress-induced rise in both plasma hormone concentrations was increasingly attenuated with the progression of pregnancy beginning on day 15 and reaching a minimum on day 21 compared with virgin control rats. A similar attenuation of responses to both emotional and physical stressors was found in lactating rats. Although the basal plasma oxytocin concentration was elevated in late pregnancy, the stress-induced rise in oxytocin secretion was slightly lower in day 21 pregnant rats. In contrast to vasopressin, oxytocin secretion was increased by forced swimming in virgin and early pregnant rats indicating a differential stress response of these neurohypophysial hormones. The blunted HPA response to stressful stimuli is partly due to alterations at the level of corticotrophs in the adenohypophysis, as ACTH secretion in response to CRH in vivo (40 ng kg−1, i.v.) was reduced with the progression of pregnancy and during lactation. In vitro measurement of cAMP levels in pituitary segments demonstrated reduced basal levels of cAMP and a lower increase after CRH stimulation (10 nm, 10 min) in day 21 pregnant compared with virgin rats, further indicating reduced corticotroph responsiveness to CRH in pregnancy. The reduced pituitary response to CRH in late pregnancy is likely to be a consequence of a reduction in CRH receptor binding as

  17. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants

    Science.gov (United States)

    de Andrade, Camila Alves; Oliveira, Katherine Simone Caires; Tossige-Gomes, Rosalina; Rocha-Vieira, Etel; Neves, Camila Danielle Cunha; Vieira, Érica Leandro Marciano; Leite, Hércules Ribeiro; Oliveira, Murilo Xavier; Júnior, Antônio Lúcio Teixeira; Coimbra, Cândido Celso

    2016-01-01

    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. PMID:27907172

  18. Mediators of compassionate goal intervention effects on human neuroendocrine responses to the Trier Social Stress Test.

    Science.gov (United States)

    Erickson, Thane M; Mayer, Stefanie E; Lopez-Duran, Nestor L; Scarsella, Gina M; McGuire, Adam P; Crocker, Jennifer; Abelson, James L

    2017-08-28

    The hypothalamic-pituitary-adrenal (HPA) axis is thought to mediate the effects of stress on illness. Research has identified a limited number of psychological variables that modulate human HPA responses to stressors (e.g. perceived control and social support). Prosocial goals can reduce subjective stress, but have not been carefully examined in experimental settings where pathways of impact on biological stress markers may be traced. Recent work demonstrated that coaching individuals to strive to help others reduced HPA responses to the Trier Social Stress Test (TSST) relative to other cognitive interventions. However, identification of mediational pathways, which were not examined in the original study, is necessary to determine whether the HPA buffering effects were due to helping motivations (compassionate goals; CGs) rather than via previously identified variables such as control or support. In this new analysis, we combined the original cortisol data with novel observer ratings of interpersonal behavior and psychological variables during the stress task, and conducted new, theory-driven analyses to determine psychological mediators for the intervention's effect on cortisol responses (N = 54; 21 females, 33 males; 486 cortisol samples). Control, support, and task ego-threat failed to account for the effects of the intervention. As hypothesized, self and observer-rated CGs, as well as observer-rated perceptions of participants' interpersonal behavior as morally desirable (but not as dominant or affiliative) were significant mediators of neuroendocrine responses. The findings suggest that stress-reduction interventions based on prosocial behavior should target particular motivational and interpersonal features.

  19. Neuroendocrine and behavioral responses to weak electric fields in adult sea lampreys (Petromyzon marinus).

    Science.gov (United States)

    Chung-Davidson, Yu-Wen; Bryan, Mara B; Teeter, John; Bedore, Christine N; Li, Weiming

    2008-06-01

    We characterized the behavioral and neuroendocrine responses of adult sea lampreys (Petromyzon marinus) to weak electric fields. Adult sea lampreys, captured during upstream spawning migration, exhibited limited active behaviors during exposure to weak electric fields and spent the most time attached to the wall of the testing arena near the cathode (-). For adult male sea lampreys, exposure to weak electric fields resulted in increased lamprey (l) GnRH-I mRNA expression but decreased lGnRH-I immunoreactivities in the forebrain, and decreased Jun (a neuronal activation marker) mRNA levels in the brain stem. Similar effects were not observed in the brains of female sea lampreys after weak electric field stimulation. The influence of electroreception on forebrain lGnRH suggests that electroreception may modulate the reproductive systems in adult male sea lampreys. The changes in Jun expression may be associated with swimming inhibition during weak electric field stimulation. The results for adult sea lampreys are the opposite of those obtained using parasitic-stage sea lampreys, which displayed increased activity during and after cathodal stimulation. Our results demonstrate that adult sea lampreys are sensitive to weak electric fields, which may play a role in reproduction. They also suggest that electrical stimuli mediate different behaviors in feeding-stage and spawning-stage sea lampreys.

  20. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

    Science.gov (United States)

    Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

    2013-09-01

    Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

  1. Clinical utility of lanreotide Autogel(®) in gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Paragliola, Rosa Maria; Prete, Alessandro; Papi, Giampaolo; Torino, Francesco; Corsello, Andrea; Pontecorvi, Alfredo; Corsello, Salvatore Maria

    2016-01-01

    Somatostatin analogs (SSAs), which were initially used to control hormonal syndromes associated with neuroendocrine neoplasms (NENs), have been successfully proposed as antiproliferative agents, able to control tumor growth in patients affected by gastroenteropancreatic (GEP)-NENs. The development of long-acting formulations of SSAs which require only weekly or monthly injections can improve patient compliance. In particular, lanreotide (LAN) Autogel(®), which is a viscous aqueous formulation supplied in ready-to-use prefilled syringes, can be administered every 28-56 days. Since its introduction in the clinical practice, several studies evaluated the clinical utility of LAN Autogel in the medical treatment of GEP-NENs. Although there is no evidence of an overall survival benefit, these studies confirm the efficacy of LAN Autogel in terms of benefit in progression-free survival, and in more than half of cases, a reduction of tumor markers can be observed during treatment with this drug. Moreover, LAN Autogel is widely recognized to be effective in controlling tumor-related symptoms in the majority of patients affected by GEP tumors, especially in patients affected by carcinoid syndrome, improving considerably patients' quality of life.

  2. Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

    Science.gov (United States)

    Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I

    2003-10-01

    An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

  3. Controversies in the treatment of digestive neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    Maria Rinzivillo; Francesco Panzuto; Gianfranco Delle Fave

    2016-01-01

    Gastroenteropancreatic neuroendocrine tumors (NETs) have an incidence of 2.39 per 100,000 inhabitants per year, and a prevalence of 35 cases per 100,000 inhabitants; the gap between these rates is due to the relatively long survival time of these tumors, which can be thus considered as chronic oncological diseases. Recently, more therapeutic options have become available, but criteria for deifning timing, priority and sequence of different therapeutic options are still debated. This review offers an overview of pancreatic and small bowel NETs, critically underlining the issues that still need to be clariifed and some controversial issues on the therapeutic approach for NET patients.

  4. Neuroendocrine Regulation of Food Intake in Polycystic Ovary Syndrome.

    Science.gov (United States)

    Daniela, Romualdi; Valentina, Immediata; Simona, De Cicco; Valeria, Tagliaferri; Antonio, Lanzone

    2017-01-01

    Several peripheral and central signals are involved in the sophisticated regulation of food intake. Women with polycystic ovary syndrome (PCOS) are prone to consume a diet higher in saturated fat and foods with high glycemic index and show impaired appetite regulation and measures of satiety. As a consequence, obesity, mostly of the central type, is prevalent in the syndrome and worsens the endocrine and metabolic profile of the affected patients. This review article briefly analyzes the current knowledge about the neuroendocrine mechanisms underlying the interplay between feeding behavior, obesity, and reproductive abnormalities in PCOS.

  5. Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2015-11-15

    Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

  6. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome

    Science.gov (United States)

    KATO, AKIHISA; HAYASHI, KAZUKI; NAITOH, ITARU; SENO, KYOJI; OKADA, YUKIKO; BAN, TESSHIN; KONDO, HIROMU; NISHI, YUJI; UMEMURA, SHUICHIRO; HORI, YASUKI; NATSUME, MAKOTO; JOH, TAKASHI

    2016-01-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin. PMID:27330779

  7. Circulating neuroendocrine tumors biomarkers. Why? When? How? Suggestions for clinical practice from guidelines and consensus

    Institute of Scientific and Technical Information of China (English)

    Paola Razzore; Giorgio Arnaldi

    2016-01-01

    Neuroendocrine neoplasms (NETs) are rare tumors that are increasing in incidence. NETs are characterized by heterogeneous biological behaviour, clinical presentation and course. A sensitive and speciifc diagnostic and prognostic circulating biomarker useful for all sites, grading and staging of neuroendocrine tumors is still an unmet need. The aim of this article was to review current neuroendocrine and oncologic scientiifc society guidelines and position statements, and propose recommendations for the most frequent clinical practice queries on circulating neuroendocrine tumors biomarkers. The authors searched for NCCN, NANETS, ESMO, ENETS, UKINETS, AME management guidelines or position statements available from PubMed up to 7th January 2016. From these results we chose guidelines or position statements published by scientiifc societies or institutions in USA, Europe and Italy with recognized expertise in neuroendocrine tumor patient management. The authors present suggestions for clinical practice based on this analysis.

  8. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  9. Specific targeting for the treatment of neuroendocrine tumors; Ciblage specifique pour le traitement des tumeurs neuro-endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Netherlands Cancer Institute 1066 CX Amsterdam, Dept. of Nuclear Medicine (Netherlands)

    2003-09-01

    For the treatment of neuroendocrine tumors three ways of specific targeting of radionuclides prevail: by {sup 131}I-meta-iodo-benzyl-guanidine (MIBG), which is taken up by an active uptake-1 mechanism and stored in neurosecretory granules of neural crest tumor cells, by radiolabeled peptides, in particular the somatostatin analogs octreotide and lanreotide, targeting the peptide receptors, and by radiolabeled antibodies, which target tumor cell surface antigens. The choice depends on the indication, the results of diagnostic imaging using tracer amounts of these agents, the availability and feasibility of radionuclide therapy and of other treatment modalities. The applications, clinical results and developments for the major indications are reviewed. {sup 131}I-MIBG therapy has a cumulative response rate of 50%, associated with little toxicity, in metastatic pheochromocytoma, paraganglioma and neuroblastoma, whereas its role is primarily palliative in patients with medullary thyroid carcinoma and carcinoid tumors. Treatment using {sup 90}Y- or {sup 177}Lu-labeled octreotide/lanreotide is mostly used in neuroendocrine gastro-entero-pancreatic (GEP) tumors and paraganglioma, attaining stabilization of disease anti-palliation in the majority of patients. As this treatment is specific for the receptor rather than for the tumor type, it may also be applicable to other, non-neuroendocrine tumors. Radioimmunotherapy is applied in medullary thyroid carcinoma, in which a phase I/II study using bi-specific anti-DTPA/anti-CEA immuno-conjugates followed by {sup 131}I-hapten has proven some degree of success, and may be used in neuroblastoma more effectively than before, once chimeric and humanized monoclonal antibodies become available for therapy. Integration of these specific and noninvasive therapies at an optimal moment into the treatment protocols of these diseases may enhance their effectiveness and acceptance. (author)

  10. Splenosis Mimicking Relapse of a Neuroendocrine Tumor at Gallium-68-DOTATOC PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Treglia, Giorgio; Luca, Giovanella [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Barbara, Muoio; Carmelo, Caldarella [Catholic Univ., Rome (Italy)

    2014-06-15

    A 48-year-old female patient underwent splenopancreasectomy for a 4-cm pancreatic neuroendocrine tumor (pNET), grade G2, located in the pancreatic tail. One year after surgery, the patient presented an increased serum level of the tumor marker chromogranin A (value: 160 U/l). Therefore, she underwent somatostatin receptor PET/CT using gallium-68-DOTATOC for restaging. This imaging method showed a focal area of increased radiopharmaceutical uptake corresponding to a 2.5-cm nodule located in the left superior abdomen near a clip from the previous surgery, suggesting a possible relapse of pNET. Based on this PET/CT finding, the patient underwent ultrasonography-guided core biopsy of this nodule. Histology did not reveal findings suggestive of pNET but identified spleen tissue most likely caused by splenosis accidentally seeded at the previous operation. It is likely that the increased serum level of the tumor marker chromogranin A was due to the chronic proton-pump inhibitors use. Somatostatin receptor PET/CT is an accurate imaging method for staging and restaging pNET, presenting high sensitivity and specificity in this setting. Nevertheless, possible sources of false-negative and -positive findings with this method should be taken into account. Inflammatory lesions represent the most frequent causes of false-positive findings for pNET at somatostatin receptor imaging because inflammatory cellsmay overexpress somatostatin receptors on their cell surface. In our case, we showed that splenosis may represent a possible cause of false-positive findings for pNET relapse due to the physiological uptake of somatostatin analogs by the spleen tissue.

  11. Whole-exome characterization of pancreatic neuroendocrine tumor cell lines BON-1 and QGP-1.

    Science.gov (United States)

    Vandamme, Timon; Peeters, Marc; Dogan, Fadime; Pauwels, Patrick; Van Assche, Elvire; Beyens, Matthias; Mortier, Geert; Vandeweyer, Geert; de Herder, Wouter; Van Camp, Guy; Hofland, Leo J; Op de Beeck, Ken

    2015-04-01

    The human BON-1 and QGP-1 cell lines are two frequently used models in pancreatic neuroendocrine tumor (PNET) research. Data on the whole-exome genetic constitution of these cell lines is largely lacking. This study presents, to our knowledge, the first whole-exome profile of the BON-1 and QGP-1 cell lines. Cell line identity was confirmed by short tandem repeat profiling. Using GTG-banding and a CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations were determined in BON-1 and QGP-1. The exomes of both cell lines were sequenced on Ilumina's HiSeq next-generation sequencing (NGS) platform. Single-nucleotide variants (SNVs) and insertions and deletions (indels) were detected using the Genome Analysis ToolKit. SNVs were validated by Sanger sequencing. Ploidy of BON-1 and QGP-1 was 3 and 4 respectively, with long stretches of loss of heterozygosity across multiple chromosomes, which is associated with aggressive tumor behavior. In BON-1, 57 frameshift indels and 1725 possible protein-altering SNVs were identified in the NGS data. In the QGP-1 cell line, 56 frameshift indels and 1095 SNVs were identified. ATRX, a PNET-associated gene, was mutated in both cell lines, while mutation of TSC2 was detected in BON-1. A mutation in NRAS was detected in BON-1, while KRAS was mutated in QGP-1, implicating aberrations in the RAS pathway in both cell lines. Homozygous mutations in TP53 with possible loss of function were identified in both cell lines. Various MUC genes, implicated in cell signaling, lubrication and chemical barriers, which are frequently expressed in PNET tissue samples, showed homozygous protein-altering SNVs in the BON-1 and QGP-1 cell lines.

  12. 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.

  13. ENETS TNM Staging Predicts Prognosis in Small Bowel Neuroendocrine Tumours

    Science.gov (United States)

    Srirajaskanthan, Rajaventhan; Ahmed, A.; Prachialias, A.; Srinivasan, P.; Heaton, N.; Jervis, N.; Quaglia, A.; Vivian, G.; Ramage, J. K.

    2013-01-01

    Introduction. Small bowel neuroendocrine tumours (NETs) are the most common type of gastrointestinal neuroendocrine tumours. The incidence and prevalence of these tumours are on the rise. The aims of this study were to determine prognostic clinicopathological features and whether the ENETS TNM staging system predicts prognosis and also. Method. Clinical data was collected retrospectively from 138 patients with histologically proven small bowel NETs managed at King's College Hospital. Histology was reviewed and small bowels tumours, were staged according to the ENETS TNM staging system. Results. Median age was 65 years (range 29–87). The 5-year survival was 79.5% and the 10-year survival was 48.5%. Resection of the primary tumour was associated with improved survival (120 versus 56 months, P TNM staging significantly separated survival of stage 2 and stage 3 from stage 4 NETs. Conclusion. Small bowel primary tumour resection and not having carcinoid heart disease are prognostic factors. The ENETS TNM staging and grading system appears to be of prognostic relevance to small bowel NETs. PMID:23533809

  14. Calcium dynamics in the secretory granules of neuroendocrine cells.

    Science.gov (United States)

    Alvarez, Javier

    2012-01-01

    Cellular Ca(2+)signaling results from a complex interplay among a variety of Ca(2+) fluxes going across the plasma membrane and across the membranes of several organelles, together with the buffering effect of large numbers of Ca(2+)-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic reticulum, mitochondria and even nucleus have all been involved in cellular Ca(2+) signaling, and the mechanisms for Ca(2+) uptake and release from these organelles are well known. In neuroendocrine cells, the secretory granules also constitute a very important Ca(2+)-storing organelle, and the possible role of the stored Ca(2+) as a trigger for secretion has attracted considerable attention. However, this possibility is frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the main questions related with granular Ca(2+) dynamics, e.g., the free granular [Ca(2+)], the physical state of the stored Ca(2+) or the mechanisms for Ca(2+) accumulation and release from the granules. This review will give a critical overview of the present state of knowledge and the main conflicting points on secretory granule Ca(2+) homeostasis in neuroendocrine cells.

  15. Pancreatic neuroendocrine tumors: biology, diagnosis,and treatment

    Institute of Scientific and Technical Information of China (English)

    Cynthia Ro; Wanxing Chai; Victoria E.Yu; Run Yu

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs),a group of endocrine tumors arising in the pancreas,are among the most common neuroendocrine tumors.The genetic causes of familial and sporadic PNETs are somewhat understood,but their molecular pathogenesis remains unknown.Most PNETs are indolent but have malignant potential.The biological behavior of an individual PNET is unpredictable; higher tumor grade,lymph node and liver metastasis,and larger tumor size generally indicate a less favorable prognosis.Endocrine testing,imaging,and histological evidence are necessary to accurately diagnose PNETs.A 4-pronged aggressive treatment approach consisting of surgery,Iocoregional therapy,systemic therapy,and complication control has become popular in academic centers around the world.The optimal application of the multiple systemic therapeutic modalities is under development; efficacy,safety,availability,and cost should be considered when treating a specific patient.The clinical presentation,diagnosis,and treatment of specific types of PNETs and familial PNET syndromes,including the novel Mahvash disease,are summarized.

  16. Morphological and functional investigations of neuroendocrine tumors of the pancreas.

    Science.gov (United States)

    Pereira, Philippe L; Wiskirchen, Jakub

    2003-09-01

    Neuroendocrine tumors of the pancreas are rare neoplasms arising predominantly from the pancreatic islets of Langerhans and are thus known as islet cell tumors. More than the half of all neuroendocrine tumors are called functioning islet cell tumors because they secrete one or more biologically active peptides that may produce clinical symptoms. Clinical diagnosis of non-functioning, i.e., biologically inactive, tumors is often delayed and patients tend to present with advanced tumors (size greater than 5 cm) that are easily localized by using conventional imaging modalities. On the other hand, symptoms of functioning islet cell tumors usually appear early in the clinical course, rendering the preoperative localization of these small hormone-producing tumors (size less than 2 cm) difficult with non-invasive methods. Since functioning islet cell tumors can often be cured by surgical resection, invasive procedures are warranted when necessary for localization diagnosis. Failure to search for, detect, and resect these small tumors will invariably result in persistent symptoms. Regarding the unsatisfactory results of morphological imaging methods, functional studies, especially arterial stimulation with hepatic venous samplings, may provide a preoperative regionalization of the pancreatic adenoma, regardless of its size.

  17. Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects.

    Science.gov (United States)

    Seibyl, J P; Krystal, J H; Price, L H; Woods, S W; D'Amico, C; Heninger, G R; Charney, D S

    1991-09-01

    Ten healthy male subjects were administered i.v. meta-chlorophenylpiperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.

  18. Are neuroendocrine tumours a feature of tuberous sclerosis? A systematic review.

    Science.gov (United States)

    Dworakowska, Dorota; Grossman, Ashley B

    2009-03-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterised by the development of multiple hamartomas in numerous organs. It is caused by mutations of two tumour suppressor genes, TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3, which encode for hamartin and tuberin respectively. The interaction between these two proteins, the tuberin-hamartin complex, has been shown to be critical to multiple intracellular signalling pathways, especially those controlling cell growth and proliferation. TSC may affect skin, central nervous system, kidneys, heart, eyes, blood vessels, lung, bone and gastrointestinal tract. Small series and case reports have documented that in tuberous sclerosis patients many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid and other neuroendocrine tissue. There have been scattered reports of the involvement of such tissue in the pathological process of TSC, but no systematic review as to whether this is a true association. We have therefore systematically assessed all available published literature in this area. We conclude that there may be an association with pituitary and parathyroid tumours, and two recent descriptions of Cushing's disease are especially intriguing. However, the evidence seems more firm in the case of islet cell tumours, particularly insulinomas. As these latter may cause changes in mental state that may be confused with the cerebral manifestations of TSC per se, it is particularly important for physicians working with these patients to be aware of the putative and indeed likely association.

  19. [Analysis of interdependence of temperament, neuroendocrine control and psychophysiological status during dry immersion].

    Science.gov (United States)

    Nichiporuk, I A

    2008-01-01

    Interdependence of temperament, hormonal and psychophysiological status was investigated in 8 young volunteers for 7-d dry immersion (DI). Blood levels of insulin, sex, steroid, thyroid hormones and psychomotor parameters were determined on DI days 3 and 7, and on day 7 of recovery. Before DI, the volunteers filled in the Kettelle personality questionnaire. During DI, anxious subjects spent less time to compare visual patterns demonstrating high and stable speed of reactions but made a bit more errors. Extraverts showed high speed of reactions and stability of psychomotor parameters and did not increase the number of errors. Easy-tempered and introvert subjects preserved inherently high insulin concentrations in DI. Support deprivation was attended by drop of the levels of triiodothyronine and cortisol and rise of prolactin and thyroxin. Results of multiple correlation analysis led to the conclusion that DI accentuates the role of original extra-introversion and dampens origin anxiety. Successfulness can be attained by adequate alteration of the levels of steroid and thyroid hormones with effectively balanced vagoinsulin-sympathoadrenal neuroendocrine control and monoaminergic CNV activity.

  20. Cognitive reappraisal increases neuroendocrine reactivity to acute social stress and physical pain.

    Science.gov (United States)

    Denson, Thomas F; Creswell, J David; Terides, Matthew D; Blundell, Kate

    2014-11-01

    Cognitive reappraisal can foster emotion regulation, yet less is known about whether cognitive reappraisal alters neuroendocrine stress reactivity. Some initial evidence suggests that although long-term training in cognitive behavioral therapy techniques (which include reappraisal as a primary training component) can reduce cortisol reactivity to stress, some studies also suggest that reappraisal is associated with heightened cortisol stress reactivity. To address this mixed evidence, the present report describes two experimental studies that randomly assigned young adult volunteers to use cognitive reappraisal while undergoing laboratory stressors. Relative to the control condition, participants in the reappraisal conditions showed greater peak cortisol reactivity in response to a socially evaluative speech task (Experiment 1, N=90) and to a physical pain cold pressor task (Experiment 2, N=94). Participants in the cognitive reappraisal group also reported enhanced anticipatory psychological appraisals of self-efficacy and control in Experiment 2 and greater post-stressor self-efficacy. There were no effects of the reappraisal manipulation on positive and negative subjective affect, pain, or heart rate in either experiment. These findings suggest that although cognitive reappraisal fosters psychological perceptions of self-efficacy and control under stress, this effortful emotion regulation strategy in the short-term may increase cortisol reactivity. Discussion focuses on promising psychological mechanisms for these cognitive reappraisal effects. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. LEPTIN AND OBESITY – NEUROENDOCRINE , METABOLIC AND ATHEROGENIC EFFECTS OF LEPTIN

    Directory of Open Access Journals (Sweden)

    Mišo Šabovič

    2003-01-01

    Full Text Available Background. Leptin is an adipocyte-derived hormone that was recently discovered. Leptin and leptin resistance play an important role in the pathogenesis of obesity. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate food intake and energy expenditure. As commonly found, obese persons have leptin resistance and consequently attenuated effects of leptin. Mechanism underlying leptin resistance has not been explained yet: it might be the result of a receptor or post receptor defect, impaired transport of leptin through cerebrovascular barrier or inactivation of leptin by binding proteins. Phase I and II clinical trials proved that recombinant leptin administration to humans is safe. First results of the current phase III clinical trials demonstrated that leptin is moderately effective in the treatment of obesity.Conclusions. Beside anti-obesity effect, leptin can have important metabolic and neuroendocrine effects. It is involved in glucose metabolism and insulin secretion, pathogenesis of polymetabolic syndrome, diabetes and arterial hypertension. In addition it affects some processes of atherothrombosis. It interacts with and significantly influences hypothalamic-pituitaryadrenal, thyroid, sexual glands and growth hormone axes. Explaining the mechanism of leptin resistance could be important for understanding the pathogenesis of obesity and associated pathologic states as polymetabolic syndrom, diabetes, arterial hipertension and atherothrombosis.

  2. Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2013-10-01

    According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

  3. Disruption of insulin signalling affects the neuroendocrine stress reaction in Drosophila females.

    Science.gov (United States)

    Rauschenbach, Inga Y; Karpova, Evgenia K; Adonyeva, Natalya V; Andreenkova, Olga V; Faddeeva, Natalya V; Burdina, Elena V; Alekseev, Alexander A; Menshanov, Petr N; Gruntenko, Nataly E

    2014-10-15

    Juvenile hormone (JH) and dopamine are involved in the stress response in insects. The insulin/insulin-like growth factor signalling pathway has also recently been found to be involved in the regulation of various processes, including stress tolerance. However, the relationships between the JH, dopamine and insulin signalling pathways remain unclear. Here, we study the role of insulin signalling in the regulation of JH and dopamine metabolism under normal and heat stress conditions in Drosophila melanogaster females. We show that suppression of the insulin-like receptor (InR) in the corpus allatum, a specialised endocrine gland that synthesises JH, causes an increase in dopamine level and JH-hydrolysing activity and alters the activities of enzymes that produce as well as those that degrade dopamine [alkaline phosphatase (ALP), tyrosine hydroxylase (TH) and dopamine-dependent arylalkylamine N-acetyltransferase (DAT)]. We also found that InR suppression in the corpus allatum modulates dopamine, ALP, TH and JH-hydrolysing activity in response to heat stress and that it decreases the fecundity of the flies. JH application restores dopamine metabolism and fecundity in females with decreased InR expression in the corpus allatum. Our data provide evidence that the insulin/insulin-like growth factor signalling pathway regulates dopamine metabolism in females of D. melanogaster via the system of JH metabolism and that it affects the development of the neuroendocrine stress reaction and interacts with JH in the control of reproduction in this species.

  4. 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.

  5. Well differentiated neuroendocrine tumor of the kidney: Report of a rare case with review of literature

    Directory of Open Access Journals (Sweden)

    Kavita Mardi

    2017-01-01

    Full Text Available Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Renal carcinoids are typically slow-growing tumors and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. We herein report a rare cases of well-differentiated NET (carcinoid in a 39-year-old male along with the immunohistochemical features. The rarity of these tumors poses a diagnostic and therapeutic challenge.

  6. Maternal separation modifies behavioural and neuroendocrine responses to stress in CCR7 deficient mice.

    Science.gov (United States)

    Harrison, Emma L; Jaehne, Emily J; Jawahar, M Catharine; Corrigan, Frances; Baune, Bernhard T

    2014-04-15

    Alterations in immune function of various humoral and cellular factors, including chemokines, secondary to early stress may play a role in the enhanced vulnerability to psychiatric conditions in those with a history of childhood adversity. C57BL/6 (WT) mice and mice deficient for the chemokine receptor type 7 (CCR7(-/-)) were used to determine the effects of maternal separation on a range of behaviours and the biological stress response. Unpredictable maternal separation (MS) was conducted for 3h daily from postnatal day 1 to 14, with subsequent behavioural testing at 10 weeks of age. Corticosterone was quantified in 11-week-old mice. Maternally separated (MS) CCR7(-/-), but not WT mice, displayed reduced interest in social novelty compared to CCR7(-/-) naïve mice. Separated CCR7(-/-) mice also exhibited significantly lower serum corticosterone concentrations compared to non-separated mice. CCR7(-/-) mice spent less time in the centre during an open field test and more time in the closed arm of the elevated zero maze compared to their wild-type (WT) controls suggesting they were more anxious, however, no difference was observed between MS and control mice in either strain or test. Together these findings suggest that CCR7 is involved in mediating social behaviour and stress response following maternal separation, whereas other behaviours such as anxiety appear to be modified by CCR7 independent of maternal separation. The observed altered cell-mediated immune function possibly underlying the behavioural and neuroendocrine differences in CCR7(-/-) mice following maternal separation requires further investigation.

  7. Impact of scorpion venom as an acute stressor on the neuroendocrine-immunological network.

    Science.gov (United States)

    Santhosh, K N; Pavana, D; Thippeswamy, N B

    2016-11-01

    Although immunomodulatory property and many other pharmaceutical applications of scorpion venom have been addressed before, no studies were reported about its application as a neuroimmunomodulator at therapeutic dose. In this study, we conceptualized the property of scorpion venom, capable of inducing the acute pain and neurotoxicity can cause acute stress resulting in the modulation of immune cells through HPA axis. The whole venom from Hottentotta rugiscutis, a widely seen scorpion in the region of eastern Karnataka, was extracted and injected a single dose of 1 mg/kg b.w. to Swiss albino mice and then erythrocytes and leukogram were measured. Whole brain AChE activity, corticosterone, cytokines and NO levels in plasma were also evaluated at various time points. Hrv didn't show any histopathological changes in the lymphoid organs and at the site of injection. However, lymphocytes and neutrophils did get altered at 2 h post-injection. Plasma corticosterone, cytokine levels such as IL-1β, IL-6, TNF-α and IL-10 and the AChE activity were significantly increased in a time-dependent manner. Based on these results, it may be predicted, Hrv's ability to cause acute stress resulted in the activation of HPA axis, which stimulates the release of glucocorticoid hormones which in turn elicits the immunomodulation of leukocytes by altering the levels of pro and anti-inflammatory cytokines. Thus, we can conclude, the impact of acute stress induced by Hrv can intercommunicate the signals between neuroendocrine-immune systems.

  8. 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.

  9. [Neuroendocrine dysfunction and brain damage. A consensus statement].

    Science.gov (United States)

    Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

    2009-01-01

    This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

  10. Pulmonary neuroendocrine tumor in a female wolf (Canis lupus lupus)

    Science.gov (United States)

    SHIRAKI, Ayako; YOSHIDA, Toshinori; KAWASHIMA, Masahi; MURAYAMA, Hirotada; NAGAHARA, Rei; ITO, Nanao; SHIBUTANI, Makoto

    2017-01-01

    A 17-year-old female wolf (Canis lupus lupus) had a right lung mass that was adhered to the thoracic cavity. Histopathological examination revealed that the mass consisted of sheets, cord or ribbon-like structures of monotonous, small, cuboidal cells with round, oval or short-spindle nuclei and scant clear cytoplasm, demarcated by a fine fibrovascular stroma. Focal necrosis, congestion and thrombi were observed. Immunohistochemically, the tumor cells diffusely expressed cytokeratin AE1/AE3, and some expressed chromogranin A, neural cell adhesion molecule (CD56) and thyroid transcription factor-1. The number of proliferating cell nuclear antigen-positive tumor cells was low. A diagnosis of pulmonary neuroendocrine tumor was based on the resemblance to carcinoids. PMID:28190820

  11. Mixed acinar-neuroendocrine carcinoma of the pancreas

    DEFF Research Database (Denmark)

    Jakobsen, Mark; Klöppel, Günter; Detlefsen, Sönke

    2016-01-01

    A 62-year-old woman presented with abdominal discomfort. Imaging studies showed a tumor in the pancreatic tail. At contrast-enhanced CT and macroscopy, the tumor showed cystic, solid and hemorrhagic areas. Histologically, the tumor was well-circumscribed and entirely encapsulated. Some of the tum...... controversial. Due to the small number of cases it is at present not possible to define an evidence-based optimal treatment strategy for these patients....... 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...

  12. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    Institute of Scientific and Technical Information of China (English)

    Tomohide; Hori; Kyoichi; Takaori; Shinji; Uemoto

    2014-01-01

    Pancreatic neuroendocrine tumor(P-NET) is rare and slow-growing. Current classifications predict its progno-sis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of pa-tients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indi-cated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally con-ceived as an ideal therapy for unresectable liver metas-tases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases.

  13. Neuroendocrine mechanism of seasonal reproduction in birds and mammals.

    Science.gov (United States)

    Yoshimura, Takashi

    2010-08-01

    In temperate zones, animals use changes in day length as a calendar to time their breeding season. However, the photoreceptive and neuroendocrine mechanisms of seasonal reproduction are considered to differ markedly between birds and mammals. This can be understood from the fact that the eye is the only photoreceptive organ, and melatonin mediates the photoperiodic information in mammals, whereas in birds, photoperiodic information is directly received by the deep brain photoreceptors and melatonin is not involved in seasonal reproduction. Recent molecular and functional genomics analysis uncovered the gene cascade regulating seasonal reproduction in birds and mammals. Long day-induced thyroid stimulating hormone in the pars tuberalis of the pituitary gland regulates thyroid hormone catabolism within the mediobasal hypothalamus. Further, this local thyroid hormone catabolism appears to regulate seasonal gonadotropin-releasing hormone secretion. These findings suggest that although the light input pathway is different between birds and mammals (i.e. light or melatonin), the core mechanisms are conserved in these vertebrates.

  14. An unusual presentation of "silent" disseminated pancreatic neuroendocrine tumor

    Institute of Scientific and Technical Information of China (English)

    Dragomir Marisavljevic; Natasa Petrovic; Nikola Milinic; Vesna Cemerikic; Miodrag Krstic; Olivera Markovic; Dragoljub Bilanovic

    2004-01-01

    To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome.We reported a 58-year old male patient who presented with long standing,prominent cervical lymphadenopathy and occasional watery diarrhea.Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor,which was histological type A of carcinoid (EMA+,cytokeratin+,CEA-,NSE+,chromogranin A+,synaptophysin+,insulin-).Bone marrow biopsy showed identical findings.Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance.However,serotonin levels in blood and urine samples were normal.It is difficulty to establish the precise diagnosis of a "functionally inactive" pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.

  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. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  17. Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia.

    Science.gov (United States)

    Maasberg, Sebastian; Knappe-Drzikova, Barbora; Vonderbeck, Dorothée; Jann, Henning; Weylandt, Karsten H; Grieser, Christian; Pascher, Andreas; Schefold, Jörg C; Pavel, Marianne; Wiedenmann, Bertram; Sturm, Andreas; Pape, Ulrich-Frank

    2017-01-01

    Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. When applying malnutrition screening scores, 21-25% of the NEN patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, by determination of serum surrogate parameters such as albumin as well as by bioelectrical impedance analysis (BIA), particularly phase angle α. The length of hospital stay was significantly longer in malnourished NEN patients, while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk of malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3 NEC). Malnutrition is therefore an underrecognized problem in NEN patients which should systematically be diagnosed by widely available standard methods such as Nutritional Risk Screening (NRS), serum albumin assessment and BIA, and treated to improve both short- and long-term outcomes. © 2015 S. Karger AG, Basel.

  18. Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor.

    Science.gov (United States)

    Almeida, O F; Hassan, A H; Holsboer, F

    1993-01-01

    Most studies of the neuroendocrine effects of corticotropin-releasing factor (CRF) have focused on its role in the regulation of the pituitary-adrenal axis; activation of this axis follows release of the peptide from CRF-containing terminals in the median eminence. However, a sizeable proportion of CRF fibres terminate within the hypothalamus itself, where synaptic contacts with other hypothalamic neuropeptidergic neurons (e.g. gonadotropin-releasing hormone-containing and opioidergic neurons) have been identified. Here, we summarize physiological and pharmacological data which provide insights into the nature and significance of these intrahypothalamic connections. It is now clear that CRF is a potent secretagogue of the three major endogenous opioid peptides (beta-endorphin, Met-enkephalin and dynorphin) and that it stimulates opioidergic neurons tonically. In the case of beta-endorphin, another hypothalamic peptide, arginine vasopressin, appears to be an essential mediator of CRF's effect, suggesting the occurrence of CRF synapses on, or in the vicinity of, vasopressin neurons; morphological support for this assumption is still wanting. Evidence for direct and indirect inhibitory effects of CRF on sexual behaviour and secretion of reproductive hormones is also presented; the indirect pathways include opioidergic neurons. An important conclusion from all these studies is that, in addition to its better known functions in producing adaptive responses during stressful situations, CRF might also contribute to the coordinated functioning of various components of the neuroendocrine system under basal conditions. Although feedback regulation of hypothalamic neuronal activity by peripheral steroids is a well-established tenet of endocrinology, data on modulation of the intrahypothalamic actions of CRF by adrenal and sex steroids are just emerging. Some of these newer findings may be useful in framing questions related to the mechanisms underlying disease states (such as

  19. Risk factors for aggressive nonfunctional pancreatic neuroendocrine tumors and the role of endoscopic ultrasound guided fine-needle aspiration

    Science.gov (United States)

    Ende, Alexander R.; Sedarat, Alireza; Shah, Pari; Jhala, Nirag; Fraker, Douglas L.; Drebin, Jeffrey A.; Metz, David C.; Kochman, Michael L.

    2016-01-01

    Background: Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are increasingly being diagnosed but management, especially of small tumors, remains a clinical dilemma. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is now routinely used for diagnosis of pancreatic neuroendocrine tumors (pNETs) but has not been well studied as a tool for identifying aggressive disease. Materials and Methods: A systematic search of the cytology database identified all patients at our center who underwent EUS-FNA from 1999 through 2011 and were diagnosed with NF-pNET. Results: A total of 50 patients were identified. Though patients with metastatic disease had a mean tumor size of 40 mm compared to 25 mm in patients without metastatic disease (P = 0.04), we also identified several patients with tumors 20 mm (P = 0.13). Using receiver operating characteristic (ROC) analysis, we found that using a cutoff point of 20 mm only led to a sensitivity of 85% in screening for metastases, while lowering the cutoff point to 18 mm allowed for a sensitivity of 95%. Conclusion: Currently, guidelines suggest that only patients with tumors greater than 20 mm undergo surgical resection, as tumors less than this size are thought to have low risk of metastases. Our analysis suggests that these recommendations could lead to undertreating patients with small tumors. Tumor size alone may be inadequate as a marker for aggressive NF-pNETs. Given this, other risk factors for aggressive pNETs should be studied to help identify the patients most likely to benefit from surgery. PMID:26879167

  20. Actions of Bisphenol A and Bisphenol S on the Reproductive Neuroendocrine System During Early Development in Zebrafish.

    Science.gov (United States)

    Qiu, Wenhui; Zhao, Yali; Yang, Ming; Farajzadeh, Matthew; Pan, Chenyuan; Wayne, Nancy L

    2016-02-01

    Bisphenol A (BPA) is a well-known environmental, endocrine-disrupting chemical, and bisphenol S (BPS) has been considered a safer alternative for BPA-free products. The present study aims to evaluate the impact of BPA and BPS on the reproductive neuroendocrine system during zebrafish embryonic and larval development and to explore potential mechanisms of action associated with estrogen receptor (ER), thyroid hormone receptor (THR), and enzyme aromatase (AROM) pathways. Environmentally relevant, low levels of BPA exposure during development led to advanced hatching time, increased numbers of GnRH3 neurons in both terminal nerve and hypothalamus, increased expression of reproduction-related genes (kiss1, kiss1r, gnrh3, lhβ, fshβ, and erα), and a marker for synaptic transmission (sv2). Low levels of BPS exposure led to similar effects: increased numbers of hypothalamic GnRH3 neurons and increased expression of kiss1, gnrh3, and erα. Antagonists of ER, THRs, and AROM blocked many of the effects of BPA and BPS on reproduction-related gene expression, providing evidence that those three pathways mediate the actions of BPA and BPS on the reproductive neuroendocrine system. This study demonstrates that alternatives to BPA used in the manufacture of BPA-free products are not necessarily safer. Furthermore, this is the first study to describe the impact of low-level BPA and BPS exposure on the Kiss/Kiss receptor system during development. It is also the first report of multiple cellular pathways (ERα, THRs, and AROM) mediating the effects of BPA and BPS during embryonic development in any species.

  1. Population Pharmacokinetic Analysis of Lanreotide Autogel/Depot in the Treatment of Neuroendocrine Tumors: Pooled Analysis of Four Clinical Trials.

    Science.gov (United States)

    Buil-Bruna, Núria; Garrido, María Jesús; Dehez, Marion; Manon, Amandine; Nguyen, Thi Xuan Quyen; Gomez-Panzani, Edda L; Trocóniz, Iñaki F

    2016-04-01

    Lanreotide Autogel (lanreotide Depot in the USA) has demonstrated anti-tumor activity and control of the symptoms associated with hormone hypersecretion in patients with neuroendocrine tumors. The objectives of this study were to describe the pharmacokinetics of lanreotide Autogel administered 4-weekly by deep subcutaneous injections of 60, 90, or 120 mg in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to quantify the magnitude of inter-patient variability (IPV), and to identify those patient characteristics that impact on pharmacokinetics. Analyses were based on pooled data from clinical trials. A total of 1541 serum concentrations from 290 patients were analyzed simultaneously by the population approach using NONMEM version 7.2. Covariates evaluated included demographics, renal and hepatic function markers, and disease-related parameters. Serum profiles were described by a one-compartment disposition model in which the absorption process was characterized by two parallel pathways following first- and zero-order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day, representing a substantial difference in clearance in this population of patients with respect to healthy volunteers that could not be explained by any of the covariates tested. Body weight was the only covariate to show a statistically significant effect on the pharmacokinetic profile, but due to the overlap between the pharmacokinetic profiles of patients with lower or higher body weights the effect of body weight on clearance was not considered clinically relevant. The IPV was low for clearance (27%) and moderate to high for volume of distribution (150%) and the absorption constant (61%). Using two mechanisms of absorption, the pharmacokinetics of lanreotide Autogel were well-described in patients with GEP-NET. None of the patient characteristics tested were of clinical

  2. SPECT/CT in neuroendocrine cancers; SPECT/CT bei neuroendokrinen Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Miederer, M. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Mainz Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Castrop, C.; Scheidhauer, K. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Buck, A.K. [Universitaetsklinikum Wuerzburg (Germany). Nuklearmedizinische Klinik und Poliklinik

    2011-03-15

    The accuracy of functional SPECT imaging has been significantly improved by addition of CT. This is especially relevant for functional imaging of neuroendocrine tumors using highly specific radiopharmaceuticals. Parathyroid adenomas can be detected by {sup 99m}Tc-MIBI SPECT/CT with very high sensitivity and specificity, playing an important role especially when minimally invasive techniques are used for surgical resection. With SPECT/CT, extra-adrenal manifestations of pheochromocytomas and tumors of the adrenal cortex can be detected with high accuracy. Because of the availability of PET radiopharmaceuticals such as {sup 68}Ga-DOTATOC, the clinical relevance of {sup 111}In-Octreotide SPECT for detection of neuroendocrine cancers has been recently reduced. Because of the better availability, SPECT and SPECT/CT still represent standard tools for imaging neuroendocrine cancers. SPECT/CT represents the superior imaging modality for monitoring radiopeptide based therapies, which are now increasingly used for treatment of neuroendocrine cancers. (orig.)

  3. Middle ear adenoma with neuroendocrine differentiation: relate of two cases and literature review

    Science.gov (United States)

    Bittencourt, Aline Gomes; Tsuji, Robinson Koji; Cabral, Francisco; Pereira, Larissa Vilela; Fonseca, Anna Carolina de Oliveira; Alves, Venâncio; Bento, Ricardo Ferreira

    2013-01-01

    Summary Introduction: Adenomas with neuroendocrine differentiation are defined as neuroendocrine neoplasms, and they are rarely found in the head and neck. Objective: To describe two cases of a middle ear adenoma with neuroendocrine differentiation, with a literature review. Case Report: Patient 1 was a 41-year-old woman who presented with a 3-year history of left aural fullness associated with ipsilateral “hammer beating” tinnitus. Patient 2 was a 41-year-old male who presented with unilateral conductive hearing loss. Conclusion: Adenoma with neuroendocrine differentiation of the middle ear is a rare entity, but it should be considered in patients with tinnitus, aural fullness, and a retrotympanic mass and remembered as a diferential diagnosis of tympanic paraganglioma. PMID:25992031

  4. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    DEFF Research Database (Denmark)

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S;

    2015-01-01

    Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for...

  5. Basaloid squamous carcinoma of the supraglottic larynx with neuro-endocrine features

    Directory of Open Access Journals (Sweden)

    Rajjyoti Das

    2015-01-01

    Full Text Available Basaloid squamous carcinoma (BSC is a rare aggressive variant of squamous cell carcinoma and occurs mainly at the larynx, oropharynx and tongue of the head and neck region. Neuro-endocrine differentiation of BSC is further rare occurrence in laryngeal cancers. We report here a case of BSC of supraglottic larynx with neuro-endocrine differentiation, which was treated by radiotherapy and its response to treatment.

  6. Stress and the neuroendocrine system: the role of exercise as a stressor and modifier of stress

    OpenAIRE

    Hackney, Anthony C

    2006-01-01

    In this article, the physiological impact of one form of stress – physical exercise – on the neuroendocrine system will be discussed. The specific intent of the review is to present an overview of stress endocrinology, the conceptual models associated with this area of study, and a discourse on the dual role of exercise as both a stressor and a modifier of stress within the neuroendocrine system. These points are addressed with respect to the current research literature dealing with exercise ...

  7. Small Cell Neuroendocrine Carcinoma of the Urinary Tract Successfully Managed with Neoadjuvant Chemotherapy

    OpenAIRE

    Mustapha Ahsaini; Omar Riyach; Mohammed Fadl Tazi; Mohammed Jamal El Fassi; My Hassan Farih; Hind Elfatmi; Afaf Amarti

    2013-01-01

    Introduction. Small cell neuroendocrine carcinomas of the urinary tract is an extremely rare entity and very few cases have been reported in the literature. Small cell neuroendocrine carcinoma of the urinary tract (SCC-UT) is the association between bladder and urinary upper tract-small cell carcinoma (UUT-SCC). It characterized by an aggressive clinical course. The prognosis is poor due to local or distant metastases, and usually the muscle of the bladder is invaded. Case Presentation. We...

  8. Neuroendocrine Cell Hyperplasia of Infancy: Diagnosis With High-Resolution CT

    Science.gov (United States)

    Brody, Alan S.; Guillerman, R. Paul; Hay, Thomas C.; Wagner, Brandie D.; Young, Lisa R.; Deutsch, Gail H.; Fan, Leland L.; Deterding, Robin R.

    2013-01-01

    OBJECTIVE Neuroendocrine cell hyperplasia of infancy is a form of childhood interstitial lung disease originally reported as persistent tachypnea of infancy. Reports of small series of cases and anecdotal experience have suggested that this disorder may have a consistent CT pattern. The purpose of this study was to review the CT findings in children with neuroendocrine cell hyperplasia of infancy to determine the findings at high-resolution CT, the diagnostic accuracy of CT compared with biopsy, and interrater reliability. MATERIALS AND METHODS Images from 23 CT examinations of children with biopsy-proven neuroendocrine cell hyperplasia of infancy and six CT examinations of children with other childhood interstitial lung diseases were reviewed by two pediatric radiologists with special expertise in thoracic imaging. Identifying digital data were removed, and images were reviewed without clinical data. A CT assessment form was completed for each patient. RESULTS Ground-glass opacification was the most common finding in patients with neuroendocrine cell hyperplasia of infancy. The right middle lobe and lingula were most commonly involved. Air trapping with a mosaic pattern was the second most common finding. Interrater reliability was very good with a kappa value of 0.93. The sensitivity and specificity of CT in the diagnosis of neuroendocrine cell hyperplasia of infancy were at least 78% and 100%. CONCLUSION Neuroendocrine cell hyperplasia of infancy can have a characteristic appearance on high-resolution CT scans, the imaging findings being useful in differentiating neuroendocrine cell hyperplasia of infancy from other types of childhood interstitial lung disease. The appearance aids radiologists in suggesting a specific diagnosis but does not exclude this diagnosis; in 17–22% of cases, the readers in this study did not suggest the diagnosis of neuroendocrine cell hyperplasia of infancy when it was present. PMID:20028928

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Tumour markers in gastrointestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lamerz, R.

    1988-02-01

    For non-endocrine gastrointestinal tumours the following tumour markers are of clinical interest: For esophageal cancer CEA (sensitivity, s: 40-60%) and SCC (squamous cell carcinoma antigen, x: 20-50%); for gastric cancer CEA (s: 30-40%) as well as CA 19-9 (s: 30-40%) because of complementary results (additive s: 50-60); for hepatocellular cancer AFP (first choice, s: 70-90%; second choice CA 19-9, s: 50-70%); for cholangiocellular cancer CA 19-9 (s: 40-70%); for secondary liver cancer in general CEA; for biliary tract cancer CA 19-9 (s: 40-70%) as well as for excretory pancreatic cancer (s: 70-90%); for colorectal cancer CEA (s: 40-70%) as a first choice marker, and CA 19-9 (s: 20-60%) as a second choice marker, and for anal cancer SCC. The frequency of tumour marker determinations depends on follow-up care recommendations for different tumour diseases (e.g. 1-3 monthly during the 1st and 2nd postoperative year, following chemotherapy courses, on change of therapy, on restaging and at unclear alteration of the clinical state). Tumour markers are only valuable adjuncts to the medical care of tumour patients and therefore useless as solitary findings or on missing therapeutic consequence.

  11. Effect of Semecaprus anacardium on diabetes-induced alterations in the activities of marker enzymes and antioxidant enzymes in type 2 diabetes induced cardiac vascular damage model in rats.

    Science.gov (United States)

    Subramaniam, Suganthi; Khan, Haseena Banu Hedayathullah; Gomathy, G; Palanvelu, Shanthi; Panchanadham, Sachidanandam Tiruvaiyaru

    2014-12-01

    Semecarpus anacardium is a commonly used drug in the Siddha system of medicine for curing various metabolic disorders. The cardio protective effect of the drug in Type 2 diabetes-induced cardiovascular complications was studied in rats by feeding them with a high fat diet for 2 weeks followed by intra peritoneal injection of streptozotocin at a moderate dosage of 2*35 mg/kg/ b.wt 24 hr apart and leaving them for 8 weeks to develop cardiovascular complications. The effect of the drug was studied by analyzing levels of blood glucose, insulin, HbA1c, marker enzymes, the antioxidative enzymes and the levels of lipid peroxides in Type 2 diabetic rats. Diabetic rats were treated with SA at a dosage of 300 mg/kg/b.wt. for 8 weeks and the results were compared with diabetic rats treated with the combination therapy drugs metformin at a dosage of 100 mg/kg/b.wt and atorvastatin at a dosage of 10 mg/kg/b.wt for 8 weeks. The drug SA significantly decreased the blood glucose levels and also HbA1c levels while improving glucose tolerance at the same time. The levels of marker enzymes and lipid peroxides were significantly increased in diabetic rats when compared with control rats. On the other hand significant decreases in the levels of antioxidative enzymes were observed in diabetic rats. Upon treatment with the drug SA, all of these abnormalities were restored to near normalcy. The present study thereby establishes the protective effect of the drug against diabetes-induced cardiac damage.

  12. Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors

    Science.gov (United States)

    van Adrichem, R C S; Hofland, L J; Feelders, R A; De Martino, M C; van Koetsveld, P M; van Eijck, C H J; de Krijger, R R; Sprij-Mooij, D M; Janssen, J A M J L; de Herder, W W

    2013-01-01

    Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied. Tumoral mRNA expression of IGF-related genes (IGFs: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients. PMID:24042314

  13. 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

  14. Endoscopic resection of duodenal bulb neuroendocrine tumor larger than 10 mm in diameter

    Directory of Open Access Journals (Sweden)

    Naka Teiji

    2011-06-01

    Full Text Available Abstract Background Endoscopic treatment for duodenal bulb neuroendocrine tumor larger than 10 mm is still controversial. This report presents four cases successfully treated with endosonography (EUS-assisted endoscopic mucosal resection (EMR procedure for duodenal bulb neuroendocrine tumor larger than 10 mm in diameter. Methods The case series of four patients diagnosed with neuroendocrine tumor from 2003 to 2008 were reviewed. EUS demonstrated well-defined hypoechoic tumors confined to the submucosal hyperechoic layer and the underlying hypoechoic muscularis propria was intact in all four patients. EMR were planned and performed for the duodenal bulb neuroendocrine tumors larger than 10 mm. Results En bloc resections with tumor free lateral and basal margins were accomplished using an endoscopic diathermic snare with forward-viewing instruments without any complications. Neither residual duodenal neuroendocrine tumors nor metastatic lesions were detected during the observation period ranging 19 to 78 months Conclusion Duodenal bulb neuroendocrine, larger than 10 mm in diameter, can be treated by endoscopic procedure, after confirming that the tumor confined to the submucosal layer in EUS examination, and no lymph node involvement by abdominal CT and US.

  15. Alterations in the expression of the NF-κB family member RelB as a novel marker of cardiovascular outcomes during acute exacerbations of chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Laura Labonté

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-κB activation. RelB, an NF-κB family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown. Moreover, there is no information on its association with clinical features of COPD. The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation. METHODS: Data from 48 COPD patients were analyzed. Blood samples were collected from stable-state and exacerbating patients. After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR was performed to assess RelB, Cox-2, IL-8 and IL-1β mRNA expression and their associations with measured clinical variables. RESULTS: Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation. RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1β in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22. Cox-2, IL-8 and IL-1β were significantly associated with clinical features of patients in both stable-state and at exacerbation. There was no association with RelB expression and any clinical features in COPD subjects at stable-state. RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation. CONCLUSIONS: RelB mRNA expression is lower than that of the other inflammatory mediators. Expression of Cox-2, IL-8 and IL-1β were related to clinical features in both stable-state and at exacerbation. However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD.

  16. 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 neuroendocrine...... tumours. These guidelines essentially cover basic knowledge in the diagnosis and management of the different forms of neuroendocrine tumour. We have, however, tried to give more updated information about the epidemiology and histopathology, which is essential for the clinical management of these tumours....

  17. 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

  18. Intracerebroventricular leptin injection affects neuroendocrine reproductive axis in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yuebing Qiao; Huixian Cui

    2008-01-01

    BACKGROUND: Leptin regulates neuroendocrine function of the hypothalamus-pituitary-ovary axis in humans.OBJECTIVE: To verify effects of intracerebroventricular leptin injection on neuroendocrine function of the hypothalamus-pituitary-ovary axis in nvariectomized rats.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Basic Medical Institute, Chengde Medical College between June and October 2007.MATERIALS: Thirty healthy, female, Wistar rats were included in this study. The following compounds were used: leptin; gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) enzyme-linked immunosorbent assay kits.METHODS: Rats were randomly divided into 3 groups at 1, 2, and 4 hours after injection. Each group was subdivided into control and experimental groups (n = 5 animals per group and time point). All rats were subjected to bilateral ovariectomy and, beginning on day 7 after surgery, animals received daily subcutaneous injections of estradiol benzoate (2 μ g) for 7 consecutive days. The experimental groups were injected with 5 μ L leptin (1 g/L) into the lateral cerebral ventricle, and control groups received an equal volume of physiological saline.MAIN OUTCOME MEASURES: GnRH and LH secretion were examined 1, 2, and 4 hours after injection using GnRH and LH ELISA kits, respectively.RESULTS: In the experimental groups, GnRH secretion significantly increased (P < 0.01), followed by LH secretion (P < 0.01), compared with the control groups. GnRH secretion significantly increased l hour after leptin injection (P < 0.01). The LH increase was less pronounced, but still significant (P < 0.01); however,the most prominent LH increase occurred between 1 and 2 hours. Both GnRH and LH secretion reached peak levels at 2 hours after leptin injection. Thereafter, both GnRH and LH secretion decreased, but still maintained very high levels, compared with the control group (P < 0.01).CONCLUSION: lntracerebroventricular leptin injection

  19. Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, M.; Breeman, A.P.; Bernard, H.F.; Kooij, P.P.M.; Kwekkeboom, D.J.; Valkema, R. [Rotterdam University Hospital and Erasmus University, Rotterdam (Netherlands). Internal Medicine; Van Eijck, C.H.J.; Slooter, G.D. [Basel Surgery, Basel (Switzerland). Dept. of Nuclear Medicine; Maecke, H.R.; Krenning, E.P. [Basel Kantonspital, Basel (Switzerland). Dept. of Nuclear Medicine

    1999-12-01

    Peptide receptor scintigraphy with the radioactive somatostatin-analogue ({sup 111}In-DTPA{sup 0})octreotide (DTPA=diethylenetriaminepentaacetic acid) is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. A new application is the use of peptide receptor radionuclide therapy, administrating high doses of {sup 111}In- or {sup 90}Y-labeled octreotide-analogues. In the preclinical situation it was investigated on the radiotherapeutic effect of {sup 90}Y- and {sup 111}In-labeled (DOTA{sup 0}, Tyr{sup 3})octreotide (DOTA=tetraazacyclododecanetetraacetic acid) or ({sup 111}In-DTPA{sup 0})octreotide in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumor CA20948 in (A) the flank of (B) in the liver. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with ({sup 111}In-DTPA{sup 0})octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase 1 trial. (A) Flank model: at least two 111MBq injections of ({sup 111}In-DOTA{sup 0}, Tyr{sup 3})octreotide were needed to reach tumor response, in 40% of the animals complete tumor remission was found after a follow-up period of 10 months. One or two injections of ({sup 90}Y-DOTA{sup 0}, Tyr{sup 3})octreotide yielded transient stable disease. (B) Liver model: it was found that peptide receptor radionuclide therapy is only effective if somatostatin receptors are present on the tumors, and is therefore receptor-mediated. High radioactive doses of 370 MBq ({sup 111}In-DTPA{sup 0})octreotide or 93 MBq ({sup 90}Y-DOTA{sup 0}, Tyr{sup 3})octreotide can inhibit the growth of somatostatin receptor-positive metastases. There were no major clinical side effects after up to 2 years treatment, except that a transient decline in platelet counts and lymphocyte subsets can occur

  20. Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors.

    Science.gov (United States)

    Palazzo, Maxime; Lombard-Bohas, Catherine; Cadiot, Guillaume; Matysiak-Budnik, Tamara; Rebours, Vinciane; Vullierme, Marie-Pierre; Couvelard, Anne; Hentic, Olivia; Ruszniewski, Philippe

    2013-02-01

    An antiproliferative effect of somatostatin analogs was recently demonstrated. To identify factors associated with tumor control in a group of patients with well-differentiated malignant digestive neuroendocrine tumors treated with lanreotide. A retrospective study was conducted in 68 patients treated with lanreotide alone, with progression-free survival as the primary endpoint. The role of the following factors was searched for by univariate and multivariate analyses: age, sex, mode of discovery, site of the primary tumor, metastatic spread, Ki67 proliferation index, uptake on somatostatin receptor scintigraphy, pretreatment tumor growth, extent of liver involvement, resection of primary tumor, previous treatments, and tumor markers. Tumor progression was observed in 39/68 patients (57.4%). Median progression-free survival was 29 months. On multivariate analysis, a Ki67 proliferation index of up to 5% [hazard ratio (HR)=0.262, P=0.009], pretreatment stability (HR=0.241, P=0.008), and hepatic tumor load of up to 25% (HR=0.237, P=0.004) were significantly associated with disease stability under lanreotide therapy. In patients with well-differentiated malignant digestive neuroendocrine tumors, Ki67 proliferation index of up to 5%, stable disease before treatment, and low-to-moderate hepatic tumor involvement (≤ 25%) are associated with tumor control during lanreotide treatment. These data if confirmed in prospective trials will help in rationalizing the use of somatostatin analogs with antiproliferative intent.

  1. Practice guidelines for tumor marker use in the clinic.

    Science.gov (United States)

    Sturgeon, Catharine

    2002-08-01

    Increasing interest in implementing the practice of evidence-based medicine in oncology has encouraged the development of clinical guidelines, many of which include recommendations about the appropriate use of serum tumor markers. Recent national and international guidelines relating to the use of tumor markers in germ cell, colorectal, breast, ovarian, prostate, lung, neuroendocrine, and thyroid cancers were identified from the scientific literature and other sources and tabulated. Guideline recommendations developed by national and international groups and relating to the use of tumor markers for specific cancers are reviewed and compared, considering the recommendations made for their use in screening, diagnosis, prognosis, and monitoring of therapy. Potential advantages and disadvantages of clinical guidelines, how best to implement them, and means of auditing their effectiveness are also considered. Excellent clinical guidelines, including recommendations for the most appropriate use of tumor markers, are already available for many cancers. Many questions relating to optimal use of these important tests remain to be answered, but current guidelines already contain much valuable information and advice. Further dissemination and implementation of the guidelines should encourage better use of tumor markers in clinical practice. Careful audit studies are also required to establish the impact of these guidelines on the practice of evidence-based medicine.

  2. Impact of Helicobacter pylori infection on ghrelin and various neuroendocrine hormones in plasma

    Institute of Scientific and Technical Information of China (English)

    Hajime Isomoto; Hiroaki Ueno; Yoshito Nishi; Chun-Yang Wen; Masamitsu Nakazato; Shigeru Kohno

    2005-01-01

    AIM: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, influences appetite, energy balance, gastric motility and acid secretion. The stomach is the main source of circulating ghrelin. There are inconsistent reports on the influence of Helicobacter pylori (H pylori) infection on circulating ghrelin levels. We sought to elucidate the relationship between ghrelin and various peptides in plasma, with special reference to H pylori.METHODS: Plasma ghrelin levels were measured by radioimmunoassay in 89 subjects who were referred for upper gastrointestinal endoscopy, consisting of 42 H pylori infected and 47 uninfected ones. Plasma gastrin,somatostatin, leptin, insulin-like growth hormone 1 (IGF-1)and chromogranin A concentrations were also measured.Twelve patients were treated with anti- H pylori regimen.RESULTS: Ghrelin circulating levels were greatly decreased in H pylori-positive than negative individuals (194.2±90.2fmol/mL and 250.4±84.1 respectively, P<0.05), but did not significantly alter following the cure of infection (176.5±79.5 vs 191.3±120.4). There was a significant negative correlation between circulating ghrelin and leptin levels, as well as body mass index, for the whole and uninfected population, but not in H pylori-infected patients. Plasma ghrelin concentrations correlated positively with IGF-1 in H pylori-negative group and negatively with chromogranin A in the infected group.There were no significant correlations among circulating levels of ghrelin, gastrin and somatostatin irrespective of H pylori status.CONCLUSION: H pylori infection influences plasma ghrelin dynamics and its interaction with diverse bioactive peptides involved in energy balance, growth and neuroendocrine function.

  3. Neuroendocrine mechanisms of change in food intake during pregnancy: a potential role for brain oxytocin.

    Science.gov (United States)

    Douglas, Alison J; Johnstone, Louise E; Leng, Gareth

    2007-07-24

    During pregnancy body weight, and particularly adiposity, increase, due to hyperphagia rather than decreased energy metabolism. These physiological adaptations provide the growing fetus(es) with nutrition and prepare the mother for the metabolically-demanding lactation period following birth. Mechanisms underlying the hyperphagia are still poorly understood. Although the peripheral signals that drive appetite and satiety centers of the brain are increased in pregnancy, the brain may become insensitive to their effects. For example, leptin secretion increases but hypothalamic resistance to leptin actions develops. However, several adaptations in hypothalamic neuroendocrine systems may converge to increase ingestive behavior. Oxytocin is one of the anorectic hypothalamic neuropeptides. Oxytocin neurons, both centrally-projecting parvocellular oxytocin neurons and central dendritic release of oxytocin from magnocellular neurons, may play a key role in regulating energy intake. During feeding in non-pregnant rats, magnocellular oxytocin neurons, especially those in the supraoptic nucleus, become strongly activated indicating their imminent role in meal termination. However, in mid-pregnancy the excitability of these neurons is reduced, central dendritic oxytocin release is inhibited and patterns of oxytocin receptor binding in the brain alter. Our recent data suggest that lack of central oxytocin action may partly contribute to maternal hyperphagia. However, although opioid inhibition is a major factor in oxytocin neuron restraint during pregnancy and opioids enhance food intake, an increase in opioid orexigenic actions were not observed. While changes in several central input pathways to oxytocin neurons are likely to be involved, the high level of progesterone secretion during pregnancy is probably the ultimate trigger for the adaptations.

  4. The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

    Science.gov (United States)

    Bianchi, A; De Marinis, L; Fusco, A; Lugli, F; Tartaglione, L; Milardi, D; Mormando, M; Lassandro, A P; Paragliola, R; Rota, C A; Della Casa, S; Corsello, S M; Brizi, M G; Pontecorvi, A

    2011-10-01

    The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

  5. Neuroendocrine carcinoma of the ovotestis: A case report and review of literatures

    Science.gov (United States)

    Ashrafganjoei, Tahereh; Sourati, Ainaz; Mohamadianamiri, Mahdiss

    2016-01-01

    Background: Neuroendocine carcinoma of the gynecologic tract is rare and poses a significant clinical challenge because of tumor heterogeneity and lack of standardized guidelines for treatment. Ovotestis refers to the histology of a gonad that contains both ovarian follicles and testicular tubular elements. Ovotesticular disorder of sexual development occurs in fewer than 10% of all disorders of sexual development. Gonadal tumors with malignant potential occur in 2.6% of all cases of ovotesticular disorder of sexual development. Case: Here we represent a 77-year-old woman with primary amenorrhea, infertility and 10cm solid mass in left adnex with 46 XY in karyotype with ovotestis neuroendocrine neoplasm in pathology report which was treated with a multi-modality manner including surgery and chemotherapy but she came back with pulmonary metastasis after 2 cycles of chemotherapy. For women who present with a stage 1 primary ovarian neuroendocrine tumor the prognosis is excellent with greater than 90% survival. Neuroendocrine tumor of the ovary represents 3 % of all neuroendocrine tumors. The prevalence of ovotestis is 1/20000 births. For women with more advanced disease, the prognosis is poor. Neuroendocrine carcinoma of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. The prevalence of ovotestis is 1/20000 births and gonadal malignancies are the most reported neoplasm affected the ovotestis. Here we report a case of ovotestis which is presented with neuroendocrine carcinoma and poor prognosis. Conclusion: Neuroendocrine carcinoma of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. The prevalence of ovotestis is rare and gonadal malignancies are the most reported neoplasm affected the ovotestis. PMID:28066838

  6. Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse

    Directory of Open Access Journals (Sweden)

    Mark S. Nash

    2013-09-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  7. Neuroendocrine and Cardiac Metabolic Dysfunction and NLRP3 Inflammasome Activation in Adipose Tissue and Pancreas following Chronic Spinal Cord Injury in the Mouse

    Directory of Open Access Journals (Sweden)

    Gregory E. Bigford

    2013-08-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immunohistochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  8. The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases

    Directory of Open Access Journals (Sweden)

    Walid E Khalbuss

    2011-01-01

    Full Text Available Background: Small-cell carcinoma (SCC and large-cell neuroendocrine carcinoma (LCNEC are uncommon in serous body cavity effusions. The purpose of this study is to examine the cytomorphological spectrum of SCC and LCNEC in body cavity serous fluids. Materials and Methods: We have 68 cases from 53 patients who had metastatic SCC or LCNEC diagnoses. All cytology slides and the available clinical data, histological follow-up, and ancillary studies were reviewed. Results: A total of 68 cases (60 pleural, 5 peritoneal, and 3 pericardial effusions from 53 patients with an average age of 73 years (age range 43-92 years were reported as diagnostic or suspicious of SCC (52 cases or LCNEC (16 cases. The primary site was lung in 56 cases, pancreas in 6 cases, and 2 cases each from cervix, colon, and the head and neck region. Of the 68 cases, 48 cases had no history of malignancy of the same type. Ancillary studies were used in 46 cases (68% including flow cytometric studies in 5 cases. There were three predominant cytomorphological patterns observed including small-cell clusters with prominent nuclear molding (33 cases, 49%, large-cell clusters mimicking non-small-cell carcinoma (18 cases, 26%, and single-cell pattern mimicking lymphoma (17 cases, 25%. Significant apoptosis was seen in 22 cases (33% and marked tumor cell cannibalism was seen in 11 cases (16%. Nucleoli were prominent in 16 cases (24%. The most frequent neuroendocrine markers performed were synaptophysin and chromogranin. Conclusions: The most common cytomorphologic patterns seen in body cavity effusions of SCC and LCNEC were small-cell clusters with nuclear molding. However, in 51% of the cases either a predominant single-cell pattern mimicking lymphoma or large-cell clusters mimicking non-small carcinoma were noted. In our experience, effusions were the first manifestation of disease in the majority of patients diagnosed with neuroendocrine carcinoma. Therefore, familiarity with the

  9. Endoscopic diagnosis and treatment of pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Rustagi, Tarun; Farrell, James J

    2014-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms comprising only 1% to 2% of all pancreatic tumors. In recent years, the number of incidentally discovered PNETs has greatly increased given the widespread use of axial imaging. However, a significant proportion of PNETs may not be visualized on conventional imaging such as computed tomography, magnetic resonance imaging, and somatostatin receptor scintigraphy. Endoscopic ultrasound (EUS) has become an integral part of the diagnosis of PNETs because of its high sensitivity for detecting, localizing, and diagnosing PNETs. EUS-guided tissue acquisition provides histologic and immunologic confirmation, and may also allow prognostication about tumor behavior. In addition to preoperative assessment of these tumors, EUS has also been shown to have an important role in nonoperative management of small nonfunctional PNETs. Finally, recent developments suggest that interventional EUS may be used to aid intraoperative localization of PNETs and to deliver therapeutic agents for the treatment of PNETs. This review will discuss the endoscopic diagnosis and treatment of PNETs, with focus on recent advances in the utility of EUS in the clinical management of these tumors.

  10. Divergent neuroendocrine responses to localized and systemic inflammation.

    Science.gov (United States)

    Lukewich, Mark K; Rogers, Richard C; Lomax, Alan E

    2014-10-01

    The sympathetic nervous system (SNS) is part of an integrative network that functions to restore homeostasis following injury and infection. The SNS can provide negative feedback control over inflammation through the secretion of catecholamines from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Central autonomic structures receive information regarding the inflammatory status of the body and reflexively modulate SNS activity. However, inflammation and infection can also directly regulate SNS function by peripheral actions on postganglionic cells. The present review discusses how inflammation activates autonomic reflex pathways and compares the effect of localized and systemic inflammation on ACCs and postganglionic sympathetic neurons. Systemic inflammation significantly enhanced catecholamine secretion through an increase in Ca(2+) release from the endoplasmic reticulum. In contrast, acute and chronic GI inflammation reduced voltage-gated Ca(2+) current. Thus it appears that the mechanisms underlying the effects of peripheral and systemic inflammation neuroendocrine function converge on the modulation of intracellular Ca(2+) signaling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Advanced Gastric Neuroendocrine Carcinoma with an Adenocarcinoma Component

    Directory of Open Access Journals (Sweden)

    Masashi Miguchi

    2012-01-01

    Full Text Available In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

  12. 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.)

  13. Neuroendocrine tumors of the gastro-entero-pancreatic system

    Institute of Scientific and Technical Information of China (English)

    Sara Massironi; Valentina Sciola; Maddalena Peracchi; Clorinda Ciafardini; Matilde Pia Spampatti; Dario Conte

    2008-01-01

    Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms,although their prevalence has increased substantially over the past three decades.Moreover,there has been an increased clinical recognition and characterization of these neoplasms.They show extremely variable biological behavior and clinical course.Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes,including carcinoid syndrome; however,many are clinically silent until late presentation with mass effects.Investigation and management should be individualized for each patient,taking into account the likely natural history of the tumor and general health of the patient.Management strategies include surgery for cure or palliation,and a variety of other cytoreductive techniques,and medical treatment including chemotherapy,and biotherapy to control symptoms due to hormone release and tumor growth,with somatostatin analogues (SSAs) and alphainterferon.New biological agents and somatostatintagged radionuclides are under investigation.Advances in the therapy and development of centers of excellence which coordinate multicenter studies,are needed to improve diagnosis,treatment and therefore survival of patients with GEP NETs.(C)2008 The WIG Press.All rights reserved.

  14. Whole-genome landscape of pancreatic neuroendocrine tumours.

    Science.gov (United States)

    Scarpa, Aldo; Chang, David K; Nones, Katia; Corbo, Vincenzo; Patch, Ann-Marie; Bailey, Peter; Lawlor, Rita T; Johns, Amber L; Miller, David K; Mafficini, Andrea; Rusev, Borislav; Scardoni, Maria; Antonello, Davide; Barbi, Stefano; Sikora, Katarzyna O; Cingarlini, Sara; Vicentini, Caterina; McKay, Skye; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; McLean, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wilson, Peter J; Anderson, Matthew J; Fink, J Lynn; Newell, Felicity; Waddell, Nick; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Wood, Scott; Xu, Qinying; Nagaraj, Shivashankar Hiriyur; Amato, Eliana; Dalai, Irene; Bersani, Samantha; Cataldo, Ivana; Dei Tos, Angelo P; Capelli, Paola; Davì, Maria Vittoria; Landoni, Luca; Malpaga, Anna; Miotto, Marco; Whitehall, Vicki L J; Leggett, Barbara A; Harris, Janelle L; Harris, Jonathan; Jones, Marc D; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Nagrial, Adnan M; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia; Rooman, Ilse; Toon, Christopher; Wu, Jianmin; Pinese, Mark; Cowley, Mark; Barbour, Andrew; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Lovell, Jessica A; Jamieson, Nigel B; Duthie, Fraser; Gingras, Marie-Claude; Fisher, William E; Dagg, Rebecca A; Lau, Loretta M S; Lee, Michael; Pickett, Hilda A; Reddel, Roger R; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Epari, Krishna; Nguyen, Nam Q; Zeps, Nikolajs; Falconi, Massimo; Simbolo, Michele; Butturini, Giovanni; Van Buren, George; Partelli, Stefano; Fassan, Matteo; Khanna, Kum Kum; Gill, Anthony J; Wheeler, David A; Gibbs, Richard A; Musgrove, Elizabeth A; Bassi, Claudio; Tortora, Giampaolo; Pederzoli, Paolo; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2017-03-02

    The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

  15. Primary infertility associated with neuroendocrine tumor (Carcinoid) of the appendix

    Institute of Scientific and Technical Information of China (English)

    Brad B Swelstad; Paul R Brezina; Clark T Johnson; Nina Resetkova; Irene Woo; Lisa Kolp

    2012-01-01

    Neuroendocrine tumors of the appendix(NET-A), formerly called appendiceal carcinoids, are rare tumors of the gastrointestinal tract.Appendiceal tumors have also been associated with infertility. However, in many of these cases, significant abdominal pathology, specifically pseudomyxoma peritonei, was identified during definitive surgical intervention.A34-year-old nulligravid woman undergoing infertility evaluation presented to an academic tertiary care fertility center. An abnormal mass was identified on hysterosalpingogram andCT confirmed appendiceal mass. Surgical removal of the mass was performed and histopathology was consistent with anNET-A with negative margins extending to the serosa.Two months after surgical intervention, the patient spontaneously conceived pregnancy and subsequently delivered a normal infant.This case exemplifies the importance of careful inspection of radiologic films by the gynecologic physician. Of added interest, this case describes an asymptomaticNET-A associated with primary infertility. To our knowledge, this is the first report of an incidentally indentifiedNET-A that resulted in primary infertility.

  16. Neuroendocrine control of physiological color change in Chameleo gracilis.

    Science.gov (United States)

    Okelo, O

    1986-11-01

    Color changes in Chameleo gracilis are under neuroendocrine control. Denervation of the limbs, by removal of the sciatic or brachial nerves, does not interfere with the normal color changes in the affected limbs. Denervated skins, placed back onto C. gracilis, show color changes in synchrony with the rest of the animal. Pieces of isolated skin turn very dark or black in alpha-melanophore stimulating hormone (alpha-MSH) and green in adrenaline, but do not show any color changes in physiological saline. Hypophysectomized animals turn green but never turn dark. Injections of alpha-MSH cause intact or hypophysectomized animals to turn dark or black, while injections of adrenaline cause them to turn light green. Injections of physiological saline have no effect. Crude pituitary extracts cause darkening of isolated skins or of intact animals injected with such extracts. Similar treatment with crude extracts of adrenal glands causes the skins to become light green. Electrical stimulation of transected spinal cord leads to localized lightening of the skin but never to darkening of the same. Light, temperature, darkness, and color of the surroundings influence color change. Color change to green at night and to darker colors in the daytime suggests a possible circadian rhythm in the phenomenon.

  17. Peptide receptor radionuclide therapy: focus on bronchial neuroendocrine tumors.

    Science.gov (United States)

    Lo Russo, Giuseppe; Pusceddu, Sara; Prinzi, Natalie; Imbimbo, Martina; Proto, Claudia; Signorelli, Diego; Vitali, Milena; Ganzinelli, Monica; Maccauro, Marco; Buzzoni, Roberto; Seregni, Ettore; de Braud, Filippo; Garassino, Marina Chiara

    2016-10-01

    Well-differentiated bronchial neuroendocrine tumors (B-NETs) are rare. They represent 1-5 % of all lung cancers. The incidence of these neoplasms has risen over the past 30 years and, especially for advanced or metastatic disease, management is complex and requires a multidisciplinary approach. Treatment with somatostatin analogs (SSAs) is the most important first-line therapy, in particular in well-differentiated NETs with high somatostatin type receptor (SSTR) expression. In these tumors, the role of mammalian target of rapamycin (m-TOR) inhibitors and the potential utility of other target therapies remain unclear while chemotherapy represents the gold standard treatment only for aggressive forms with low SSTR expression. Peptide receptor radionuclide therapy (PRRT) is an emerging treatment modality for advanced NETs. There are many cumulative evidences about the effectiveness and tolerability of this therapeutic approach, especially in gastro-entero-pancreatic (GEP)-NETs. For B-NETs, scientific research is moving more slowly. Here, we performed a review in order to evaluate the efficacy and toxicity of PRRT with a focus on patients with inoperable or metastatic well-differentiated B-NETs.

  18. Lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Saif, Muhammad Wasif

    2016-01-01

    The prevalence of gastropancreatic neuroendocrine tumors (GEP-NETs), a largely sporadically occurring group of neoplasms, has rapidly increased. NET diagnoses often occur late and entail treatment challenges; treatment beyond surgical resection is typically required. Somatostatin analogs (SSAs), the cornerstone of GEP-NET therapy, target somatostatin receptors on NET cell surfaces and can ameliorate NET-related symptoms and prevent tumor progression. This expert review summarizes the development of the SSA lanreotide and its role in treating NETs. Key lanreotide preclinical and clinical findings in acromegaly, carcinoid syndrome, and NETs are discussed, along with future treatment goals and therapeutic prospects. The role of SSAs in NET treatment was historically one of symptom management. Although this is a critical therapeutic component, ideal treatment would include prevention of tumor progression. As GEP-NETs are biologically diverse, progression prevention can be difficult, depending on primary tumor site and functional status. Recent data indicate that lanreotide significantly prolonged progression-free survival in metastatic GEP-NET patients. Practice patterns seem to be shifting toward using SSAs as first-line therapy. Response to SSAs has typically been categorized as either symptomatic or biochemical. However, SSA use to prevent tumor progression will lead to a new, objective response category based on tumor growth.

  19. Hepatic arterial embolization in patients with neuroendocrine tumors

    Science.gov (United States)

    2014-01-01

    Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient’s quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques. TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases. PMID:24887262

  20. 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.)

  1. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models?

    Science.gov (United States)

    Veenema, Alexa H

    2009-10-01

    Early life stress (child and adolescent abuse, neglect and trauma) induces robust alterations in emotional and social functioning resulting in enhanced risk for the development of psychopathologies such as mood and aggressive disorders. Here, an overview is given on recent findings in primate and rodent models of early life stress, demonstrating that chronic deprivation of early maternal care as well as chronic deprivation of early physical interactions with peers are profound risk factors for the development of inappropriate aggressive behaviors. Alterations in the hypothalamic-pituitary-adrenocortical (HPA), vasopressin and serotonin systems and their relevance for the regulation of aggression are discussed. Data suggest that social deprivation-induced inappropriate forms of aggression are associated with high or low HPA axis (re)activity and a generally lower functioning of the serotonin system in adulthood. Moreover, genetic and epigenetic modifications in HPA and serotonin systems influence the outcome of early life stress and may even moderate adverse effects of early social deprivation on aggression. A more comprehensive study of aggression, neuroendocrine, neurobiological and (epi)genetic correlates of early life stress using animal models is necessary to provide a better understanding of the invasive aggressive deficits observed in humans exposed to child maltreatment.

  2. A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas.

    Science.gov (United States)

    Tang, Laura H; Basturk, Olca; Sue, Jillian J; Klimstra, David S

    2016-09-01

    WHO G1/G2 components, or there had been a prior established diagnosis of a primary WD-NET, the final diagnosis was rendered as a WD-NET with high-grade (G3) progression. If a component of conventional adenocarcinoma was present (in slides not seen in the initial review), the diagnosis was established as a combined adenocarcinoma and PD-NEC. All 3 pathologists agreed on the morphologic classification of 33% of the cases (6 WD-NET, 3 PD-NEC-SCC, and 2 PD-NEC-LCC), were conflicted on 2 cases between PD-NEC-SCC and PD-NEC-LCC, and disagreed or were uncertain on the classification for the remaining 20 cases (61%), which were therefore categorized as ambiguous. In the group of cases in which all pathologists agreed on the classification, the 6 WD-NET cases had either loss of DAXX or ATRX or had evidence of a WD-NET based on additional or prior pathology slides. The 7 PD-NEC cases had abnormal expression of p53, Rb, and/or SMAD4 or a coexisting adenocarcinoma. In the ambiguous group (n=20), 14 cases were established as WD-NETs, based upon loss of DAXX or ATRX in 7 cases and additional pathology evidence of high-grade progression from WD-NET in the other 7 cases; 5 cases were established as PD-NEC based upon abnormal expression of p53, Rb, and/or SMAD4; 1 case remained undetermined with normal expression of all markers and no evidence of entity-defining histologic findings in other slides. On the basis of the final pathologic classifications, the disease-specific survival was 75 and 11 months for the WD-NET and PD-NEC groups, respectively. Thus, we conclude that morphologic diagnosis of high-grade pancreatic neuroendocrine neoplasms is challenging, especially when limited pathologic materials are available, and necessitates better defined criteria. The analysis of both additional sections and prior material, along with an immunohistochemical evaluation, can facilitate accurate diagnosis in the majority of cases and guide the appropriate clinical management and prognosis.

  3. [Does neuroendocrine differentiation have prognostic value in prostate core needle biopsies?].

    Science.gov (United States)

    Jaskulski, Jarosław; Gołabek, Tomasz; Kopczyński, Janusz; Orłowsk, Pawel; Bukowczan, Jakub; Dudek, Przemek; Chłosta, Piotr

    2013-01-01

    The biological behaviour of prostate cancer (PCa) varies significantly and cannot be, therefore, predicted. Better understanding of the mechanisms underpinning PCa oncogenesis and progression with its yet-to-be discovered poor prognostic factors is essential in order to optimise and tailor treatment to an individual patient. The aim of this paper was to investigate the association between the rate of focal PCa neuroendocrine activity, tumour cell proliferation index score, and the rate of PCa positive core needle biopsy results. 92 men, with histologically confirmed PCa, which was clinically confined to the prostate and was graded with Gleason score > or =7, had their core needle biopsies under transrectal ultrasonography guidance performed. The PCa neuroendocrine activity was immunohistochemically confirmed using antibodies against Chromogranin-A and neuron specific enolase. The neuroendocrine activity was detected in 14 (13%) out of 92 PCa patients participating in the study. The proliferative index was not increased in non-cancerous prostate cells. There was no relationship between PCa neuroendocrine activity, the number and percentage of PCa positive biopsies, prostate volume, serum PSA concentration, and Gleason score found. No association between selected PCa prognostic factors and neuroendocrine activity could be found in patients with organ confined prostate cancer.

  4. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

  5. 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.)

  6. The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites.

    Science.gov (United States)

    Ly, Thai Yen; Walsh, Noreen M; Pasternak, Sylvia

    2012-04-01

    Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with

  7. Identification of Prostate Cancer Prognostic Markers

    Science.gov (United States)

    2015-10-01

    targets. Specific aims are: 1) To profile bone metastasis samples to identify genomic alterations of PCa metastases that can be retrieved in their...Current markers - preoperative serum prostate specific antigen (PSA) levels, tumor stage and biopsy Gleason score (GS) - cannot accurately predict...individual patient outcome. For advanced and metastatic disease there is no curative treatment. Genomic profiling studies have identified specific genomic

  8. The relation between work-induced neuroendocrine reactivity and recovery, subjective need for recovery, and health status

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF

    Objectives: The purpose of this cross-sectional study with repeated measurements was to find out to what extent neuroendocrine reactivity during work and neuroendocrine recovery from work, and work characteristics, are related to subjective need for recovery and perceived health status. Methods:

  9. Ceramic subsurface marker prototypes

    Energy Technology Data Exchange (ETDEWEB)

    Lukens, C.E. [Rockwell International Corp., Richland, WA (United States). Rockwell Hanford Operations

    1985-05-02

    The client submitted 5 sets of porcelain and stoneware subsurface (radioactive site) marker prototypes (31 markers each set). The following were determined: compressive strength, thermal shock resistance, thermal crazing resistance, alkali resistance, color retention, and chemical resistance.

  10. liver function markers and associated serum electrolytes changes in ...

    African Journals Online (AJOL)

    2013-09-09

    Sep 9, 2013 ... Results: Serum liver function markers were significantly altered in HIV infected individuals compared ... correlated with protein levels (r = 0.917) and vice versa. .... hypertension, diabetes or alcohol abuse or history of jaundice ...

  11. The neuroendocrine system and stress, emotions, thoughts and feelings

    Directory of Open Access Journals (Sweden)

    Vaillant George

    2011-01-01

    Full Text Available The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions, and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain" terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct or agape (noble, non-specific valuing of all other people miss the motivational forest for the trees. Neither Eros (hypothalamic nor agape (cortical has a fraction of the power to relieve stress as attachment (limbic love, yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  12. The neuroendocrine system and stress, emotions, thoughts and feelings

    Directory of Open Access Journals (Sweden)

    George E. Vaillant

    2011-03-01

    Full Text Available The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions, and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain" terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct or agape (noble, non-specific valuing of all other people miss the motivational forest for the trees. Neither Eros (hypothalamic nor agape (cortical has a fraction of the power to relieve stress as attachment (limbic love, yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  13. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

  14. Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine tumors.

    Science.gov (United States)

    Gincul, Rodica; Ponchon, Thierry; Napoleon, Bertrand; Scoazec, Jean-Yves; Guillaud, Olivier; Saurin, Jean-Christophe; Ciocirlan, Mihai; Lepilliez, Vincent; Pioche, Mathieu; Lefort, Christine; Adham, Mustapha; Pialat, Jean; Chayvialle, Jean-Alain; Walter, Thomas

    2016-11-01

    Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk.

  15. Factors Associated with Survival of Veterans with Gastrointestinal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Bryan L. Balmadrid

    2012-01-01

    Full Text Available Background. Gastrointestinal (GI neuroendocrine tumor (NET incidence has been increasing; however, GI NET within the national Veterans Affairs (VA health system has not been described. Methods. We used the VA Central Cancer Registry to identify the cohort of patients diagnosed with GI NET in 1995–2009. Cox regression models were constructed to explore factors associated with survival. Results. We included 1793 patients with NET of the stomach (9%, duodenum (10%, small intestine (24%, colon (19% or rectum (38%. Twenty percent were diagnosed in 1995–1999, 35% in 2000–2004, and 45% in 2005–2009. Unadjusted 5-year survival rates were: stomach 56%, duodenum 66%, small intestine 52%, colon 67%, and rectum 84%. Factors associated with shorter survival were increasing age, hazard ratio (HR 1.05 (95% CI 1.04–1.06, NET location [compared to rectum: stomach HR 2.26 (95% CI 1.68–3.05, duodenum HR 1.70 (95% CI 1.26–2.28, small intestine HR 1.85 (95% CI 1.42–2.42, and colon 1.83 (95% CI 1.41–2.39], stage [compared to in situ/local: regional HR 1.15 (95% CI 0.90–1.47, distant HR 2.38 (95% CI 1.87–3.05], and earlier period of diagnosis [compared to 1995–1999: 2000–2004 HR 0.70 (95% CI 0.59–0.85, 2005–2009 HR 0.43 (95% CI 0.34–0.54]. Conclusions. The incidence of GI NET has also increased over time in the VA system with similar survival rates to those observed in non-VA settings. Worsened survival was associated with older age, tumor site, advanced stage, and earlier year of diagnosis.

  16. Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada; Hirotoshi Maruo

    2011-01-01

    A large cell neuroendocrine carcinoma (LCNEC) of the stomach is very rare. A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea. Endoscopy revealed 2 large tumors in the stomach. He did not have multiple endocrine neoplasia type Ⅰ or Zollinger-Ellison syndrome. Imaging modali-ties, including computed tomography and magnetic resonance imaging, revealed no other tumors. Gas-trectomy, cholecystectomy, and lymph node dissection were performed. The resected stomach had 2 tumors: one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm, and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus. Micro-scopically, the antral ulcerated tumor was a well differ-entiated adenocarcinoma with deep invasion. The fun-dus polypoid tumor was a LCNEC, being composed of malignant large cells arranged in trabecular and nested patterns. The tumor cells were large and the nuclei were vesicular. Nucleoli were frequently present, and there were many mitotic figures, apoptotic bodies, and necrotic areas. Much lymphovascular permeation was seen. Seven out of 29 dissected lymph nodes showed metastatic foci; 6 were from the LCNEC and 1 from the adenocarcinoma. Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes. Mucins were present in the adenocarcinoma but not in the LCNEC. Immunohistochemically, the LCNEC tumor cells were positive for pancytokeratins, synaptophysin (50% positive), chromogranin A (10% positive), Ki-67 (90% labeled), and platelet-derived growth factor-α (80% positive). They were negative for KIT, p53, CD56, and neuron-specific enolase. The non-cancerous stomach showed a normal number of endocrine cells. The patient is now treated with adju-vant chemotherapy.

  17. Lanreotide Depot: An Antineoplastic Treatment of Carcinoid or Neuroendocrine Tumors.

    Science.gov (United States)

    Wolin, Edward M; Manon, Amandine; Chassaing, Christophe; Lewis, Andy; Bertocchi, Laurent; Richard, Joel; Phan, Alexandria T

    2016-12-01

    Peptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europe for symptom control in carcinoid syndrome associated with GEP-NETs. This review discusses how the distinct molecule and formulation of lanreotide depot provide advantages to patients and health care providers, as well as the most recent clinical evidence demonstrating the safety and efficacy of lanreotide depot in inhibiting tumor growth and controlling hormonal symptoms in GEP-NETs. The lanreotide depot formulation confers a remarkable pharmacokinetic profile with no excipients, comprised only of lanreotide acetate and water. Of note, lanreotide depot constitutes an example for peptide self-assembly based formulations, providing insights that could help future development of sustained-release formulations of other antineoplastic peptides. Most patients with GEP-NETs will present with inoperable or incurable disease; thus, medical management for symptoms and tumor control plays a crucial role. Recent long-term clinical studies have demonstrated that lanreotide depot is well tolerated, prolongs PFS in GEP-NET patients, and significantly reduces symptoms related to carcinoid syndrome. The unique depot formulation and delivery method of lanreotide confer advantages in the treatment of metastatic GEP-NETs, contributing to improvements in NET-related symptoms and PFS without reducing quality of life in this patient population.

  18. AMPK and the neuroendocrine regulation of appetite and energy expenditure.

    Science.gov (United States)

    Stark, Romana; Ashley, Sarah E; Andrews, Zane B

    2013-02-25

    This review highlights recent advances in the hormonal control of hypothalamic AMPK activity and the impact on appetite and energy metabolism. AMPK is an intracellular energy sensor that switches off ATP-consuming pathways and switches on ATP-producing pathways such as glucose uptake and fatty acid oxidation. In this regard, it is well positioned to respond to dynamic changes in metabolic state and nutritional over- or under-supply. Within the hypothalamus, AMPK responds to peripheral hormones that convey metabolic information based on increased plasma concentrations. For example, negative energy balance increases plasma ghrelin concentrations, increases hypothalamic AMPK and drives food intake. Conversely, plasma leptin concentrations are secreted in proportion to adipose levels and leptin suppresses hypothalamic AMPK activity and restricts food intake. This review explains that hypothalamic AMPK mediates neuroendocrine feedback control of energy metabolism. A current working model suggests that endocrine feedback influences hypothalamic AMPK via a number of mechanisms designed to shift an organism from negative to neutral energy balance. These mechanisms include (1) ghrelin stimulation of AMPK in NPY/AgRP in the arcuate nucleus (2) ghrelin stimulation of AMPK in the ventromedial hypothalamic nucleus, (3) a novel ghrelin-stimulated AMPK-dependent presynaptic mechanism that sustains AgRP neuron firing via a local synaptic memory system, (4) adiponectin stimulation of hypothalamic AMPK and (5) hypothalamic AMPK control of energy expenditure by thyroid hormone or leptin. The number of diverse mechanisms ensures hypothalamic AMPK drives the shift from negative to neutral energy balance and underscores the fundamental importance of hypothalamic AMPK to maintain neutral energy balance. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. The neuroendocrine system and stress, emotions, thoughts and feelings.

    Science.gov (United States)

    Vaillant, George E

    2011-01-01

    The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain") terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  20. Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

    Science.gov (United States)

    Kotteas, Elias A; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2016-01-01

    Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. PMID:26929640

  1. Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms.

    Science.gov (United States)

    Yang, Grace C H

    2016-01-01

    This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow-up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high-grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module.

  2. [Neuroendocrine carcinoma with large cells of the breast: case report and review of the literature].

    Science.gov (United States)

    Bourhaleb, Z; Uri, N; Haddad, H; Azzouzi, S; Zamiati, S; Benchakroun, N; Tawfiq, N; Jouhadi, H; Sahraoui, S; Benider, A

    2009-12-01

    Neuroendocrine carcinoma with large cells is a slightly different tumor from the high rank of malignity. We report a case of breast localization in a 28-year-old patient. It is a locally advanced classified T4dN1M0 tumor that required neoadjuvant chemotherapy. The clinical answer was 75% of the level of the tumor. A standard surgery mastectomy with axillary lymph node dissection was realized, followed by external radiotherapy. The anatomopathologic and the immuno-histochemical study of the operational part confirmed the diagnosis of neuroendocrine carcinoma with large cells expressing the progesterone receptor. The patient is subjected to adjuvant hormonal treatment. After a 12 months retreat, a complete remission is maintained. Considering the scarcity of neuroendocrine carcinoma with large cells of the breast, the therapeutic standard is not yet available and the forecast remains difficult to determine.

  3. 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

  4. 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......-line treatment in small cell lung cancer, which also responds markedly on first-line platin/etoposide. Hence, we investigated the feasibility of topotecan in previously treated patients with neuroendocrine carcinomas. MATERIAL AND METHODS: Retrospective analysis of 22 patients with disseminated and progressive...... 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...

  5. 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

    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...... not support the advice for HF patients to restrict dietary sodium.......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...... 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...

  6. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Norsk, Peter; Gustafsson, Finn

    2006-01-01

    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...... not support the advice for HF patients to restrict dietary sodium.......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...... 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...

  7. Adulthood stress responses in rats are variably altered as a factor of adolescent stress exposure.

    Science.gov (United States)

    Moore, Nicole L T; Altman, Daniel E; Gauchan, Sangeeta; Genovese, Raymond F

    2016-05-01

    Stress exposure during development may influence adulthood stress response severity. The present study investigates persisting effects of two adolescent stressors upon adulthood response to predator exposure (PE). Rats were exposed to underwater trauma (UWT) or PE during adolescence, then to PE after reaching adulthood. Rats were then exposed to predator odor (PO) to test responses to predator cues alone. Behavioral and neuroendocrine assessments were conducted to determine acute effects of each stress experience. Adolescent stress altered behavioral response to adulthood PE. Acoustic startle response was blunted. Bidirectional changes in plus maze exploration were revealed as a factor of adolescent stress type. Neuroendocrine response magnitude did not predict severity of adolescent or adult stress response, suggesting that different adolescent stress events may differentially alter developmental outcomes regardless of acute behavioral or neuroendocrine response. We report that exposure to two different stressors in adolescence may differentially affect stress response outcomes in adulthood. Acute response to an adolescent stressor may not be consistent across all stressors or all dependent measures, and may not predict alterations in developmental outcomes pertaining to adulthood stress exposure. Further studies are needed to characterize factors underlying long-term effects of a developmental stressor.

  8. 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.

  9. Neuroendocrine-immune system interactions in amphibians: implications for understanding global amphibian declines.

    Science.gov (United States)

    Rollins-Smith, L A

    2001-01-01

    Amphibians are ancient creatures valued by biologists and naturalists around the world. They share with all other vertebrates a complex neuroendocrine system that enables them to flourish in a variety of aquatic and semiaquatic environments. Studies from a number of laboratories have demonstrated that the immune system of amphibian species is nearly as complex as that of mammals. Yet for reasons that are not well understood, amphibian species are facing greater survival challenges than in the recent past. This article will review our current understanding of the neuroendocrine immune system interactions in amphibians and address the question of whether environmental stressors may contribute to immunosuppression and amphibian declines.

  10. Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

    Institute of Scientific and Technical Information of China (English)

    Ji-Hong Sun; Ming Chao; Shi-Zheng Zhang; Guang-Qiang Zhang; Bin Li; Jian-Jun Wu

    2008-01-01

    Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT)and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

  11. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

    Institute of Scientific and Technical Information of China (English)

    Daniel Kaemmerer; Vikas Prasad; Wolfgang Daffner; Dieter H(o)rsch; Günter Kl(o)ppel; Merten Hommann; Richard P Baum

    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.

  12. 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

  13. Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type.

    Science.gov (United States)

    Pelosi, Giuseppe; Sonzogni, Angelica; Galetta, Domenico; Perrone, Federica; Braidotti, Paola; Manzotti, Michela; Fabbri, Alessandra; Spaggiari, Lorenzo; Veronesi, Giulia; Viale, Giuseppe

    2011-04-01

    The combined variant of small-cell lung carcinoma (SCLC) refers to the variable admixture of small cell and non-small cell carcinoma, whereas the association with sarcoma or sarcoma-like elements is exceedingly rare. A 76-year-old Caucasian man underwent right upper lobectomy with regional lymphadenectomy because of a symptomatic 7 cm-sized tumor mass. Formalin fixed-paraffin embedded material was used to highlight several differentiation cell lineages by means of immunohistochemistry, electron microscopy, and mutational assay. The tumor was discovered as being IIB stage (pT2b pN1(1/51) pM0) and featured biphasic appearance with close intermingling of SCLC (40%) and collagen-rich spindle cell sarcoma (60%). Epithelial (cytokeratins, TTF-1), neural (neurofilaments, GFAP), endocrine (chromogranin, synaptophysin, CD56), and skeletal muscle (desmin, sarcomeric actin, myogenin) markers were variably co-expressed by SCLC elements, whereas mesenchymal (vimentin), smooth muscle (actin, myosin, H-caldesmon, calponin), fibroblastic (CD10), and, more focally, skeletal muscle (desmin, sarcomeric actin and myogenin) markers were highlighted in the spindle cell sarcoma elements. TP53 codon V274F mutation in exon 8 was shared by either cell component. After undergoing adjuvant chemotherapy, the patient is currently alive and well at the 40-month follow-up. To the best of our knowledge, this is the first report of combined SCLC with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type, somewhere at the level of the same individual tumor cells. This tumor had probably derived for clonal evolution of a p53-mutated common ancestor lesion.

  14. The prognostic and predictive value of sstr{sub 2}-immunohistochemistry and sstr{sub 2}-targeted imaging in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Philippe [University Hospital Basel, Institute of Pathology (Switzerland); University Hospital Basel, Institute of Nuclear Medicine (Switzerland); Joerg, Ann-Catherine; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine (Switzerland); Glatz, Katharina; Bubendorf, Lukas [University Hospital Basel, Institute of Pathology (Switzerland); Radojewski, Piotr; Umlauft, Maria; Spanjol, Petar-Marko; Krause, Thomas; Dumont, Rebecca A.; Walter, Martin A. [University Hospital Bern, Institute of Nuclear Medicine (Switzerland); Marincek, Nicolas [University Hospital Basel, Institute of Nuclear Medicine (Switzerland); University Hospital Bern, Institute of Nuclear Medicine (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry (Switzerland); Briel, Matthias [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schmitt, Anja; Perren, Aurel [University Bern, Institute of Pathology, Bern (Switzerland)

    2017-03-15

    Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr{sub 2}) in neuroendocrine tumors (NETs). We established a tissue microarray and imaging database from NET patients that received sstr{sub 2}-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr{sub 2}-imaging and sstr{sub 2}-immunohistochemistry. We included a total of 279 patients. In these patients, sstr{sub 2}-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr{sub 2}-expression on immunohistochemistry correlated with tumor uptake on sstr{sub 2}-imaging (n = 170, p < 0.001); however, sstr{sub 2}-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 - 56 %, p = 0.025). Sstr{sub 2}-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93). Our results suggest sstr{sub 2} as an independent prognostic marker in NETs. Sstr{sub 2}-immunohistochemistry correlates with sstr{sub 2}-imaging; however, sstr{sub 2}-imaging is more accurate for determining the individual prognosis. (orig.)

  15. Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography in patients with gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma.

    Science.gov (United States)

    Lim, Sun Min; Kim, Hyunki; Kang, Beodeul; Kim, Hyo Song; Rha, Sun Young; Noh, Sung Hoon; Hyung, Woo Jin; Cheong, Jae-Ho; Kim, Hyoung-Il; Chung, Hyun Cheol; Yun, Mijin; Cho, Arthur; Jung, Minkyu

    2016-05-01

    Gastric neuroendocrine carcinomas (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) are very rare, aggressive tumors of the stomach. We aimed to examine predictive role of pretreatment (18)F-FDG PET/CT-assessed metabolic parameter of primary tumors and metastases in patients with gastric NEC and MANEC. We conducted a review of the 27 patients with histopathologically confirmed NECs (n = 10) and MANEC (n = 17) of the stomach at our institution between January 2005 and December 2012. All patients underwent (18)F-FDG-PET examination at diagnosis. Metabolic parameters [SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] of the primary tumor and metastases on baseline PET/CT were analyzed. The median follow-up duration was 39.4 months (95 % CI 20.0-58.1 months) and the median overall survival (OS) was 25.7 months (95 % CI 14.1-37.2 months). All gastric lesions were well visualized (average SUVmax = 12.0, range 3.0-41.8). When subjects were divided into two groups by ROC cut-off value of 210.9 and 612, patients with high TLG in primary lesion and metastases showed poorer prognosis compared to low TLG patients (P = 0.09, P = 0.002, respectively). In the sub-analysis of patients with metastasis (n = 12), patients with high TLG in whole body tumor showed significantly shorter OS compared to those with low TLG (31.7 ± 11.4 vs. 7.2 ± 2.1 months, P = 0.006). (18)F-FDG PET/CT is useful in evaluating prognosis of advanced gastric cancer with neuroendocrine carcinoma components. Baseline MTV of primary gastric cancer with metastatic disease, and MTV, TLG of metastases may be prognostic markers in patients with gastric NEC and MANEC.

  16. Autophagy pathway is required for IL-6 induced neuroendocrine differentiation and chemoresistance of prostate cancer LNCaP cells.

    Directory of Open Access Journals (Sweden)

    Pei-Ching Chang

    Full Text Available Prostate cancer (PCa cells undergoing neuroendocrine differentiation (NED are clinically relevant to the development of relapsed castration-resistant PCa. Increasing evidences show that autophagy involves in the development of neuroendocrine (NE tumors, including PCa. To clarify the effect of autophagy on NED, androgen-sensitive PCa LNCaP cells were examined. Treatment of LNCaP cells with IL-6 resulted in an induction of autophagy. In the absence of androgen, IL-6 caused an even stronger activation of autophagy. Similar result was identified in NED induction. Inhibition of autophagy with chloroquine (CQ markedly decreased NED. This observation was confirmed by beclin1 and Atg5 silencing experiments. Further supporting the role of autophagy in NED, we found that LC3 was up-regulated in PCa tissue that had relapsed after androgen-deprivation therapy when compared with their primary tumor counterpart. LC3 staining in relapsed PCa tissue showed punctate pattern similar to the staining of chromogranin A (CgA, a marker for NED cells. Moreover, autophagy inhibition induced the apoptosis of IL-6 induced NE differentiated PCa cells. Consistently, inhibition of autophagy by knockdown of beclin1 or Atg5 sensitized NE differentiated LNCaP cells to etoposide, a chemotherapy drug. To identify the mechanisms, phosphorylation of IL-6 downstream targets was analyzed. An increase in phospho-AMPK and a decrease in phospho-mTOR were found, which implies that IL-6 regulates autophagy through the AMPK/mTOR pathway. Most important to this study is the discovery of REST, a neuronal gene-specific transcriptional repressor that is involved in autophagy activation. REST was down-regulated in IL-6 treatment. Knockdown experiments suggest that REST is critical to NED and autophagy activation by IL-6. Together, our studies imply that autophagy is involved in PCa progression and plays a cytoprotective role when NED is induced in PCa cells by IL-6 treatment. These results

  17. Autophagy Pathway Is Required for IL-6 Induced Neuroendocrine Differentiation and Chemoresistance of Prostate Cancer LNCaP Cells

    Science.gov (United States)

    Chang, Yi-Ting; Chu, Cheng-Ying; Lee, Chin-Ling; Hsu, Hung-Wei; Zhou, Tyng-An; Wu, Zhaoju; Kim, Randie H.; Desai, Sonal J.; Liu, Shangqin; Kung, Hsing-Jien

    2014-01-01

    Prostate cancer (PCa) cells undergoing neuroendocrine differentiation (NED) are clinically relevant to the development of relapsed castration-resistant PCa. Increasing evidences show that autophagy involves in the development of neuroendocrine (NE) tumors, including PCa. To clarify the effect of autophagy on NED, androgen-sensitive PCa LNCaP cells were examined. Treatment of LNCaP cells with IL-6 resulted in an induction of autophagy. In the absence of androgen, IL-6 caused an even stronger activation of autophagy. Similar result was identified in NED induction. Inhibition of autophagy with chloroquine (CQ) markedly decreased NED. This observation was confirmed by beclin1 and Atg5 silencing experiments. Further supporting the role of autophagy in NED, we found that LC3 was up-regulated in PCa tissue that had relapsed after androgen-deprivation therapy when compared with their primary tumor counterpart. LC3 staining in relapsed PCa tissue showed punctate pattern similar to the staining of chromogranin A (CgA), a marker for NED cells. Moreover, autophagy inhibition induced the apoptosis of IL-6 induced NE differentiated PCa cells. Consistently, inhibition of autophagy by knockdown of beclin1 or Atg5 sensitized NE differentiated LNCaP cells to etoposide, a chemotherapy drug. To identify the mechanisms, phosphorylation of IL-6 downstream targets was analyzed. An increase in phospho-AMPK and a decrease in phospho-mTOR were found, which implies that IL-6 regulates autophagy through the AMPK/mTOR pathway. Most important to this study is the discovery of REST, a neuronal gene-specific transcriptional repressor that is involved in autophagy activation. REST was down-regulated in IL-6 treatment. Knockdown experiments suggest that REST is critical to NED and autophagy activation by IL-6. Together, our studies imply that autophagy is involved in PCa progression and plays a cytoprotective role when NED is induced in PCa cells by IL-6 treatment. These results reveal the

  18. Apoptotic markers in protozoan parasites

    Directory of Open Access Journals (Sweden)

    Fasel Nicolas

    2010-11-01

    Full Text Available Abstract The execution of the apoptotic death program in metazoans is characterized by a sequence of morphological and biochemical changes that include cell shrinkage, presentation of phosphatidylserine at the cell surface, mitochondrial alterations, chromatin condensation, nuclear fragmentation, membrane blebbing and the formation of apoptotic bodies. Methodologies for measuring apoptosis are based on these markers. Except for membrane blebbing and formation of apoptotic bodies, all other events have been observed in most protozoan parasites undergoing cell death. However, while techniques exist to detect these markers, they are often optimised for metazoan cells and therefore may not pick up subtle differences between the events occurring in unicellular organisms and multi-cellular organisms. In this review we discuss the markers most frequently used to analyze cell death in protozoan parasites, paying special attention to changes in cell morphology, mitochondrial activity, chromatin structure and plasma membrane structure/permeability. Regarding classical regulators/executors of apoptosis, we have reviewed the present knowledge of caspase-like and nuclease activities.

  19. Apoptotic markers in protozoan parasites.

    Science.gov (United States)

    Jiménez-Ruiz, Antonio; Alzate, Juan Fernando; Macleod, Ewan Thomas; Lüder, Carsten Günter Kurt; Fasel, Nicolas; Hurd, Hilary

    2010-11-09

    The execution of the apoptotic death program in metazoans is characterized by a sequence of morphological and biochemical changes that include cell shrinkage, presentation of phosphatidylserine at the cell surface, mitochondrial alterations, chromatin condensation, nuclear fragmentation, membrane blebbing and the formation of apoptotic bodies. Methodologies for measuring apoptosis are based on these markers. Except for membrane blebbing and formation of apoptotic bodies, all other events have been observed in most protozoan parasites undergoing cell death. However, while techniques exist to detect these markers, they are often optimised for metazoan cells and therefore may not pick up subtle differences between the events occurring in unicellular organisms and multi-cellular organisms.In this review we discuss the markers most frequently used to analyze cell death in protozoan parasites, paying special attention to changes in cell morphology, mitochondrial activity, chromatin structure and plasma membrane structure/permeability. Regarding classical regulators/executors of apoptosis, we have reviewed the present knowledge of caspase-like and nuclease activities.

  20. Computation and brain processes, with special reference to neuroendocrine systems.

    Science.gov (United States)

    Toni, Roberto; Spaletta, Giulia; Casa, Claudia Della; Ravera, Simone; Sandri, Giorgio

    2007-01-01

    The development of neural networks and brain automata has made neuroscientists aware that the performance limits of these brain-like devices lies, at least in part, in their computational power. The computational basis of a. standard cybernetic design, in fact, refers to that of a discrete and finite state machine or Turing Machine (TM). In contrast, it has been suggested that a number of human cerebral activites, from feedback controls up to mental processes, rely on a mixing of both finitary, digital-like and infinitary, continuous-like procedures. Therefore, the central nervous system (CNS) of man would exploit a form of computation going beyond that of a TM. This "non conventional" computation has been called hybrid computation. Some basic structures for hybrid brain computation are believed to be the brain computational maps, in which both Turing-like (digital) computation and continuous (analog) forms of calculus might occur. The cerebral cortex and brain stem appears primary candidate for this processing. However, also neuroendocrine structures like the hypothalamus are believed to exhibit hybrid computional processes, and might give rise to computational maps. Current theories on neural activity, including wiring and volume transmission, neuronal group selection and dynamic evolving models of brain automata, bring fuel to the existence of natural hybrid computation, stressing a cooperation between discrete and continuous forms of communication in the CNS. In addition, the recent advent of neuromorphic chips, like those to restore activity in damaged retina and visual cortex, suggests that assumption of a discrete-continuum polarity in designing biocompatible neural circuitries is crucial for their ensuing performance. In these bionic structures, in fact, a correspondence exists between the original anatomical architecture and synthetic wiring of the chip, resulting in a correspondence between natural and cybernetic neural activity. Thus, chip "form

  1. Terminal and progenitor lineage-survival oncogenes as cancer markers.

    Science.gov (United States)

    Vias, Maria; Ramos-Montoya, Antonio; Mills, Ian G

    2008-11-01

    Tumour classification has traditionally focused on differentiation and cellular morphology, and latterly on the application of genomic approaches. By combining chromatin immunoprecipitation with expression array, it has been possible to identify direct gene targets for transcription factors for nuclear hormone receptors. At the same time, there have been great strides in deriving stem and progenitor cells from tissues. It is therefore timely to propose that pairing the isolation of these cell subpopulations from tissues and tumours with these genomics approaches will reveal conserved gene targets for transcription factors. By focusing on transcription factors (lineage-survival oncogenes) with roles in both organogenesis and tumourigenesis at multiple organ sites, we suggest that this comparative genomics approach will enable developmental biology to be used more fully in relation to understanding tumour progression and will reveal new cancer markers. We focus here on neurogenesis and neuroendocrine differentiation in tumours.

  2. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.

    Science.gov (United States)

    Strassman, R J; Qualls, C R

    1994-02-01

    To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperatu