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Sample records for neuroendocrine tumours transfected

  1. [Drug therapy for neuroendocrine tumours].

    PubMed

    Tóth, Miklós

    2013-09-29

    The author aims to review the established medical treatment options of neuroendocrine tumours, which have expanded greatly in recent years and present the most important aspects to be considered in planning patients' management. Medical treatment is usually considered in advanced stages of these tumours, as well as in cases of hormone overproduction. Somatostatin analogues have been known to be effective in alleviating hormone excess syndromes, especially carcinoid syndrome for the past 25 years. There is a convincing evidence that the somatostatin analogue octreotide is useful as an antitumor agent, at least in well-differentiated small intestinal neuroendocrine tumours and probably also in those of pancreatic origin. Interferons may be also used and the indications for their use may be almost the same. Optimal patient selection is mandatory for the use of cytotoxic chemotherapy. Streptozotocin- and, recently, temozolomide-based chemotherapies should be considered in progressive phases of well differentiated (G1/G2) pancreatic neuroendocrine tumours. A cisplatin-etoposide combination is the first choice for the treatment of G3 neuroendocrine carcinomas of any origin. Recently, the mammalian target of rapamycin inhibitor everolimus and the combined tyrosine kinase inhibitor sunitinib were registered for the treatment of G1/G2 pancreatic neuroendocrine tumours. The most recent drug treatment recommendations and therapeutic algorithms to improve systemic therapy in patients with neuroendocrine tumours are summarized and novel drug candidates with particular potential for future management of these tumours are outlined. PMID:24058101

  2. Consensus on biomarkers for neuroendocrine tumour disease

    PubMed Central

    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

  3. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    PubMed

    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. PMID:26971847

  4. Familial syndromes associated with neuroendocrine tumours

    PubMed Central

    Komarowska, Hanna; Czarnywojtek, Agata; Waligórska-Stachura, Joanna; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Neuroendocrine tumours may be associated with familial syndromes. At least eight inherited syndromes predisposing to endocrine neoplasia have been identified. Two of these are considered to be major factors predisposing to benign and malignant endocrine tumours, designated multiple endocrine neoplasia type 1 and type 2 (MEN1 and MEN2). Five other autosomal dominant diseases show more heterogeneous clinical patterns, such as the Carney complex, hyperparathyroidism-jaw tumour syndrome, Von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1) and tuberous sclerosis. The molecular and cellular interactions underlying the development of most endocrine cells and related organs represent one of the more complex pathways not yet to be deciphered. Almost all endocrine cells are derived from the endoderm and neuroectoderm. It is suggested that within the first few weeks of human development there are complex interactions between, firstly, the major genes involved in the initiation of progenitor-cell differentiation, secondly, factors secreted by the surrounding mesenchyme, and thirdly, a series of genes controlling cell differentiation, proliferation and migration. Together these represent a formula for the harmonious development of endocrine glands and tissue. PMID:26557756

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

    PubMed Central

    Das, Anirban; Pratap, Abhishek

    2016-01-01

    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. PMID:27034865

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

    PubMed

    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. PMID:26971840

  7. [Multifocal Pulmonary Neuroendocrine Tumours: Genesis, Diagnostics and Treatment].

    PubMed

    Kirschbaum, A; Beutel, B; Rinke, A; Rexin, P; Fink, L; Koczulla, R; Bartsch, D K

    2016-02-01

    Multifocal neuroendocrine lung tumour is a rare diagnosis. Multiple lung foci of different sizes are usually apparent on chest CT scans. It is assumed that multifocal neuroendocrine lung tumours originally develop from diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). This results in cell aggregations formed by proliferation of neuroendocrine cells that are already physiologically present in the bronchial system. If these cell proliferations break through the bronchial basement membrane, they are considered to constitute tumourlets if they measure ≤ 5 mm and carcinoid tumours if they are larger than 5 mm. The speed of proliferation of the cell hyperplasias appears to vary. Many of the patients are completely asymptomatic, the multifocal neuroendocrine lung tumours being diagnosed by chance. However, other patients complain of breathlessness, reduced physical capacity and cough. There may also be reduction of lung function. In these cases, chest HRCT often reveals peribronchial fibrosis or bronchiectasis in addition to the lung foci. Bronchoscopy is usually not helpful. Surgical lung biopsy is considered to be the diagnostic gold standard. Histological examination typically shows a mixture of cell hyperplasias, tumourlets and carcinoid tumours. There is no consensus on the treatment of multifocal neuroendocrine tumours. Taking the clinical situation and the chest HRCT findings as our starting point, we developed a stepwise approach that is guided by the success of the individual therapeutic procedures. The most favourable prognosis is found in affected people without clinical symptoms whose lung foci all measure less than 5 mm. In these cases the 5-year survival rate is over 90 %. PMID:26894394

  8. Neuroendocrine breast tumours: breast cancer or neuroendocrine cancer presenting in the breast?

    PubMed

    Adams, R W; Dyson, P; Barthelmes, L

    2014-04-01

    Neuroendocrine tumours (NET) of the breast are rare. Diagnosis depends on close scrutiny of core- or excisional-biopsy specimens for characteristic growth patterns (papillary, nesting or mixed), which should trigger immunohistochemical staining for neuroendocrine markers (in particular chromogranin and synaptophysin). The diagnosis is confirmed if a) >50% of the tissue specimen demonstrate neuroendocrine markers and b) in-situ ductal carcinoma is identified and/or imaging modalities exclude extra-mammary sites. Our literature search including the non-English literature identified 66 articles with data on 123 cases, including our own. Oestrogen receptors are not diagnostic for NET's of the breast as they are found in tumours of non-mammary origin, too. Half of reported cases of neuroendocrine tumours have axillary lymph node involvement. Breast-conserving surgery (wide local excision ± axillary clearance) is commonly performed for suitable tumours. Chemotherapy regimens utilised are commonly either platinum- (as for small-cell cancers) or anthracycline-based (as for primary breast cancers). Best management remains unknown. PMID:24342375

  9. Role of Staging in Patients with Small Intestinal Neuroendocrine Tumours.

    PubMed

    Clift, Ashley Kieran; Faiz, Omar; Al-Nahhas, Adil; Bockisch, Andreas; Liedke, Marc Olaf; Schloericke, Erik; Wasan, Harpreet; Martin, John; Ziprin, Paul; Moorthy, Krishna; Frilling, Andrea

    2016-01-01

    Small bowel neuroendocrine tumours are the commonest malignancy arising in the small intestine and have substantially increased in incidence in recent decades. Patients with small bowel neuroendocrine tumours commonly develop lymph node and/or distant metastases. Here, we examine the role of staging in 84 surgically treated patients with small bowel neuroendocrine tumours, comparing diagnostic information yielded from morphological, functional and endoscopic modalities. Furthermore, we correlate pre-operative staging with intra-operative findings in a sub-cohort of 20 patients. The vast majority of patients had been histologically confirmed to have low-grade (Ki-67 <2%) disease; however, lymph node and distant metastases were observed in 74 (88.1%) and 51 (60.7%) of patients at presentation, respectively. Liver metastases were evident in 48 (57.1%) patients, with solely peritoneal and bone metastases observed in 2 (2.4%) and 1 (1.2%) patients, respectively. Forty patients (47.6%) received multimodal treatment. In our sub-cohort analysis, pre-operative imaging understaged disease in 14/20 (70%) when compared with intra-operative findings. In patients with multifocal primary tumours and miliary liver metastases, no imaging modality was able to detect entire disease spread. Overall, presently available imaging modalities heavily underestimate disease stage, with meticulous intra-operative abdominal examination being superior to any imaging technology. Multimodal treatment has an important role in prolonging survival. PMID:26394880

  10. [Medical treatment of digestive neuroendocrine tumours].

    PubMed

    Panzuto, F; Nasoni, S; Delle Fave, G

    2001-09-01

    Surgery is the only therapy able to cure patients with digestive neuroendocrine tumor. However, due to the presence of diffuse metastases, radical surgery is often not feasible. In these cases, medical treatment plays a critical role, because of its ability to control symptoms in functioning tumors and to inhibit tumor growth. Different therapeutic approaches, such as chemotherapy, hepatic artery chemoembolization and targeted radio-nuclide therapy can be used alone or combined to the biologic treatment with somatostatin analogues and interferon. However, an accurate staging by imaging procedures plus a histological, immunohistochemical and biomolecular examination must be performed before planning an optimal medical treatment. PMID:11753237

  11. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin

    PubMed Central

    Mitry, E; Baudin, E; Ducreux, M; Sabourin, J-C; Rufié, P; Aparicio, T; Lasser, P; Elias, D; Duvillard, P; Schlumberger, M; Rougier, P

    1999-01-01

    The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3–4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3–4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed. © 1999 Cancer Research Campaign PMID:10604732

  12. Medical treatment for gastro-entero-pancreatic neuroendocrine tumours

    PubMed Central

    Berardi, Rossana; Morgese, Francesca; Torniai, Mariangela; Savini, Agnese; Partelli, Stefano; Rinaldi, Silvia; Caramanti, Miriam; Ferrini, Consuelo; Falconi, Massimo; Cascinu, Stefano

    2016-01-01

    Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -β), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing. PMID:27096034

  13. Lutetium-labelled peptides for therapy of neuroendocrine tumours.

    PubMed

    Kam, B L R; Teunissen, J J M; Krenning, E P; de Herder, W W; Khan, S; van Vliet, E I; Kwekkeboom, D J

    2012-02-01

    Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours. PMID:22388631

  14. Radionuclide therapy in neuroendocrine tumours: a systematic review.

    PubMed

    Gulenchyn, K Y; Yao, X; Asa, S L; Singh, S; Law, C

    2012-05-01

    The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be

  15. Diagnosis and treatment of a rare sinonasal neuroendocrine tumour: adding to the evidence.

    PubMed

    Gudlavalleti, Aashrai; Dean, Ryan; Liu, Yuxin; Dhamoon, Amit S

    2016-01-01

    Sinonasal neuroendocrine tumours (NETs) are rare, aggressive neoplasms with a high recurrence potential. There are no robust protocols for the management of these tumours. An 81-year-old man presented with an incidental sinonasal mass visualised on CT scan of head. Over the next few weeks he developed new onset, progressively worsening headache, right eye ptosis and restricted extraocular movements. Imaging confirmed a rapidly enlarging tumour involving the right nasal cavity and the orbit. Biopsy showed a large cell neuroendocrine carcinoma of the right ethmoidal sinus. The patient was treated with concurrent cisplatin chemotherapy and radiation. Repeat imaging showed decrease in tumour volume. The patient continues to do well and follows up regularly with our oncology service. Current protocols comprising chemotherapy after radiation are based on limited studies. A regimen involving concurrent chemoradiation also appears to aid in tumour volume reduction. Additional studies are required to formulate robust clinical protocols for management of sinonasal NETs. PMID:27624450

  16. Large cell neuroendocrine – Adenocarcinona mixed tumour of colon: Collision tumour with peculiar behaviour. What do we know about these tumours?

    PubMed Central

    Minaya-Bravo, Ana María; Garcia Mahillo, Julio Cesar; Mendoza Moreno, Fernando; Noguelares Fraguas, Fernando; Granell, Javier

    2015-01-01

    Introduction Mixed glandular-endocrine carcinomas are rare tumours of gastrointestinal tract (MANEC). They are more frequent in stomach and hardly one hundred cases have been described in colon. According to Lewis, they are classified into collision (side by side pattern), composite (intermingled) or amphicrine (neuroendocrine and glandular features inside a same cell). Collision tumours are related to biclonal theory: two simultaneous cancerogenic events. Conversely, multidirectional differentiation from a stem cell is accepted as origin of composite tumours. The aim of this paper is to analyse the behaviour of these tumours, with an especial concern about how these tumours metastasise, and the different theories about carcinogenesis. Presentation of case We report a rare case of collision adenocarcinoma-large cell neuroendocrine tumour of colon that after a three-year period of follow-up has presented a retroperitoneal recurrence that features adenocarcinoma and large cell neuroendocrine components. Discussion After an exhaustive review of the English literature, we found that only two cases of collision tumour of colon with metastases showing glandular and endocrine components have been described up to date, so we report the third case, and the first happening in transverse colon. Conclusion We conclude that not all collision tumours follow the biclonal theory and more studies are needed to clarify the origin of these neoplasms, and consequently, to reach an adequate treatment. PMID:26635955

  17. Malignant Glomus Tumour (Glomangiosarcoma) with Additional Neuroendocrine Differentiation in a Horse.

    PubMed

    Peters, M; Grafen, J; Kuhnen, C; Wohlsein, P

    2016-05-01

    A 13-year-old Icelandic crossbred horse was presented with headshaking and progressive impairment of chewing. A slowly growing mass was identified in the anterior maxilla. This was associated with lysis of the alveolar bone and the roots of the incisors and there were nodular proliferations affecting the nasal septum and conchae. There was no response to chemotherapy and so the horse was humanely destroyed. Based on morphological, immunohistochemical and ultrastructural findings the mass was classified as a malignant glomus tumour with multifocal vascular spaces and additional neuroendocrine differentiation. An oronasal glomus tumour with neuroendocrine differentiation has not been described previously in an animal. PMID:27102445

  18. [Efficacy of somatostatin analogues in the treatment of neuroendocrine tumours based on the results of recent clinical trials].

    PubMed

    Igaz, Péter

    2014-11-30

    Due to their inhibitory effects on hormone secretion, somatostatin analogues are of pivotal importance in the symptomatic treatment of hormone-secreting neuroendocrine tumours. Although several earlier clinical observations supported the view that these biological agents are capable of inhibiting the growth of neuroendocrine tumours, the PROMID study published in 2009 was the first to confirm the inhibitory effect of octreotide on tumour growth and demonstrated the prolongation of progression free survival. These findings have been confirmed and extended by the most recent CLARINET trial with lanreotide published in 2014. Somatostatin analogues are capable of inhibiting tumour growth and stabilizing disease irrespective of the hormonal activity of the tumour and, therefore, their applicability is expected to be extended to the treatment of hormonally inactive neuroendocrine tumours, as well. PMID:25417137

  19. Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

    PubMed Central

    Tsolakis, Apostolos V; Grimelius, Lars; Granerus, Göran; Stridsberg, Mats; Falkmer, Sture E; Janson, Eva T

    2015-01-01

    AIM: To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients. RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs. PMID:26715806

  20. [Pancreatic neuroendocrine tumours. What do we know of their history?].

    PubMed

    Navarro, Salvador

    2016-04-01

    Starting with Paul Langerhans, who first described pancreatic islets in 1869, this article reviews the various protagonists who, in the last century and a half, have contributed to the discovery of the main hormones originating in the pancreas, the analytical methods for their measurement, the imaging techniques for identifying tumoural location, and the various pancreatic neoplasms. PMID:26684677

  1. Contemporary methods of therapy and follow-up of neuroendocrine tumours of the gastrointestinal tract and the pancreas

    PubMed Central

    Fischbach, Jakub; Kamiński, Grzegorz; Ruchała, Marek

    2012-01-01

    The growing interest in neuroendocrine tumours is due to the dynamic growth of detection of this type of cancer. Neuroendocrine tumours (neuroendocrine neoplasms – NENs / neuroendocrine tumours – NETs) derive from glands, groups of endocrine cells and diffuse neuroendocrine system cells. Mainly they derive from the gastrointestinal tract (gastroenteropancreatic-neuroendocrine tumours – GEP-NETs). Currently the modified WHO classification from 2010 is widely used. An important element in the choice of treatment is histological maturity based on mitotic activity and on assessment of proliferation activity (Ki-67). The treatment of choice is surgery. In most cases, complete surgical removal is impossible because of the advanced staging at the time of diagnosis. In well-differentiated neoplasms where the expression of somatostatin receptors is expected, patients are qualified for somatostatin analogues therapy. Poorly differentiated lesions are qualified for chemotherapy. In the guidelines of ENETS (European Neuroendocrine Tumor Society) from 2007 the rules concerning monitoring depending on the WHO classification were specified. PMID:23788913

  2. Neuroendocrine tumours of the head and neck: anatomical, functional and molecular imaging and contemporary management

    PubMed Central

    Subedi, Navaraj; Prestwich, Robin; Chowdhury, Fahmid; Patel, Chirag

    2013-01-01

    Abstract Neuroendocrine tumours (NETs) of the head and neck are rare neoplasms and can be of epithelial or non-epithelial differentiation. Although the natural history of NETs is variable, it is crucial to establish an early diagnosis of these tumours as they can be potentially curable. Conventional anatomical imaging and functional imaging using radionuclide scintigraphy and positron emission tomography/computed tomography can be complementary for the diagnosis, staging and monitoring of treatment response. This article describes and illustrates the imaging features of head and neck NETs, discusses the potential future role of novel positron-emitting tracers that are emerging into clinical practice and reviews contemporary management of these tumours. Familiarity with the choice of imaging techniques and the variety of imaging patterns and treatment options should help guide radiologists in the management of this rare but important subgroup of head and neck neoplasms. PMID:24240099

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

    PubMed Central

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

    2015-01-01

    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. PMID:25754106

  4. Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings.

    PubMed

    Bagnasco, Giorgio; Properzi, Roberto; Porto, Roberto; Nardini, Vincenzo; Poli, Alessandro; Abramo, Francesca

    2003-04-01

    A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour. PMID:12662269

  5. Malignant Neuroendocrine Tumour (Carcinoid) of the Spleen in an African Pygmy Hedgehog (Atelerix albiventris).

    PubMed

    Lowden, L R; Davies, J L

    2016-07-01

    A malignant neuroendocrine tumour (carcinoid) of the spleen was diagnosed on post-mortem examination of a 3-year-old, male African pygmy hedgehog (Atelerix albiventris). The animal presented with a history of inappetence, weight loss, lethargy, a wide-based gait and a palpable abdominal mass. The gross pathological, histopathological, histochemical and immunohistochemical findings are described. Primary splenic carcinoids are reported rarely in the human medical literature and this is believed to be the first report in a non-human animal. PMID:27212029

  6. Multivisceral resection of pancreatic neuroendocrine tumours: a report of two cases

    PubMed Central

    2011-01-01

    Pancreatic neuroendocrine tumours (pNETs) are rare and surgical resection offers the only possibility of cure for localised disease. The role of surgery in the setting of locally advanced and metastatic disease is more controversial. Emerging data suggests that synchronous surgical resection of pancreas and liver may be associated with increased survival. We report two cases of synchronous, one stage multivisceral resections for pNET and associated reconstruction. We highlight the technical issues involved in such extensive resections and demonstrate that one stage multivisceral operations can be achieved safely. PMID:21859472

  7. Imaging secondary neuroendocrine tumours of the liver: comparison of I123 metaiodobenzylguanidine (MIBG) and In111-labelled octreotide (Octreoscan).

    PubMed

    Ramage, J K; Williams, R; Buxton-Thomas, M

    1996-07-01

    Functional imaging of neuroendocrine tumours with Octreoscan and I123-metaiodobenzylguanidine (MIBG) is important for assessment prior to various therapies and assessing response. The two imaging methods have not been directly compared in hepatic neuroendocrine tumours. Patients (n = 18) were studied with both imaging techniques. The sensitivity of Octreoscan was 94%, and that of MIBG 39%. No previously occult primary sites were detected. Concurrent octreotide therapy did not reduce the sensitivity of Octreoscan. Widespread bone metastases were seen in two post-liver-transplant patients using Octreoscan. Octreoscan is a sensitive means of detecting hepatic neuroendocrine tumours, and the more specific technique. MIBG has poor sensitivity, reducing its clinical utility. Therapy with I131-MIBG is likely to be applicable to relatively few patients. PMID:8759495

  8. Bowel parasitosis and neuroendocrine tumours of the appendix. A report from the Italian TREP project.

    PubMed

    Virgone, C; Cecchetto, G; Besutti, V; Ferrari, A; Buffa, P; Alaggio, R; Alessandrini, L; Dall'Igna, P

    2015-05-01

    Five children with a neuroendocrine tumour (NET) of the appendix associated with a parasitic bowel infection are described, and the possibility of inflammation-triggered carcinogenesis is discussed. Schistosoma haematobium is linked primarily to bladder cancer but it has been reported in association with several other histotypes, including NETs of the gastrointestinal tract. Conversely, Enterobius vermicularis has not yet been claimed to participate in the onset of pre-cancerous conditions or tumours. The rare occurrence of contemporary appendiceal NETs and parasitic infection, raises the intriguing hypothesis of an inflammation-related carcinogenesis, although a cause-effect relationship cannot be established. Larger international series of childhood appendiceal NETs, which also include countries with higher prevalence of parasitic bowel infections, are needed to further clarify this possible cause-effect relationship. PMID:25216117

  9. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study

    PubMed Central

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-01-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n=101) or placebo (n=103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n=41; placebo, n=47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  10. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    PubMed

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-03-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  11. Physiologically Based Pharmacokinetic (PBPK) Model for Biodistribution of Radiolabeled Peptides in Patients with Neuroendocrine Tumours

    PubMed Central

    Gospavic, Radovan; Knoll, Peter; Mirzaei, Siroos; Popov, Viktor

    2016-01-01

    Objective(s): The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK) models in patients with different neuroendocrine tumours (NET) who were treated with Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs) obtained by whole body scintigraphy (WBS) of the patients. Methods: The blood flow restricted (perfusion rate limited) type of the PBPK model for biodistribution of radiolabeled peptides (RLPs) in individual human organs is based on the multi-compartment approach, which takes into account the main physiological processes in the organism: absorption, distribution, metabolism and excretion (ADME). The approach calibrates the PBPK model for each patient in order to increase the accuracy of the dose estimation. Datasets obtained using WBS in four patients have been used to obtain the unknown model parameters. The scintigraphic data were acquired using a double head gamma camera in patients with different neuroendocrine tumours who were treated with Lu-177 DOTATATE. The activity administered to each patient was 7400 MBq. Results: Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved. Conclusion: The study indicates that the PBPK model can be used for more accurate calculation of biodistribution and absorbed doses in patients. This approach is the first attempt of utilizing scintigraphic data in PBPK models, which was obtained during Lu-177 peptide therapy of patients with NET. PMID:27408897

  12. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1.

    PubMed

    Yates, Christopher J; Newey, Paul J; Thakker, Rajesh V

    2015-11-01

    Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder, is characterised by the occurrence of pancreatic neuroendocrine tumours (P-NETs) in association with parathyroid and pituitary tumours. P-NETs, which include gastrinomas, insulinomas, and non-functioning tumours, occur in more than 80% of MEN1 patients and account for 50% of disease-specific deaths. However, there is no consensus about the optimal methods for detecting and treating P-NETs in MEN1 patients, and extrapolations from approaches used in patients with non-familial (sporadic) P-NETs require caution because of differences, such as the younger age of onset, multi-focality of P-NETs, and concomitant presence of other tumours in MEN1 patients. Thus, the early detection of P-NETs by circulating biomarkers and imaging modalities, and their appropriate treatments by surgical approaches and/or radionuclide therapy, chemotherapy, and biotherapy pose challenges and controversies. These challenges and controversies will be reviewed and possible approaches proposed. PMID:26165399

  13. Pathogenic PALB2 mutation in metastatic pancreatic adenocarcinoma and neuroendocrine tumour: A case report

    PubMed Central

    CHAN, DAVID; CLARKE, STEPHEN; GILL, ANTHONY J.; CHANTRILL, LORRAINE; SAMRA, JAS; LI, BOB T.; BARNES, TRISTAN; NAHAR, KAZI; PAVLAKIS, NICK

    2015-01-01

    Adenocarcinoma of the pancreas is an aggressive malignancy with poor prognosis. Pancreatic neuroendocrine tumours (PNET) comprise ~3% of primary pancreatic neoplasms and they are more heterogeneous in their histological character and outcome. This is the case report of a 73-year-old female patient with synchronously diagnosed pancreatic adenocarcinoma and PNET, which is likely associated with a pathogenic partner and localizer of breast cancer 2, early onset (PALB2) mutation. The potential pathogenic significance of PALB2 and its association with various malignancies were investigated and the potential role of PALB2 in conferring sensitivity to chemotherapeutic agents, such as mitomycin C and cisplatin, was discussed. This case report highlights the significance of ongoing research into the molecular pathogenesis of pancreatic cancer, which may help guide the selection of optimal treatments for this disease, as well as the need for ongoing study of PALB2 as a possible predictive marker of response to DNA-damaging agents. PMID:26171187

  14. Predictive factors of response to mTOR inhibitors in neuroendocrine tumours.

    PubMed

    Zatelli, Maria Chiara; Fanciulli, Giuseppe; Malandrino, Pasqualino; Ramundo, Valeria; Faggiano, Antongiulio; Colao, Annamaria

    2016-03-01

    Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs. PMID:26666705

  15. High intensity focused ultrasound ablation of pancreatic neuroendocrine tumours: report of two cases.

    PubMed

    Orgera, Gianluigi; Krokidis, Miltiadis; Monfardini, Lorenzo; Bonomo, Guido; Della Vigna, Paolo; Fazio, Nicola; Orsi, Franco

    2011-04-01

    We describe the use of ultrasound-guided high-intensity focused ultrasound (HIFU) for ablation of two pancreatic neuroendocrine tumours (NETs; insulinomas) in two inoperable young female patients. Both suffered from episodes of severe nightly hypoglycemia that was not efficiently controlled by medical treatment. After HIFU ablation, local disease control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 9-month follow-up. The lesions appeared to be decreased in volume, and there was decreased enhancing pattern in the multidetector computed tomography control (MDCT). HIFU is likely to be a valid alternative for symptoms control in patients with pancreatic NETs. However, currently the procedure should be reserved for inoperable patients for whom symptoms cannot be controlled by medical therapy. PMID:20521049

  16. High Intensity Focused Ultrasound Ablation of Pancreatic Neuroendocrine Tumours: Report of Two Cases

    SciTech Connect

    Orgera, Gianluigi; Krokidis, Miltiadis; Monfardini, Lorenzo; Bonomo, Guido; Della Vigna, Paolo; Fazio, Nicola; Orsi, Franco

    2011-04-15

    We describe the use of ultrasound-guided high-intensity focused ultrasound (HIFU) for ablation of two pancreatic neuroendocrine tumours (NETs; insulinomas) in two inoperable young female patients. Both suffered from episodes of severe nightly hypoglycemia that was not efficiently controlled by medical treatment. After HIFU ablation, local disease control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 9-month follow-up. The lesions appeared to be decreased in volume, and there was decreased enhancing pattern in the multidetector computed tomography control (MDCT). HIFU is likely to be a valid alternative for symptoms control in patients with pancreatic NETs. However, currently the procedure should be reserved for inoperable patients for whom symptoms cannot be controlled by medical therapy.

  17. Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours

    PubMed Central

    Kolesnikova, G. S.; Lapshina, A. M.; Voronkova, I. A.; Marova, E. I.; Arapova, S. D.; Goncharov, N. P.; Dedov, I. I.

    2013-01-01

    This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas. PMID:23509456

  18. MicroRNAs associated with small bowel neuroendocrine tumours and their metastases.

    PubMed

    Miller, Helen C; Frampton, Adam E; Malczewska, Anna; Ottaviani, Silvia; Stronach, Euan A; Flora, Rashpal; Kaemmerer, Daniel; Schwach, Gert; Pfragner, Roswitha; Faiz, Omar; Kos-Kudła, Beata; Hanna, George B; Stebbing, Justin; Castellano, Leandro; Frilling, Andrea

    2016-09-01

    Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted. PMID:27353039

  19. Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours

    NASA Astrophysics Data System (ADS)

    Gnanasegaran, Gopinath

    Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the

  20. Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours

    PubMed Central

    Yadegarfar, G; Friend, L; Jones, L; Plum, L M; Ardill, J; Taal, B; Larsson, G; Jeziorski, K; Kwekkeboom, D; Ramage, J K

    2013-01-01

    Background: Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours. Methods: This international multicentre validation study assesses the QLQ-GINET21 Quality of Life Questionnaire in 253 patients with gastrointestinal neuroendocrine tumours. All patients were requested to complete two quality of life questionnaires – the EORTC Core Quality of Life questionnaire (QLQ-C30) and the QLQ-GINET21 – at baseline, and at 3 and 6 months post-baseline; the psychometric properties of the questionnaire were then analysed. Results: Analysis of QLQ-GINET21 scales confirmed appropriate aggregation of the items, except for treatment-related symptoms, where weight gain showed low correlation with other questions in the scale; weight gain was therefore analysed as a single item. Internal consistency of scales using Cronbach's α coefficient was >0.7 for all parts of the QLQ-GINET21 at 6 months. Intraclass correlation was >0.85 for all scales. Discriminant validity was confirmed, with values <0.70 for all scales compared with each other. Scores changed in accordance with alterations in performance status and in response to expected clinical changes after therapies. Mean scores were similar for pancreatic and other tumours. Conclusion: The QLQ-GINET21 is a valid and responsive tool for assessing quality of life in the gut, pancreas and liver neuroendocrine tumours. PMID:23322194

  1. Learning experiences with sunitinib continuous daily dosing in patients with pancreatic neuroendocrine tumours

    PubMed Central

    Raymond, E.; Faivre, S.

    2014-01-01

    Molecular strategies to improve outcomes for patients with pancreatic neuroendocrine tumours (nets) have focused on targeting vascular endothelial growth factor, platelet-derived growth factor, and mtor (the mammalian target of rapamycin). This approach has led to the regulatory approval of two molecularly targeted agents for advanced pancreatic nets: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mtor inhibitor. Initial experience with sunitinib in advanced pancreatic net was gained from the phase iii registration trial, which used a continuous daily dosing (cdd) schedule instead of daily drug administration for 4 consecutive weeks every 6 weeks (schedule 4/2), the approved schedule for advanced renal cell carcinoma (rcc) and gastrointestinal stromal tumour (gist). Clinical experience gained with schedule 4/2 in rcc and gist shows that, using a therapy management approach, patients can start and be maintained on the recommended dose and schedule, thus optimizing treatment outcomes. Here, we discuss challenges that can potentially be faced by physicians who use sunitinib on the cdd schedule, and we use clinical data and real-life clinical experience to present therapy management approaches that support cdd in advanced pancreatic net. PMID:25489258

  2. Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.

    PubMed Central

    Wangberg, B.; Forssell-Aronsson, E.; Tisell, L. E.; Nilsson, O.; Fjalling, M.; Ahlman, H.

    1996-01-01

    After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors. Images Figure 1 Figure 2 Figure 3 PMID:8611378

  3. TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells.

    PubMed

    Skrzypski, Marek; Kołodziejski, Paweł A; Mergler, Stefan; Khajavi, Noushafarin; Nowak, Krzysztof W; Strowski, Mathias Z

    2016-08-01

    Highly Ca(2+) permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium, the activity of nuclear factor of activated T-cells (NFAT) and proliferation of BON-1 cells. TRPV6 expression was assessed by real-time PCR and Western blot. TRPV6 mRNA expression and protein production were down-regulated by siRNA. Changes in intracellular calcium levels were detected by fluorescence calcium imaging (fura-2/AM). NFAT activity was studied by NFAT reporter assay; cell proliferation by bromodeoxyuridine (BrdU), MTT and propidium iodine staining. TRPV6 mRNA and protein are present in BON-1 and QGP-1 NET-cells. Down-regulation of TRPV6 attenuates BON-1 cell proliferation. TRPV6 down-regulation is associated with decreased Ca(2+) response pattern and reduced NFAT activity. In conclusion, TRPV6 is expressed in pancreatic NETs and modulates cell proliferation via Ca(2+)-dependent mechanism, which is accompanied by NFAT activation. PMID:27450545

  4. TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells

    PubMed Central

    Skrzypski, Marek; Kołodziejski, Paweł A.; Mergler, Stefan; Khajavi, Noushafarin; Nowak, Krzysztof W.; Strowski, Mathias Z.

    2016-01-01

    Highly Ca2+ permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium, the activity of nuclear factor of activated T-cells (NFAT) and proliferation of BON-1 cells. TRPV6 expression was assessed by real-time PCR and Western blot. TRPV6 mRNA expression and protein production were down-regulated by siRNA. Changes in intracellular calcium levels were detected by fluorescence calcium imaging (fura-2/AM). NFAT activity was studied by NFAT reporter assay; cell proliferation by bromodeoxyuridine (BrdU), MTT and propidium iodine staining. TRPV6 mRNA and protein are present in BON-1 and QGP-1 NET-cells. Down-regulation of TRPV6 attenuates BON-1 cell proliferation. TRPV6 down-regulation is associated with decreased Ca2+ response pattern and reduced NFAT activity. In conclusion, TRPV6 is expressed in pancreatic NETs and modulates cell proliferation via Ca2+-dependent mechanism, which is accompanied by NFAT activation. PMID:27450545

  5. Malignant neuroendocrine tumour of the gallbladder with elevated carcinoembryonic antigen: case report and literature review

    PubMed Central

    Furrukh, Muhammad; Qureshi, Asim; Saparamadu, Anna; Kumar, Shiyam

    2013-01-01

    A 58-year-old woman presented to a tertiary care centre with signs and symptoms of acute cholecystitis, cholelithiasis and diagnoses of a high-grade neuroendocrine tumour of the gallbladder primarily with peritoneal and liver metastases. She had a liver abscess secondary to Salmonella and Enterococcus fecalis that was drained and treated with appropriate antibiotics. Interestingly, the serum chromogranin A levels were within normal limits, but carcinoembryonic antigen was elevated, which helped evaluate responses and pick progression. She was treated with 10 cycles of palliative chemotherapy when malignancy associated complications started to recur, that is, cholangitis, worsening pain, cachexia, intestinal obstruction, etc leading to chemotherapy delays. Her disease progressed during these times with rapid deterioration of performance status. She died of septic complications postlaparotomy for intestinal obstruction. Her progression-free survival remained for 8 months with subjective and objective improvements, and her overall survival remained at 13 months. We describe the course of her illness and give a brief review of the literature. PMID:23661652

  6. Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review.

    PubMed

    Chau, I; Casciano, R; Willet, J; Wang, X; Yao, J C

    2013-11-01

    Neuroendocrine tumours (NET) are often diagnosed at an advanced stage when the prognosis is poor for patients, who often experience diminished quality of life (QoL). As new treatments for NET become available, it is important to characterise the associated outcomes, costs and QoL. A comprehensive search was performed to systematically review available data in advanced NET regarding cost of illness/resource utilisation, economic studies/health technology assessment and QoL. Four rounds of sequential review narrowed the search results to 22 relevant studies. Most focused on surgical procedures and diagnostic tools and contained limited information on the costs and consequences of medical therapies. Multiple tools are used to assess health-related QoL in NET, but few analyses have been conducted to assess the comparative impact of available treatment alternatives on QoL. Limitations include English language and the focus on advanced NET; ongoing terminology and classification changes prevented pooled statistical analyses. This systematic review suggests a lack of comparative economic and outcomes data associated with NET treatments. Further research on disease costs, resource utilisation and QoL for patients with advanced NET is warranted. PMID:23895457

  7. Primary neuroendocrine tumour of the right ventricle presenting with heart failure and cyanosis.

    PubMed

    Naqvi, Syed Yaseen; Henry, David; Furukawa, Satoshi; Haber, Howard

    2016-01-01

    A 68-year-old woman presented to the emergency department owing to exertional dyspnoea and bilateral leg oedema for 3 weeks. Her vital signs included the following: heart rate of 95 bpm, respiratory rate of 24 breaths/min, oxygen saturation of 73% on room air and a blood pressure of 184/108 mm Hg. Physical examination revealed tachypnoea with clear lungs to auscultation, elevated jugular veins, cyanosis and bilateral pitting oedema. A chest X-ray demonstrated cardiomegaly without obvious pulmonary oedema. A CT of the chest was negative for pulmonary embolus; however, the scan did reveal a large right ventricular (RV) mass. An echocardiogram with bubble study confirmed a patent foramen ovale with significant right-to-left shunting and a large RV mass that significantly obstructed the pulmonary outflow tract. A cardiac biopsy revealed a low-grade neuroendocrine tumour. The patient underwent successful debridement and adjuvant chemotherapy. She improved greatly and was asymptomatic at a 9-month follow-up visit. PMID:26969366

  8. Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review

    PubMed Central

    Chau, I; Casciano, R; Willet, J; Wang, X; Yao, JC

    2013-01-01

    Neuroendocrine tumours (NET) are often diagnosed at an advanced stage when the prognosis is poor for patients, who often experience diminished quality of life (QoL). As new treatments for NET become available, it is important to characterise the associated outcomes, costs and QoL. A comprehensive search was performed to systematically review available data in advanced NET regarding cost of illness/resource utilisation, economic studies/health technology assessment and QoL. Four rounds of sequential review narrowed the search results to 22 relevant studies. Most focused on surgical procedures and diagnostic tools and contained limited information on the costs and consequences of medical therapies. Multiple tools are used to assess health-related QoL in NET, but few analyses have been conducted to assess the comparative impact of available treatment alternatives on QoL. Limitations include English language and the focus on advanced NET; ongoing terminology and classification changes prevented pooled statistical analyses. This systematic review suggests a lack of comparative economic and outcomes data associated with NET treatments. Further research on disease costs, resource utilisation and QoL for patients with advanced NET is warranted. PMID:23895457

  9. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging.

    PubMed

    Shi, W; Johnston, C F; Buchanan, K D; Ferguson, W R; Laird, J D; Crothers, J G; McIlrath, E M

    1998-04-01

    A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1-octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]-octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES. PMID:9666953

  10. Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours.

    PubMed

    Vitali, Eleonora; Cambiaghi, Valeria; Zerbi, Alessandro; Carnaghi, Carlo; Colombo, Piergiuseppe; Peverelli, Erika; Spada, Anna; Mantovani, Giovanna; Lania, Andrea G

    2016-03-01

    Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (-43 ± 21%, P < 0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (-46 ± 18%, P < 0.05 vs untreated cells), P-ERK1/2 levels (-42 ± 14%; P < 0.05 vs untreated cells), cAMP accumulation (-24 ± 3%, P < 0.05 vs untreated cells), VEGF expression (-31 ± 5%, P < 0.01 vs untreated cells) and in vitro release (-40 ± 24%, P < 0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (+86 ± 45%, P < 0.05 vs untreated cells) and inhibited cell migration (-24 ± 2%, P < 0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients. PMID:26733502

  11. A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

    PubMed Central

    Farah, G; Stokes, V J; Wang, L M; Grossman, A B

    2016-01-01

    Summary We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Learning points Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndrome There is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs) The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohort An exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populations The relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases PMID:27252866

  12. Current Status of Interventional Radiology in the Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours (GEP-NETs)

    SciTech Connect

    Orgera, Gianluigi; Krokidis, Miltiadis; Cappucci, Matteo; Gourtsoyianni, Sofia; Tipaldi, Marcello Andrea; Hatzidakis, Adam; Rebonato, Alberto; Rossi, Michele

    2015-02-15

    Within the group of Gastro-Entero-Pancreatic Neuroendocrine tumours (GEP-NETs), several heterogeneous malignancies are included with a variety of clinical manifestations and imaging characteristics. Often these cases are inoperable and minimal invasive treatment offered by image-guided procedures appears to be the only option. Interventional radiology offers a valid solution in the management of primary and metastatic GEP-NETs. The purpose of this review article is to describe the current status of the role of Interventional Radiology in the management of GEP-NETs.

  13. Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours

    PubMed Central

    Mairinger, Fabian Dominik; Walter, Robert Fred Henry; Theegarten, Dirk; Hager, Thomas; Vollbrecht, Claudia; Christoph, Daniel Christian; Worm, Karl; Ting, Saskia; Werner, Robert; Stamatis, Georgios; Mairinger, Thomas; Baba, Hideo; Zarogoulidis, Konstantinos; Huang, Haidong; Li, Qiang; Tsakiridis, Kosmas; Zarogoulidis, Paul; Schmid, Kurt Werner; Wohlschlaeger, Jeremias

    2014-01-01

    Background: Proteasomal subunit PSMB4 was suggested to be a survival gene in an animal model of hepatocellular carcinoma and in glioblastoma cell lines. In pulmonary adenocarcinoma, a high expression of these genes was found to be associated with poor differentiation and survival. This study investigates the gene expression levels of 26S proteasome subunits in human pulmonary neuroendocrine tumours including typical (TC) and atypical (AC) carcinoid tumours as well as small cell (SCLC) and large cell (LCNEC) neuroendocrine carcinomas. Material and methods: Gene expression levels of proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 neuroendocrine pulmonary tumours (each 20 TC, AC, LCNLC and SCLC) and compared to controls. mRNA levels were determined by using TaqMan assays. Immunohistochemistry on tissue microarrays (TMA) was performed to determine the expression of ki67, cleaved caspase 3 and PSMB4. Results: All proteasomal subunit gene expressions were significantly upregulated in TC, AC, SCLC and LCNEC compared to controls. PSMB4 mRNA is differently expressed between all neuroendocrine tumour subtypes demonstrating the highest expression and greatest range in LCNEC (p=0.043), and is significantly associated with proliferative activity (p=0.039). Conclusion: In line with other 26S proteasomal subunits PSMB4 is significantly increased, but differently expressed between pulmonary neuroendocrine tumours and is associated with the proliferative activity. Unlike in pulmonary adenocarcinomas, no association with biological behaviour was observed, suggesting that increased proteasomal subunit gene expression is a common and probably early event in the tumorigenesis of pulmonary neuroendocrine tumours regardless of their differentiation. PMID:25157275

  14. Well-Differentiated Grade 2, Type 3 Gastrointestinal Neuroendocrine Tumour with Bilateral Metastatic Ovarian Involvement: Report of an Unusual Case

    PubMed Central

    Manneh, Ray; Castellano, Daniel; Caso, Oscar; Loinaz, Carmelo; Jiménez, Jesús; Estenoz, Juana; Calatayud, Maria; Sepúlveda, Juan M.; García-Carbonero, Rocio

    2016-01-01

    Treatment of metastatic gastric neuroendocrine tumours (NETs) is challenging. In oligometastatic cases, surgical resection is recommended whenever possible. Somatostatin analogues have been used to decrease gastrin levels, and available evidence suggests that these drugs can also reduce recurrences. Here we present a highly unusual case involving a patient with a well-differentiated grade 2, type 3 gastric NET with exclusive metastatic bilateral ovarian involvement. To our knowledge, this is the first such case reported in the literature, as the cause of ovarian involvement is usually due to local invasion rather than metastasis. We believe this case is of interest not only due to the unusual presentation, but also because it makes us consider adjuvant treatment with somatostatin analogues in patients with low-grade tumours and a positive postoperative octreoscan. PMID:27239181

  15. Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour

    PubMed Central

    Teng, Jessie; Dowling, Anthony; Hofman, Michael S; MacIsaac, Richard J; Sachithanandan, Nirupa

    2015-01-01

    Summary This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs. Learning points Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.PRRT is emerging as a therapeutic option with high efficacy and

  16. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study

    PubMed Central

    Phan, Alexandria T; Halperin, Daniel M; Chan, Jennifer A; Fogelman, David R; Hess, Kenneth R; Malinowski, Paige; Regan, Eileen; Ng, Chaan S; Yao, James C; Kulke, Matthew H

    2015-01-01

    Summary Background Treatment options for advanced, well-differentiated neuroendocrine tumours (NETs) remain scarce. Pazopanib is an orally bioavailable, small molecule, multitargeted kinase inhibitor that inhibits VEGF receptors 1, 2, and 3. We did a study of the efficacy of pazopanib with depot octreotide in patients with advanced NETs. Methods We did a parallel cohort study of patients with metastatic or locally advanced grade 1–2 carcinoid tumours or pancreatic NETs, by use of a single-group, two-stage design. Patients received pazopanib 800 mg orally once per day and octreotide at their preprotocol dosage. The primary endpoint was the proportion of patients achieving an objective response, as assessed by investigators, by intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00454363, and was completed in March, 2014. Findings Between April 12, 2007, and July 2, 2009, we enrolled 52 patients, including 32 individuals with pancreatic NETs and 20 individuals with carcinoid tumours. Seven (21.9%, 95% CI 11.0–38.8) of 32 patients with pancreatic NETs achieved an objective response. We detected no responses in the first stage of the cohort with carcinoid tumours, and we terminated accrual at 20 patients. Toxic effects included one patient with grade 4 hypertriglyceridaemia and one with grade 4 thrombosis, with the most common grade three events being aminotransferase increases and neutropenia, each of which happened in 3 patients. In all 52 patients, the most frequently observed toxic effects were fatigue (39 [75%]), nausea (33 [63%]), diarrhoea (33 [63%]), and hypertension (28 [54%]). Interpretation Treatment with pazopanib is associated with tumour response for patients with pancreatic NETs, but not for carcinoid tumours; a randomised controlled phase 3 study to assess pazopanib in advanced pancreatic NETs is warranted. Funding US National Cancer Institute of the National Institutes of Health. PMID:25956795

  17. Screening for malnutrition in patients with gastro-entero-pancreatic neuroendocrine tumours: a cross-sectional study

    PubMed Central

    Qureshi, Sheharyar A; Burch, Nicola; Druce, Maralyn; Hattersley, John G; Khan, Saboor; Gopalakrishnan, Kishore; Darby, Catherine; Wong, John L H; Davies, Louise; Fletcher, Simon; Shatwell, William; Sothi, Sharmila; Randeva, Harpal S; Dimitriadis, Georgios K; Weickert, Martin O

    2016-01-01

    Objectives To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET). Design Cross-sectional study. Setting University Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence. Participants Patients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities. Main outcome measure To identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment. Results MUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients. Conclusions Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues. PMID:27147385

  18. Somatostatin Analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life

    PubMed Central

    Faggiano, Antongiulio; Carratù, Anna Chiara; Guadagno, Elia; Tafuto, Salvatore; Tatangelo, Fabiana; Riccardi, Ferdinando; Mocerino, Carmela; Palmieri, Giovannella; Damiano, Vincenzo; Siciliano, Roberta; Leo, Silvana; Mauro, Annamaria; Tozzi, Lucia Franca; Battista, Claudia; De Rosa, Gaetano; Colao, Annamaria

    2016-01-01

    Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy. PMID:26701729

  19. Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.

    PubMed

    Faggiano, Antongiulio; Carratù, Anna Chiara; Guadagno, Elia; Tafuto, Salvatore; Tatangelo, Fabiana; Riccardi, Ferdinando; Mocerino, Carmela; Palmieri, Giovannella; Damiano, Vincenzo; Siciliano, Roberta; Leo, Silvana; Mauro, Annamaria; Tozzi, Lucia Franca; Battista, Claudia; De Rosa, Gaetano; Colao, Annamaria

    2016-02-01

    Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy. PMID:26701729

  20. Selective Internal Radiation Therapy for Gastrointestinal Neuroendocrine Tumour Liver Metastases: A New and Effective Modality for Treatment

    PubMed Central

    Rajekar, Harshal; Bogammana, Kashan; Stubbs, Richard S.

    2011-01-01

    Background. Nonresectable neuroendocrine tumour (NET) liver metastases respond poorly to most widely available and used therapies. Selective Internal Radiation Therapy (SIRT) is becoming recognized as a new modality for selectively treating non-resectable liver tumours. This paper presents an experience of 14 patients with non-resectable NET liver metastases treated with SIRT. Methods. Between September 1997 and October 2009 14 patients with extensive NET liver metastases were treated with 2.0 to 3.0 GBq of 90Yttrium microspheres. Repeat SIRT was undertaken in three patients after 16, 27, and 48 months, respectively. Responses were assessed clinically, biochemically, and with serial CT scans. Survival was measured from initial SIRT. Results. Some response was seen in all 14 patients. Carcinoid syndrome improved or resolved in 10/10 instances. 24-hour urinary 5-HIAA or serum chromogranin A levels fell dramatically in 5/7 patients following SIRT. Serial CT scans revealed partial response or stable disease in all 14 patients. Repeat treatment in three patients experiencing progression was associated with a further response. Median survival after SIRT is 25 months with 6 patients being alive (and 3 patients still asymptomatic), at 19, 22, 23, 23, 58, and 60 months. Conclusions. SIRT is an effective and well-tolerated treatment for non-resectable NET liver metastases capable of both alleviating the carcinoid syndrome and achieving significant tumour regression. Repeat treatment is an option and liver resection after downstaging may also become possible. PMID:22164335

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

    PubMed Central

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

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management. PMID:27610194

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

    PubMed

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

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management. PMID:27610194

  3. Dysregulation of autocrine TGF-beta isoform production and ligand responses in human tumour-derived and Ha-ras-transfected keratinocytes and fibroblasts.

    PubMed Central

    Fahey, M. S.; Paterson, I. C.; Stone, A.; Collier, A. J.; Heung, Y. L.; Davies, M.; Patel, V.; Parkinson, E. K.; Prime, S. S.

    1996-01-01

    This study examined the autocrine production of TGF-beta 1, -beta 2 and -beta 3 in culture supernatants from tumour-derived (H series, n = 7; BICR series, n = 5), Ha-ras-transfected (n = 4) and normal (n = 2) human keratinocytes using a sandwich enzyme-linked immunosorbent assay (ELISA). Detection limits were 39.0 pg ml-1 for TGF-beta 1, 78.0 pg ml-1 for TGF-beta 2 and 1.9 ng ml-1 for TGF-beta 3. Tumour-derived oral keratinocytes predominantly produced less TGF-beta 1 than normal oral epithelial cells; the expression of endogenous TGF-beta 2 was variable. In keratinocytes containing mutant Ha-ras, TGF-beta 1 production was enhanced and TGF-beta 2 was undetectable. TGF-beta 3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) but the protein was not detected in conditioned media, most probably because of the low detection limits of the ELISA for this isoform. Neutralisation experiments indicated that the latent TGF-beta peptide was secreted in keratinocyte conditioned medium. Seven tumour-derived keratinocyte cell lines (H series) and fibroblasts separated from normal (n = 1) and tumour-derived (n = 2) keratinocyte cultures were examined for their response to exogenous TGF-beta 1, -beta 2 and -beta 3. Six of seven tumour-derived keratinocyte cell lines were inhibited by TGF-beta 1 and TGF-beta 2 (-beta 1 > -beta 2); one cell line was refractory to both TGF-beta 1 and TGF-beta 2. Keratinocytes were inhibited (4 of 7), stimulated (1 of 7) or failed to respond (2 of 7) to TGF-beta 3, TGF-beta 1, -beta 2 and -beta 3 stimulated both normal and tumour-associated fibroblasts, but the tumour-associated fibroblasts showed less response to the ligands than their normal counterparts following prolonged treatment with each isoform. The results demonstrate variable autocrine production of TGF-beta isoforms by malignant keratinocytes, with loss of TGF-beta 1 generally associated with the tumour-derived phenotype and modification of endogenous isoform

  4. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

    PubMed Central

    2013-01-01

    Background Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. Methods This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Results Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. Trial registration ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18. PMID:24053191

  5. Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings

    PubMed Central

    Tartour, E; Mehtali, M; Sastre-Garau, X; Joyeux, I; Mathiot, C; Pleau, J M; Squiban, P; Rochlitz, C; Courtney, M; Jantscheff, P; Herrmann, R; Pouillart, P; Fridman, W H; Dorval, T

    2000-01-01

    Various studies have emphasized an immunodepression state observed at the tumour site. To reverse this defect and based upon animal studies, we initiated a phase I clinical trial of gene therapy in which various doses of xenogeneic monkey fibroblasts (Vero cells) genetically engineered to produce human IL-2 were administered intratumorally in 8 patients with metastatic solid tumours. No severe adverse effect was observed in the 8 patients analysed during this clinical trial even in the highest dose (5 ¥ 107 cells) group. This absence of toxicity seems to be associated with rapid elimination of Vero-IL-2 cells from the organism. Indeed, exogenous IL-2 mRNA could no longer be detected in the peripheral whole blood 48 hours after Vero-IL-2 cell administration. In addition, we did not find any expression of exogenous IL-2 mRNA in post-therapeutic lesions removed 29 days after the start of therapy. A major finding of this trial concerns the two histological responses of two treated subcutaneous nodules not associated with an apparent clinical response. The relationship between local treatment and tumour regression was supported by replacement of tumour cells by inflammatory cells in regressing lesions and marked induction of T and natural killer cell derived cytokines (IL-2, IL-4, IFNg …) in post-therapeutic lesions analysed 28 days after the start of Vero-IL-2 administration. Gene therapy using xenogeneic cells as vehicle may therefore present certain advantages over other vectors, such as its complete absence of toxicity. Furthermore, the in vivo biological effect of immunostimulatory genes, i.e IL-2-, may be potentiated by the xenogeneic rejection reaction. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076653

  6. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference

    PubMed Central

    Kennedy, Andrew; Bester, Lourens; Salem, Riad; Sharma, Ricky A; Parks, Rowan W; Ruszniewski, Philippe

    2015-01-01

    Objectives Liver metastasis from a neuroendocrine tumour (NET) represents a significant clinical entity. A multidisciplinary group of experts was convened to develop state-of-the-art recommendations for its management. Methods Peer-reviewed published reports on intra-arterial therapies for NET hepatic metastases were reviewed and the findings presented to a jury of peers. The therapies reviewed included transarterial embolization (TAE), transarterial chemoembolization (TACE) and radioembolization (RE). Two systems were used to evaluate the level of evidence in each publication: (i) the US National Cancer Institute (NCI) system, and (ii) the GRADE system. Results Eighteen publications were reviewed. These comprised 11 reports on TAE or TACE and seven on RE. Four questions posed to the panel were answered and recommendations offered. Conclusions Studies of moderate quality support the use of TAE, TACE and RE in hepatic metastases of NETs. The quality and strength of the reports available do not allow any modality to be determined as superior in terms of imaging response, symptomatic response or impact on survival. Radioembolization may have advantages over TAE and TACE because it causes fewer side-effects and requires fewer treatments. Based on current European Neuroendocrine Tumor Society (ENETS) Consensus Guidelines, RE can be substituted for TAE or TACE in patients with either liver-only disease or those with limited extrahepatic metastases. PMID:25186181

  7. Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract and pancreas.

    PubMed

    de Herder, W W; Krenning, E P; Van Eijck, C H J; Lamberts, S W J

    2004-03-01

    Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise. PMID:15027883

  8. Diagnostic Utility of PET CT in Thymic Tumours with Emphasis on 68Ga-DOTATATE PET CT in Thymic Neuroendocrine Tumour - Experience at a Tertiary Level Hospital in India

    PubMed Central

    Shanthly, Nylla; Oommen, Regi

    2014-01-01

    Introduction:18 Fluorine-fluoro-2-deoxyglucose positron emis–sion tomography/computed tomography (18F- FDG-PET/CT) is of importance in assessing high-risk thymoma and thymic carcinomas. Detection of advanced thymoma versus thymic carcinoma by routine cross sectional anatomical imaging such as computed tomography (CT), magnetic resonance imaging (MRI) often poses a diagnostic dilemma. In this case series we observed the utility of FDG uptake to predict advanced thymoma and distinguish thymoma from thymic cancer. Materials and Methods: We reviewed 18F- FDG-PET/CT scans of 12 patients (8 males, 4 females); age 24-60yrs with thymic epithelial malignancy from January 2011 to May 2013. FDG activity in lesions was quantified using maximum standardised uptake value (SUVmax) and correlated with Masaoka staging and WHO classification. All patients fasted 4 hr prior to 18F-FDG PET/CT. Images from vertex to mid-thigh were acquired 60min post injection of 3.7 -4.7 MBq/kg (Mega Becquerel)/kilogram of18F-FDG and SUV max of each tumour was measured. One patient underwent DOTATATE scan, received 138MBq of 68Gallium (68Ga)-DOTATATE injection IV and imaging was done after 60 min. Results: Higher FDG uptake of SUVmax 7.35 was seen in type B3 thymoma. FDG uptake was higher in thymic carcinoma (20.45 in primary and 17.46 in the node) or neuroendocrine differentiation (NED) than in patients with thymomas (ranged 7.35 - 3.02). No significant association was observed between higher focal FDG uptake and advanced-stage disease in thymoma. In NED 68Ga - DOTATATE imaging identified more lesions than in FDG. Conclusion: PET CT is a valuable diagnostic tool in evaluation of thymic tumours, to assess in initial workup, for treatment response and for prognostication. 68Ga-DOTATATE PET/CT is beneficial in assessing neuroendocrine thymic tumours. Focal FDG uptake cannot predict advanced thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the more aggressive thymoma B3. PMID

  9. Peptide receptor radionuclide therapy with 90Y-DOTATATE/90Y-DOTATOC in patients with progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity

    PubMed Central

    Vinjamuri, S; Gilbert, T M; Banks, M; McKane, G; Maltby, P; Poston, G; Weissman, H; Palmer, D H; Vora, J; Pritchard, D M; Cuthbertson, D J

    2013-01-01

    Background: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to 90Y-DOTATOC/90Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures. Methods: A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed. Results: Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare. Conclusion: In patients with progressive metastatic NETs receiving 90Y-DOTATOC/90Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit. PMID:23492685

  10. Modifications in the head group and in the spacer of cholesterol-based cationic lipids promote transfection in melanoma B16-F10 cells and tumours.

    PubMed

    Reynier, P; Briane, D; Coudert, R; Fadda, G; Bouchemal, N; Bissieres, P; Taillandier, E; Cao, A

    2004-01-01

    A series of four cationic lipids derived from cholesterol was synthesised and their efficiencies to vectorise nucleic acids were compared. The investigation concerns the effects of systematic chemical modifications in the polar head and in the spacer. The cationic lipid molecules used are in the same family of 3beta[N-(N',N',N'-trimethylaminoethane)-carbamoyl] cholesterol iodide (TMAEC-Chol), presenting a spacer of two or three carbons and a quaternary ammonium polar head ramified with methyl or ethyl groups. These lipids formed stable liposomes sizing from 100 to 200 nm when prepared with the colipid dioleoyl phosphatidylethanolamine (DOPE). The goal of this work was to investigate the effect of the chemical structure of these cationic lipids on lipofection. Their ability to form complexes with DNA, their cytotoxicity and their transfection efficiency in vitro and in vivo were studied. Results were compared with those obtained from the well known cholesterol-based cationic lipid DC-Chol. In a melanoma cell line (B16-F10), results showed that either the polar head or the spacer affected the cytotoxicity. Cationic lipids with three ethyl groups in the head are more toxic than those with three methyl groups while cationic lipids with three carbons in the spacer are less toxic than those with two carbons in the spacer. The best transfection level was obtained in vitro and in vivo with cationic lipids having 3C in the spacer. Data indicated that among these lipids, in vivo gene transfer is advantaged by the methylated polar head while in vitro the best level was obtained with the ethylated one. Finally, it was observed that the chemical structure influences the transfection in the presence of serum while the complex charge and the DOPE ratios in liposomes preferentially affect the interaction with erythrocytes. Argumentations are proposed to explain the discrepancies between in vitro and in vivo transfection results concerning the optimal charge ratio and the chemical

  11. [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

    PubMed Central

    Baum, Richard P.; Kluge, Andreas W.; Kulkarni, Harshad; Schorr-Neufing, Ulrike; Niepsch, Karin; Bitterlich, Norman; van Echteld, Cees J.A.

    2016-01-01

    Purpose: To characterise efficacy and safety of 177Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with 177Lu-DOTATOC were analysed retrospectively. Subjects were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion: 177Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with

  12. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome.

    PubMed

    Rossi, Giulio; Cavazza, Alberto; Spagnolo, Paolo; Sverzellati, Nicola; Longo, Lucia; Jukna, Agita; Montanari, Gloria; Carbonelli, Cristiano; Vincenzi, Giada; Bogina, Giuseppe; Franco, Renato; Tiseo, Marcello; Cottin, Vincent; Colby, Thomas V

    2016-06-01

    The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome. PMID:27076588

  13. Ga-68 DOTANOC PET/CT imaging in detection of primary site in patients with metastatic neuroendocrine tumours of unknown origin and its impact on clinical decision making: experience from a tertiary care centre in India

    PubMed Central

    Pankaj, Promila; Verma, Ritu; Jain, Anjali; Belho, Ethel S.; Mahajan, Harsh

    2016-01-01

    Background Neuroendocrine tumours (NETs) are rare, heterogeneous group of tumours which usually originate from small, occult primary sites and are characterized by over-expression of somatostatin receptors (SSTRs). Positron emission tomography/computed tomography (PET/CT) using Ga-68-labeled-somatostatin-analogues have shown superiority over other modalities for imaging of NETs. The objective of the study was to retrospectively evaluate the efficacy of Ga-68 DOTANOC PET/CT imaging in detecting the primary site in patients with metastatic NETs of unknown origin and its impact on clinical decision making in such patients. Methods Between December 2011 and September 2014, a total of 263 patients underwent Ga-68 DOTANOC PET/CT study in our department for various indications. Out of them, 68 patients (45 males, 23 females; mean age, 54.9±10.7 years; range, 31–78 years) with histopathologically proven metastatic NETs and unknown primary site (CUP-NET) on conventional imaging, who underwent Ga-68 DOTANOC PET/CT scan as part of their clinical work-up were included for analyses. Histopathology (wherever available) and/or follow-up imaging were taken as reference standard. Quantitative estimation of SSTR expression in the form of maximal standardized uptake value (SUVmax) of detected primary and metastatic sites was calculated. Follow-up data of individual patients was collected through careful survey of hospital medical records and telephonic interviews. Results Maximum patients presented to our department with hepatic metastasis (50 out of 68 patients) and grade I NETs (>50%). Ga-68 DOTANOC PET/CT scan identified primary sites in 40 out of these 68 patients i.e., in approximately 59% patients. Identified primary sites were: small intestine [19], rectum [8], pancreas [7], stomach [4], lung [1] and one each in rare sites in kidney and prostate. In one patient, 2 primary sites were identified (one each in stomach and duodenum). Mean SUVmax of the detected primary sites was

  14. Neuroendocrine differentiation in cervical carcinoma.

    PubMed Central

    Savargaonkar, P R; Hale, R J; Mutton, A; Manning, V; Buckley, C H

    1996-01-01

    AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour. Images PMID:8655680

  15. Clinical features of gastroenteropancreatic tumours

    PubMed Central

    Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  16. Acute Disseminated Intravascular Coagulation in Neuroendocrine Carcinoma

    PubMed Central

    Teh, Ru-Wen; Tsoi, Daphne T.

    2012-01-01

    Malignancy is a common cause of disseminated intravascular coagulation and usually presents as a chronic disorder in solid organ tumours. We present a rare case of recurrent acute disseminated intravascular coagulation in neuroendocrine carcinoma after manipulation, firstly, by core biopsy and, later, by cytotoxic therapy causing a release of procoagulants and cytokines from lysed tumour cells. This is reminiscent of tumour lysis syndrome where massive quantities of intracellular electrolytes and nucleic acid are released, causing acute metabolic imbalance and renal failure. This case highlights the potential complication of acute disseminated intravascular coagulation after trauma to malignant cells. PMID:23139666

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

    PubMed Central

    McGinness, Sam; Coleman, Hedley; Varikatt, Winny; da Cruz, Melville

    2016-01-01

    Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours. PMID:27429819

  18. Neuroendocrine Tumor: Statistics

    MedlinePlus

    ... Tumor > Neuroendocrine Tumor - Statistics Request Permissions Neuroendocrine Tumor - Statistics Approved by the Cancer.Net Editorial Board , 04/ ... the body. It is important to remember that statistics on how many people survive this type of ...

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

    PubMed

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

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. PMID:25670668

  20. Small Cell Neuroendocrine Carcinoma of the Cervix: A Rare Entity

    PubMed Central

    V, Pavithra; Shalini, C.N. Sai; Priya, Shanmuga; Rani, Usha; Rajendiran, S; Joseph, Leena Dennis

    2014-01-01

    Small cell carcinoma of the cervix is a rare and a very aggressive tumour. Once being considered to be a rare type of squamous cell carcinoma, evidence has proven that most of the tumours express one or more markers of neuroendocrine differentiation. The behaviour of this rare malignancy is different from that of squamous cell carcinomas, with a high propensity for nodal and distant metastases. Hence, there is a need to highlight this histopathological entity. PMID:24701511

  1. [Tumours and liver transplants].

    PubMed

    Mejzlík, Vladimír; Husová, Libuše; Kuman, Milan; Štěpánková, Soňa; Ondrášek, Jiří; Němec, Petr

    2015-01-01

    Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID:26375706

  2. Multimodal management of neuroendocrine liver metastases

    PubMed Central

    Frilling, Andrea; Sotiropoulos, Georgios C; Li, Jun; Kornasiewicz, Oskar; Plöckinger, Ursula

    2010-01-01

    Background: The incidence of neuroendocrine tumours (NET) has increased over the past three decades. Hepatic metastases which occur in up to 75% of NET patients significantly worsen their prognosis. New imaging techniques with increasing sensitivity enabling tumour detection at an early stage have been developed. The treatment encompasses a panel of surgical and non-surgical modalities. Methods: This article reviews the published literature related to management of hepatic neuroendocrine metastases. Results: Abdominal computer tomography, magnetic resonance tomography and somatostatin receptor scintigraphy are widely accepted imaging modalities. Hepatic resection is the only potentially curative treatment. Liver transplantation is justified in highly selected patients. Liver-directed interventional techniques and locally ablative measures offer effective palliation. Promising novel therapeutic options offering targeted approaches are under evaluation. Conclusions: The treatment of neuroendocrine liver metastases still needs to be standardized. Management in centres of expertise should be strongly encouraged in order to enable a multidisciplinary approach and personalized treatment. Development of molecular prognostic factors to select treatment according to patient risk should be attempted. PMID:20662787

  3. Single cell optical transfection.

    PubMed

    Stevenson, David J; Gunn-Moore, Frank J; Campbell, Paul; Dholakia, Kishan

    2010-06-01

    The plasma membrane of a eukaryotic cell is impermeable to most hydrophilic substances, yet the insertion of these materials into cells is an extremely important and universal requirement for the cell biologist. To address this need, many transfection techniques have been developed including viral, lipoplex, polyplex, capillary microinjection, gene gun and electroporation. The current discussion explores a procedure called optical injection, where a laser field transiently increases the membrane permeability to allow species to be internalized. If the internalized substance is a nucleic acid, such as DNA, RNA or small interfering RNA (siRNA), then the process is called optical transfection. This contactless, aseptic, single cell transfection method provides a key nanosurgical tool to the microscopist-the intracellular delivery of reagents and single nanoscopic objects. The experimental possibilities enabled by this technology are only beginning to be realized. A review of optical transfection is presented, along with a forecast of future applications of this rapidly developing and exciting technology. PMID:20064901

  4. Ultrasound mediated gene transfection

    NASA Astrophysics Data System (ADS)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

    2002-05-01

    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  5. Graphene based gene transfection

    NASA Astrophysics Data System (ADS)

    Feng, Liangzhu; Zhang, Shuai; Liu, Zhuang

    2011-03-01

    Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI-10k polymer. The positively charged GO-PEI complexes are able to further bind with plasmid DNA (pDNA) for intracellular transfection of the enhanced green fluorescence protein (EGFP) gene in HeLa cells. While EGFP transfection with PEI-1.2k appears to be ineffective, high EGFP expression is observed using the corresponding GO-PEI-1.2k as the transfection agent. On the other hand, GO-PEI-10k shows similar EGFP transfection efficiency but lower toxicity compared with PEI-10k. Our results suggest graphene to be a novel gene delivery nano-vector with low cytotoxicity and high transfection efficiency, promising for future applications in non-viral based gene therapy.Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI

  6. Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

    PubMed

    Hatton, M Q; Reed, N S

    1997-01-01

    The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity. PMID:9448967

  7. Endoscopic mucosal resection of early stage colon neuroendocrine carcinoma.

    PubMed

    Yamasaki, Yasushi; Uedo, Noriya; Ishihara, Ryu; Tomita, Yasuhiko

    2015-01-01

    Early stage colorectal neuroendocrine carcinoma is rare. A small colon tumour was found in a 56-year-old man during diagnostic colonoscopy performed after a positive faecal occult blood test, and he was referred for treatment. A slightly reddish superficial elevated lesion with a shallow depression 10 mm in size was found in the transverse colon. Magnifying narrow-band imaging revealed disrupted irregular microvessels and the absence of a surface pattern in the depressed area. En bloc endoscopic mucosal resection (EMR) of the tumour was undertaken. The tumour was positive for chromogranin A and synaptophysin, and had a mitotic rate of >20/10 high-power fields and a Ki-67 proliferative index of >50%; it was diagnosed as a neuroendocrine carcinoma. The tumour minimally invaded the submucosa (300 μm) without lymphovascular involvement. The patient was followed up carefully, and at 1 year after EMR, no recurrence was found using colonoscopy and CT scans. PMID:25737221

  8. Neuroendocrine mechanisms in athletes.

    PubMed

    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. PMID:25248600

  9. Neuroendocrine Role for VGF

    PubMed Central

    Lewis, Jo E.; Brameld, John M.; Jethwa, Preeti H.

    2015-01-01

    The vgf gene (non-acronymic) is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain-derived neurotrophic factor, and glial-derived growth factor. The VGF gene gives rise to a 68 kDa precursor polypeptide, which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific prohormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly in the hypothalamus and hippocampus, in peripheral tissues including the pituitary gland, the adrenal glands, and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles, and in this review, we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction, and cognition. PMID:25699015

  10. In vivo photoacoustic imaging of tyrosinase expressing tumours in mice

    NASA Astrophysics Data System (ADS)

    Laufer, Jan; Jathoul, Amit; Johnson, Peter; Zhang, Edward; Lythgoe, Mark; Pedley, R. Barbara; Pule, Martin; Beard, Paul

    2012-02-01

    Two human tumour cell lines (K562, 293T) were stably transfected to achieve the genetic expression of tyrosinase, which is involved in the production of the pigment eumelanin. The cells were injected subcutaneously into nude mice to form tumour xenografts, which were imaged over a period of up to 26 days using an all-optical photoacoustic imaging system. 3D photoacoustic images of the tumours and the surrounding vasculature were acquired at excitation wavelengths ranging from 600nm to 770nm. The images showed tumour growth and continued tyrosinase expression over the full 26 day duration of the study. These findings were confirmed by histological analysis of excised tumour samples.

  11. Transfection of Platyhelminthes

    PubMed Central

    Moguel, Bárbara; Bobes, Raúl J.; Carrero, Julio C.; Laclette, Juan P.

    2015-01-01

    Flatworms are one of the most diverse groups within Lophotrochozoa with more than 20,000 known species, distributed worldwide in different ecosystems, from the free-living organisms in the seas and lakes to highly specialized parasites living in a variety of hosts, including humans. Several infections caused by flatworms are considered major neglected diseases affecting countries in the Americas, Asia, and Africa. For several decades, a particular interest on free-living flatworms was due to their ability to regenerate considerable portions of the body, implying the presence of germ cells that could be important for medicine. The relevance of reverse genetics for this group is clear; understanding the phenotypic characteristics of specific genes will shed light on developmental traits of free-living and parasite worms. The genetic manipulation of flatworms will allow learning more about the mechanisms for tissue regeneration, designing new and more effective anthelmintic drugs, and explaining the host-parasite molecular crosstalk so far partially inaccessible for experimentation. In this review, availability of transfection techniques is analyzed across flatworms, from the initial transient achievements to the stable manipulations now developed for free-living and parasite species. PMID:26090388

  12. [Grading of neuroendocrine tumors].

    PubMed

    Saeger, W; Schnabel, P A; Komminoth, P

    2016-07-01

    The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, <2 per 10 high-power fields (HPF) and the Ki-67 (index <3 %) and G2 tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems. PMID:27379621

  13. Endocannabinoid Regulation of Neuroendocrine Systems.

    PubMed

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

    2015-01-01

    The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus. Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems. Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function. Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C. The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964). PMID:26638767

  14. Current Concepts in Neuroendocrine Disruption

    PubMed Central

    2014-01-01

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

  15. [Pancreatic neuroendocrine neoplasms].

    PubMed

    Beiderwellen, K; Sabet, A; Lauenstein, T C; Lahner, H; Poeppel, T D

    2016-04-01

    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. PMID:27003413

  16. Neuroendocrine Responses to Hypoglycemia

    PubMed Central

    Tesfaye, Nolawit; Seaquist, Elizabeth R.

    2010-01-01

    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. PMID:21039590

  17. Neuroendocrine targets of endocrine disruptors

    PubMed Central

    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, and 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 systems, 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 sequelae on endocrine and reproductive functions. PMID:20363718

  18. Carcinoid tumour of the common bile duct--a novel complication of von Hippel-Lindau syndrome.

    PubMed Central

    Fellows, I W; Leach, I H; Smith, P G; Toghill, P J; Doran, J

    1990-01-01

    A 30 year old man with von Hippel-Lindau syndrome presented with obstructive jaundice caused by a carcinoid tumour of the mid- and upper common bile duct. This association is probably causally related in view of the propensity for patients with von Hippel-Lindau syndrome to develop neuroendocrine tumours. Images Figure 1 Figure 2 PMID:2379881

  19. Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia.

    PubMed

    Karpińska-Kaczmarczyk, K; Lewandowska, M; Białek, A; Ławniczak, M; Urasińska, E

    2016-03-01

    Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions. PMID:27179272

  20. Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine

    PubMed Central

    Casey, David G; Lysaght, Joanne; James, Tharappel; Bateman, Andrew; Melcher, Alan A; Todryk, Stephen M

    2003-01-01

    Antigenic cross-reactivity between certain tumours has allowed the development of more widely applicable, major histocompatibility complex-disparate (allogeneic) whole-cell vaccines. This principle should also allow heat shock proteins (hsp) derived from certain tumours (and carrying cross-reactive antigens) to be used as vaccines to generate anti-tumour immunity in a range of cancer patients. Here, hsp70 derived from gp70-antigen+ B16 melanoma generated cytotoxic-T-lymphocyte-mediated immune protection in BALB/c mice against challenge with gp70-antigen+ CT26 colorectal tumour cells. Using ovalbumin as a model tumour antigen, it is shown that hsp70 enhances peptide re-presentation by dendritic cells via class I over equimolar whole ovalbumin antigen. However, while transfection of tumour cells with inducible hsp70 increases hsp yield from tumours, it does not enhance antigen recognition via purified hsp70 nor via whole cells or their lysate. PMID:12941147

  1. Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

    ClinicalTrials.gov

    2015-10-15

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

  2. Integrated Electrowetting Nanoinjector for Single Cell Transfection

    PubMed Central

    Shekaramiz, Elaheh; Varadarajalu, Ganeshkumar; Day, Philip J.; Wickramasinghe, H. Kumar

    2016-01-01

    Single cell transfection techniques are essential to understand the heterogeneity between cells. We have developed an integrated electrowetting nanoinjector (INENI) to transfect single cells. The high transfection efficiency, controlled dosage delivery and ease of INENI fabrication promote the widespread application of the INENI in cell transfection assays. PMID:27374766

  3. Neuroendocrine control of satiation.

    PubMed

    Asarian, Lori; Bächler, Thomas

    2014-09-01

    Abstract Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms. PMID:25390024

  4. [Management of neuroendocrine prostate carcinoma: Literature review].

    PubMed

    Yossi, S; Brahmi, T; Enachescu, C; Selmaji, I; Lapierre, A; Samlali, H; Chapet, O

    2016-06-01

    Neuroendocrine prostate carcinoma is a rare entity causing both diagnostic and therapeutic issues. There are basically four histological forms (adenocarcinoma with neuroendocrine differentiation, carcinoid tumors, small cell neuroendocrine carcinomas, large cell neuroendocrine carcinomas), which can be pure or mixed associated with prostatic carcinoma. There is no consensus on the management or the prognosis of these various tumor subtypes. We conducted a literature review aiming to determine the potential therapeutic implications. PMID:27340027

  5. Histopathology of gastrointestinal neuroendocrine neoplasms

    PubMed Central

    Hirabayashi, Kenichi; Zamboni, Giuseppe; Nishi, Takayuki; Tanaka, Akira; Kajiwara, Hiroshi; Nakamura, Naoya

    2013-01-01

    Gastrointestinal neuroendocrine neoplasms (GI-NENs) arise from neuroendocrine cells distributed mainly in the mucosa and submucosa of the gastrointestinal tract. In 2010, the World Health Organization (WHO) classification of NENs of the digestive system was changed, categorizing these tumors as grade 1 neuroendocrine tumor (NET), grade-2NET, neuroendocrine carcinoma (large- or small-cell type), or mixed adenoneuroendocrine carcinoma (MANEC). Such a classification is based on the Ki-67 index and mitotic count in histological material. For the accurate pathological diagnosis and grading of NENs, it is important to clearly recognize the characteristic histological features of GI-NENs and to understand the correct method of counting Ki-67 and mitoses. In this review, we focus on the histopathological features of GI-NENs, particularly regarding biopsy and cytological diagnoses, neuroendocrine markers, genetic and molecular features, and the evaluation of the Ki-67 index and mitotic count. In addition, we will address the histological features of GI-NEN in specific organs. PMID:23346552

  6. Histopathology of gastrointestinal neuroendocrine neoplasms.

    PubMed

    Hirabayashi, Kenichi; Zamboni, Giuseppe; Nishi, Takayuki; Tanaka, Akira; Kajiwara, Hiroshi; Nakamura, Naoya

    2013-01-01

    Gastrointestinal neuroendocrine neoplasms (GI-NENs) arise from neuroendocrine cells distributed mainly in the mucosa and submucosa of the gastrointestinal tract. In 2010, the World Health Organization (WHO) classification of NENs of the digestive system was changed, categorizing these tumors as grade 1 neuroendocrine tumor (NET), grade-2NET, neuroendocrine carcinoma (large- or small-cell type), or mixed adenoneuroendocrine carcinoma (MANEC). Such a classification is based on the Ki-67 index and mitotic count in histological material. For the accurate pathological diagnosis and grading of NENs, it is important to clearly recognize the characteristic histological features of GI-NENs and to understand the correct method of counting Ki-67 and mitoses. In this review, we focus on the histopathological features of GI-NENs, particularly regarding biopsy and cytological diagnoses, neuroendocrine markers, genetic and molecular features, and the evaluation of the Ki-67 index and mitotic count. In addition, we will address the histological features of GI-NEN in specific organs. PMID:23346552

  7. An Ectopic ACTH Secreting Metastatic Parotid Tumour

    PubMed Central

    Dacruz, Thomas; Kalhan, Atul; Rashid, Majid; Obuobie, Kofi

    2016-01-01

    A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5–10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH. PMID:26904316

  8. An Ectopic ACTH Secreting Metastatic Parotid Tumour.

    PubMed

    Dacruz, Thomas; Kalhan, Atul; Rashid, Majid; Obuobie, Kofi

    2016-01-01

    A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5-10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH. PMID:26904316

  9. Neuroendocrine effects of light

    NASA Astrophysics Data System (ADS)

    Reiter, Russel J.

    1991-09-01

    The light/dark cycle to which animals, and possibly humans, are exposed has a major impact on their physiology. The mechanisms whereby specific tissues respond to the light/dark cycle involve the pineal hormone melatonin. The pineal gland, an end organ of the visual system in mammals, produces the hormone melatonin only at night, at which time it is released into the blood. The duration of elevated nightly melatonin provides every tissue with information about the time of day and time of year (in animals that are kept under naturally changing photoperiods). Besides its release in a circadian mode, melatonin is also discharged in a pulsatile manner; the physiological significance, if any, of pulsatile melatonin release remains unknown. The exposure of animals including man to light at night rapidly depresses pineal melatonin synthesis and, therefore, blood melatonin levels drop precipitously. The brightness of light at night required to depress melatonin production is highly species specific. In general, the pineal gland of nocturnally active mammals, which possess rod-dominated retinas, is more sensitive to inhibition by light than is the pineal gland of diurnally active animals (with cone-dominated retinas). Because of the ability of the light/dark cycle to determine melatonin production, the photoperiod is capable of influencing the function of a variety of endocrine and non-endocrine organs. Indeed, melatonin is a ubiquitously acting pineal hormone with its effects on the neuroendocrine system having been most thoroughly investigated. Thus, in nonhuman photoperiodic mammals melatonin regulates seasonal reproduction; in humans also, the indole has been implicated in the control of reproductive physiology.

  10. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    PubMed

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well

  11. Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent hypoglycemia: a diagnostic dilemma

    PubMed Central

    2014-01-01

    Background Hypoglycemia secondary to ectopic insulin secretion of non-pancreatic tumors is rare. Case presentation We describe a middle aged woman with recurrent hypoglycemia. On evaluation, she was detected to have hyperinsulinemic hypoglycemia and right sided renal mass lesion. 68Ga-Dotanoc and 99mTc-HYNICTOC scans confirmed the intrarenal mass to be of neuroendocrine origin. Right nephrectomy was done and it turned out to be an insulin secreting neuroendocrine tumour. Neuroendocrine nature of this tumour was further confirmed by ultra-structural examination. Her hypoglycemia did not recur after resection of this tumour. Conclusion Few cases of ectopic insulin secretion have been reported though some are not proven convincingly. This case addresses all the issues raised in previous case reports and proves by clinical, laboratory, functional imaging and immunohistochemical analysis that ectopic origin of insulin by non-pancreatic tumors does occur. To our knowledge, this is the first reported case of ectopic insulinoma arising from the kidney. PMID:24741994

  12. Transient transfection of purified Babesia bovis merozoites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transient transfection of intraerythrocytic Babesia bovis parasites has been previously reported. In this study, we describe the development and optimization of methods for transfection of purified B. bovis merozoites using either nucleofection (Amaxa) or conventional electroporation (Gene Pulser II...

  13. Expanding Therapy for Neuroendocrine Tumors.

    PubMed

    2016-03-01

    Results from two phase III studies suggest that everolimus, an mTOR inhibitor, and (177)Lutetium-DOTATATE, a radiopharmaceutical, may be effective new options for patients with advanced neuroendocrine tumors of the gastrointestinal tract. Both therapies were well tolerated and significantly prolonged progression-free survival. PMID:26826165

  14. Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

    ClinicalTrials.gov

    2016-03-18

    Poorly Differentiated Neuroendocrine Carcinoma,; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

  15. Neuroendocrine carcinoma of the cervix presenting as intractable hyponatremic seizures due to paraneoplastic SIADH—a rare case report and brief review of the literature

    PubMed Central

    Kuriakose, Santhosh; Umadevi, N; Mathew, Sheela; Supriya, NK; Aravindan, KP; Smitha, DS; Amritha Malini, G

    2014-01-01

    Herein is presented an interesting case of small-cell neuroendocrine carcinoma of the cervix which initially manifests as seizures due to hyponatremia caused by paraneoplastic syndrome of inappropriate anti diuretic hormone (SIADH). Awareness of a paraneoplastic syndrome at presentation can lead to early diagnosis and early initiation of treatment. The management is also unique in that it combines treating the paraneoplastic aspects as well as targeting the tumour itself. Multimodality treatment gives the best outcome in this aggressive tumour. PMID:25114722

  16. Notch Signaling in Neuroendocrine Tumors

    PubMed Central

    Crabtree, Judy S.; Singleton, Ciera S.; Miele, Lucio

    2016-01-01

    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 such as 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. PMID:27148486

  17. Molecular Imaging of Neuroendocrine Tumors

    PubMed Central

    Carrasquillo, Jorge A.; Chen, Clara C.

    2014-01-01

    Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals. PMID:21167384

  18. Pancreatic neuroendocrine tumors: Challenges in an underestimated disease.

    PubMed

    Viúdez, A; De Jesus-Acosta, A; Carvalho, F L; Vera, R; Martín-Algarra, S; Ramírez, N

    2016-05-01

    Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual oncologic entity. Due to its relative good prognosis, surgery remains the goal standard therapy not only in localized disease but also in the setting of locally or metastatic disease. Most of the patients are diagnosed in metastatic scenario, where multidisciplinary approach based on surgery, chemotherapies, liver-directed and/or molecular targeted therapies are commonly used. Owing to a deeper molecular knowledge of this disease, these targeted therapies are nowadays widely implemented, being the likely discovery of predictive biomarkers that would allow its use in other settings. This review is focused on describing the different classifications, etiology, prognostic biomarkers and multidisciplinary approaches that are typically used in PanNET. PMID:27021395

  19. Transfection in the third dimension

    PubMed Central

    Dhaliwal, Anandika; Oshita, Victor; Segura, Tatiana

    2013-01-01

    An understanding of parameters that modulate gene transfer in 3-D will assist in the formation of gene delivery systems and scaffolds, which can mediate efficient non-viral delivery for guiding in-vivo tissue regeneration and therapy. We have previously demonstrated the cell area and length, integrin expression, and RhoGTPases mediated signalling to be pivotal parameters that guide gene transfer to mouse mesenchymal stem cells (mMSCs) cultured in 2-D and are modulated by ECM proteins. In this study, we were interested in determining if cationic polymer mediated gene transfer to cells seeded in 3-D would occur through different mechanisms as compared to 2-D. In particular, we examined the endocytosis pathways used to internalize polyplexes, and the role of cytoskeletal dynamics and RhoGTPases on non-viral gene transfer for cells seeded in 2-D and 3-D. Inhibition of clathrin- and caveolae- mediated endocytosis resulted in more drastic decrease in overall transgene expression for cells seeded in 3-D than those in 2-D. In addition, polyplex internalization was only significantly decreased in 3-D when clathrin-mediated endocytosis was inhibited, while caveolae-mediated endocytosis inhibition for cells seeded in 2-D resulted in the strongest polyplex internalization inhibition. Actin and microtubule polymerization affected 2-D and 3-D transfection differently. Microtubule depolymerization enhanced transgene expression in 2-D, but inhibited transgene expression in 3-D. Last, inhibition of RhoGTPases also affected 2-D and 3-D transfection differently. The inhibition of ROCK effector resulted in a decrease of transgene expression and internalization for cells seeded in 3-D, but not 2-D and the inhibition of effector PAK1 resulted in an increase of transgene expression for both 2-D and 3-D. Overall, our study suggests that the process of gene transfer occurs through different mechanisms for cells seeded in 2-D compared to those seeded in 3-D. PMID:23929354

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

    PubMed

    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. PMID:27514602

  1. [Neuroendocrine system of the pancreas and gastrointestinal tract: origin and development].

    PubMed

    Díaz Pérez, José Angel

    2009-04-01

    Gastroenteropancreatic neuroendocrine tumours (GEP NETs) originate from the neuroendocrine cells through the gastrointestinal tract and endocrine pancreas. The embryologic development of the pancreas is a complex process that begins with the "stem cell" that come from the endodermus. These cells go through two phases: in the first transition the "stem cell" differentiates in exocrine and endocrine cells. This process is regulated by transcription factors such as Pdx1 ("insulin promoter factor 1"), Hlxb6 and SOX9. In the second transition the neuroendocrine cell differentiates in the 5 cell types (alpha, beta, delta, PP y epsilon.). This process is regulated through the balance between factors favoring differentiation (mainly neurogenin 3) and inhibitor factors which depend on Notch signals. The existence of a third transition in postnatal pancreas is hypothesized. The "stem cell" from pancreatic ducts would become adult beta cells, through autoduplication and neogenesis. In the small gut of the adult the stem cell are placed in the intestinal crypts and develop to villi in secretor lines (enterocytes, globet and Paneths cells) or neuroendocrine cells from which at least 10 cell types depend. This process is regulated by transcription factors: Math1, neurogenina 3 and NeuroD. PMID:19627763

  2. Irradiation Decreases the Neuroendocrine Biomarker Pro-Opiomelanocortin in Small Cell Lung Cancer Cells In Vitro and In Vivo

    PubMed Central

    Meredith, Suzanne L.; Bryant, Jennifer L.; Babur, Muhammad; Riddell, Philip W.; Behrouzi, Roya; Williams, Kaye J.; White, Anne

    2016-01-01

    Background Small cell lung cancer (SCLC) is an extremely aggressive disease, commonly displaying therapy-resistant relapse. We have previously identified neuroendocrine and epithelial phenotypes in SCLC tumours and the neuroendocrine marker, pro-opiomelanocortin (POMC), correlated with worse overall survival in patients. However, the effect of treatment on these phenotypes is not understood. The current study aimed to determine the effect of repeated irradiation treatment on SCLC cell phenotype, focussing on the neuroendocrine marker, POMC. Results Human SCLC cells (DMS 79) were established as subcutaneous xenograft tumours in CBA nude mice and then exposed to repeated 2Gy irradiation. In untreated animals, POMC in the blood closely mirrored tumour growth; an ideal characteristic for a circulating biomarker. Following repeated localised irradiation in vivo, circulating POMC decreased (p< 0.01), in parallel with a decrease in tumour size, but remained low even when the tumours re-established. The excised tumours displayed reduced and distinctly heterogeneous expression of POMC compared to untreated tumours. There was no difference in the epithelial marker, cytokeratin. However, there were significantly more N-cadherin positive cells in the irradiated tumours. To investigate the tumour response to irradiation, DMS79 cells were repeatedly irradiated in vitro and the surviving cells selected. POMC expression was reduced, while mesenchymal markers N-cadherin, β1-integrin, fibroblast-specific protein 1, β-catenin and Zeb1 expression were amplified in the more irradiation-primed cells. There were no consistent changes in epithelial marker expression. Cell morphology changed dramatically with repeatedly irradiated cells displaying a more elongated shape, suggesting a switch to a more mesenchymal phenotype. Conclusions In summary, POMC biomarker expression and secretion were reduced in SCLC tumours which regrew after irradiation and in repeatedly irradiation (irradiation

  3. Neuroendocrine neoplasms of the sinonasal region.

    PubMed

    Bell, Diana; Hanna, Ehab Y; Weber, Randal S; DeMonte, Franco; Triantafyllou, Asterios; Lewis, James S; Cardesa, Antonio; Slootweg, Pieter J; Stenman, Göran; Gnepp, Douglas R; Devaney, Kenneth O; Rodrigo, Juan P; Rinaldo, Alessandra; Wenig, Bruce M; Westra, William H; Bishop, Justin A; Hellquist, Henrik; Hunt, Jennifer L; Kusafuka, Kimihide; Perez-Ordoñez, Bayardo; Williams, Michelle D; Takes, Robert P; Ferlito, Alfio

    2016-04-01

    Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016. PMID:26041714

  4. Immunocytochemical analysis of the tissue location of cytokines (IL-2 and IL-12) in neuroendocrine lung cancer.

    PubMed

    Kasprzak, Aldona; Przewoźna, Mariola; Zabel, Maciej; Pankowski, Juliusz; Surdyk-Zasada, Joanna

    2003-01-01

    The study aimed at immunocytochemical evaluation of the cellular expression of two cytokines, IL-2 and IL-12 in lung carcinoids (n = 10), following the earlier demonstration of two markers of endocrine tumours (chromogranin A and NSE--neuron-specific enolase). In the immunocytochemical studies the classical avidin-biotinylated peroxidase (ABC) technique was used. Results of the tests were semiquantitatively appraised employing the IRS scale. In 9/10 cases intense reaction (score: 6-12 points) was noted for both lung neuroendocrine markers. In all cases of carcinoma co-expression of IL-2 and IL-12 was demonstrated in cells of the tumours. The cytokines showed a cytoplasmic localisation of mean (score: 3-4 points) or high (score: 6-12 points) intensity of reaction. Our studies point to a possible role of the two cytokines in the proliferation of lung neuroendocrine carcinomas but more detailed analysis is required on a broader material. PMID:14507073

  5. TRANSFECTION OF INSECT CELL LINES USING POLYETHYLENIMINE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect cell lines have been widely used in recombinant baculovirus expression systems and transient gene expression studies. Critical to these applications have been the transfection of foreign DNA. This has been widely done using labor intensive and cytotoxic liposome-based transfection reagents....

  6. Neuroendocrine Regulation of Maternal Behavior

    PubMed Central

    Bridges, Robert S.

    2015-01-01

    The expression of maternal behavior in mammals is regulated by the developmental and experiential events over a female’s lifetime. In this review the relationships between the endocrine and neural systems that play key roles in these developmental and experiential that affect both the establishment and maintenance of maternal care are presented. The involvement of the hormones estrogen, progesterone, and lactogens are discussed in the context of ligand, receptor, and gene activity in rodents and to a lesser extent in higher mammals. The roles of neuroendocrine factors, including oxytocin, vasopressin, classical neurotransmitters, and other neural gene products that regulate aspects of maternal care are set forth, and the interactions of hormones with central nervous system mediators of maternal behavior are discussed. The impact of prior developmental factors, including epigenetic events, and maternal experience on subsequent maternal care are assessed over the course of the female’s lifespan. It is proposed that common neuroendocrine mechanisms underlie the regulation of maternal care in mammals. PMID:25500107

  7. High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

    PubMed

    Cigrovski Berković, Maja; Čačev, Tamara; Catela Ivković, Tina; Marout, Jasminka; Ulamec, Monika; Zjačić-Rotkvić, Vanja; Kapitanović, Sanja

    2016-04-15

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascularized neoplasms, capable of synthethisizing VEGF-A, a key mediator of angiogenesis. In pancreatic neuroendocrine tumors (pNETs) VEGF expression is higher in benign and low-grade tumors and associated with good prognosis (neuroendocrine paradox) while the VEGF role in gastrointestinal NETs (GI-NETs) is still unclear. In this study, we examined the VEGF-1154A/G polymorphism in 145 GEP-NET patients and 150 controls. Next, we measured VEGF serum levels and VEGF tumor protein expression, comparing it with Ki67 and tumor grade. Patients' VEGF serum levels were compared with VEGF -1145A/G genotypes and metastatic status as well as with chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA) in case of GI-NET patients. In this study GEP-NET patients had elevated VEGF serum values when compared to healthy controls (p = 0.0013). VEGF-1145G allele correlated with higher VEGF serum levels (p = 0.002). Patients with metastatic tumors had higher VEGF serum values when compared to patients without metastases (p = 0.033), and highest levels were observed in case of lymph node metastases (p = 0.008). VEGF-1145G allele was more frequent in non-functional GI-NET patients than in healthy controls (p = 0.041). CgA was superior to VEGF in tumor detection, while VEGF was superior to 5-HIAA. A correlation was observed between VEGF immunohistochemical staining and Ki-67 (p = 0.028). Tumours with weaker VEGF protein expression were more aggressive than tumours with stronger VEGF expression, confirming a "neuroendocrine paradox" in GI-NETs. Our results suggest the role of VEGF in GI-NETs locoregional spread. PMID:26805636

  8. Brain and spinal tumour.

    PubMed

    Goh, C H; Lu, Y Y; Lau, B L; Oy, J; Lee, H K; Liew, D; Wong, A

    2014-12-01

    This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning. PMID:25934956

  9. Optimization of Gene Transfection in Murine Myeloma Cell Lines using Different Transfection Reagents

    PubMed Central

    Shabani, Mahdi; Hemmati, Sheyda; Hadavi, Reza; Amirghofran, Zahra; Jeddi-Tehrani, Mahmood; Rabbani, Hodjatallah; Shokri, Fazel

    2010-01-01

    Purification and isolation of cellular target proteins for monoclonal antibody (MAb) production is a difficult and time-consuming process. Immunization of mice with murine cell lines stably transfected with genes coding for xenogenic target molecules is an alternative method for mouse immunization and MAb production. Here we present data on transfection efficiency of some commercial reagents used for transfection of murine myeloma cell lines. Little is known about transfectability of murine myeloma cell lines by different transfection reagents. Mouse myeloma cell lines (SP2/0, NS0, NS1, Ag8, and P3U1) were transfected with pEGFP-N1 vector using Lipofectamine 2000, jetPEI and LyoVec commercial transfection reagents in different combinations. The transfection permissible HEK293-FT cell line was used as a control in transfection procedure. Transfected cells, expressing the Enhanced Green Fluorescent Protein (EGFP), were analyzed by flow cytometry 48 hrs post transfection. Our results showed transfection efficiency of 71%, 57% and 22% for HEK293-FT, 5.5%, 3.4% and 1% for SP2/0, 55.7%, 21.1% and 9.3% for NS0, 8.2%, 6% and 5.5% for NS1, 22%, 49.2% and 5.5% for Ag8 and 6.3%, 21.5% and 4.6% for P3U1 cell lines after transfection with Lipofectamine 2000, jetPEI and LyoVec reagents, respectively. Our data indicate that NS0 and Ag8 are efficiently transfected by Lipofectamine 2000 and jetPEI reagents. Finally, we propose Ag8 and NS0 cell lines as suitable host cells for efficient expression of target genes which can be used for mouse immunization and MAb production. PMID:23408356

  10. Optimization of Gene Transfection in Murine Myeloma Cell Lines using Different Transfection Reagents.

    PubMed

    Shabani, Mahdi; Hemmati, Sheyda; Hadavi, Reza; Amirghofran, Zahra; Jeddi-Tehrani, Mahmood; Rabbani, Hodjatallah; Shokri, Fazel

    2010-07-01

    Purification and isolation of cellular target proteins for monoclonal antibody (MAb) production is a difficult and time-consuming process. Immunization of mice with murine cell lines stably transfected with genes coding for xenogenic target molecules is an alternative method for mouse immunization and MAb production. Here we present data on transfection efficiency of some commercial reagents used for transfection of murine myeloma cell lines. Little is known about transfectability of murine myeloma cell lines by different transfection reagents. Mouse myeloma cell lines (SP2/0, NS0, NS1, Ag8, and P3U1) were transfected with pEGFP-N1 vector using Lipofectamine 2000, jetPEI and LyoVec commercial transfection reagents in different combinations. The transfection permissible HEK293-FT cell line was used as a control in transfection procedure. Transfected cells, expressing the Enhanced Green Fluorescent Protein (EGFP), were analyzed by flow cytometry 48 hrs post transfection. Our results showed transfection efficiency of 71%, 57% and 22% for HEK293-FT, 5.5%, 3.4% and 1% for SP2/0, 55.7%, 21.1% and 9.3% for NS0, 8.2%, 6% and 5.5% for NS1, 22%, 49.2% and 5.5% for Ag8 and 6.3%, 21.5% and 4.6% for P3U1 cell lines after transfection with Lipofectamine 2000, jetPEI and LyoVec reagents, respectively. Our data indicate that NS0 and Ag8 are efficiently transfected by Lipofectamine 2000 and jetPEI reagents. Finally, we propose Ag8 and NS0 cell lines as suitable host cells for efficient expression of target genes which can be used for mouse immunization and MAb production. PMID:23408356

  11. Mixed Adenoneuroendocrine Carcinoma Is a Rare but Important Tumour Found in the Oesophagus.

    PubMed

    Kadhim, Mohammad Murad Kasim; Jespersen, Marie Louise; Pilegaard, Hans Kristian; Nordsmark, Marianne; Villadsen, Gerda Elisabeth

    2016-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumour. We report a case of a 68-year-old man who presented with two-month history of postprandial pain and vomiting. Gastric endoscopy revealed a polypoid mass in the lower part of the oesophagus. In contrast to the majority of these tumours, this biopsy was immunohistochemically positive for chromogranin A, and synaptophysin and Ki-67 index was 50% and the tumour was diagnosed as poorly differentiated neuroendocrine carcinoma of the oesophagus. The patient underwent surgery and lower oesophagus resection was performed. Based on the histopathology and immunohistochemistry of the tumour in the oesophagogastrectomy specimen, a mixed adenoneuroendocrine carcinoma (MANEC) was diagnosed. The objective of this case report is to advocate for the focus on the MANEC diagnosis as such patients need to be referred to a centre of excellence with expertise in NET tumours, to have the correct diagnostic work-up, treatment, and secondary diagnostic procedures performed at progression, as this will have paramount influence of the choice of treatment. PMID:26955490

  12. Mixed Adenoneuroendocrine Carcinoma Is a Rare but Important Tumour Found in the Oesophagus

    PubMed Central

    Kadhim, Mohammad Murad Kasim; Jespersen, Marie Louise; Pilegaard, Hans Kristian; Nordsmark, Marianne; Villadsen, Gerda Elisabeth

    2016-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumour. We report a case of a 68-year-old man who presented with two-month history of postprandial pain and vomiting. Gastric endoscopy revealed a polypoid mass in the lower part of the oesophagus. In contrast to the majority of these tumours, this biopsy was immunohistochemically positive for chromogranin A, and synaptophysin and Ki-67 index was 50% and the tumour was diagnosed as poorly differentiated neuroendocrine carcinoma of the oesophagus. The patient underwent surgery and lower oesophagus resection was performed. Based on the histopathology and immunohistochemistry of the tumour in the oesophagogastrectomy specimen, a mixed adenoneuroendocrine carcinoma (MANEC) was diagnosed. The objective of this case report is to advocate for the focus on the MANEC diagnosis as such patients need to be referred to a centre of excellence with expertise in NET tumours, to have the correct diagnostic work-up, treatment, and secondary diagnostic procedures performed at progression, as this will have paramount influence of the choice of treatment. PMID:26955490

  13. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  14. Update on pancreatic neuroendocrine tumors

    PubMed Central

    McKenna, Logan R.

    2014-01-01

    Pancreatic neuroendocrine tumors (pNETs) are relatively rare tumors comprising 1-2% of all pancreas neoplasms. In the last 10 years our understanding of this disease has increased dramatically allowing for advancements in the treatment of pNETs. Surgical excision remains the primary therapy for localized tumors and only potential for cure. New surgical techniques using laparoscopic approaches to complex pancreatic resections are a major advancement in surgical therapy and increasingly possible. With early detection being less common, most patients present with metastatic disease. Management of these patients requires multidisciplinary care combining the best of surgery, chemotherapy and other targeted therapies. In addition to surgical advances, recently, there have been significant advances in systemic therapy and targeted molecular therapy. PMID:25493258

  15. Some aspects of neuroendocrine pathology.

    PubMed Central

    Polak, J M; Bloom, S R

    1987-01-01

    The advent of modern microscopical investigative methods for the determination of neuroendocrine differentiation has increasingly given credence to the original concept of a "diffuse endocrine system". These methods include a variety of silver impregnation techniques, technologically advanced light and electron microscopical immunocytochemistry, and, lately, the ability to localise specific binding sites by in vitro autoradiography and mRNA species by in situ hybridisation. Further insight has been gained into the possible role of regulatory peptides contained in the so called "diffuse endocrine system" and into the nature of disease processes by investigating the role of the system in benign and malignant disease. Images Fig 13 Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 Fig 12 Fig 14 Fig 15 PMID:3312297

  16. Neuroendocrine Cancer of Rectum Metastasizing to Ovary.

    PubMed

    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

  17. Neuroendocrine Cancer of Rectum Metastasizing to Ovary

    PubMed Central

    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

  18. Development of the Neuroendocrine Hypothalamus.

    PubMed

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-01-01

    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. © 2016 American Physiological Society. Compr Physiol 6:623-643, 2016. PMID:27065164

  19. Tumours of the lung

    PubMed Central

    Stünzi, H.; Head, K. W.; Nielsen, S. W.

    1974-01-01

    Lung tumours are not common in domestic animals; there has not been the increase in epidermoid carcinomas and anaplastic small-cell carcinomas that has occurred in man this century. Adenocarcinoma is the most common type in animals. The biological behaviour of each type of tumour in animals seems to be much the same as in man. The tumours are described histologically, the main categories being: epidermoid carcinoma, anaplastic carcinoma, adenocarcinoma, combined epidermoid and adenocarcinoma, carcinoid tumours, bronchial gland tumours, benign tumours, and sarcomas. ImagesFig. 13Fig. 14Fig. 15Fig. 16Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:4371738

  20. Improved Biolistic Transfection of Hair Cells

    PubMed Central

    Gillespie, Peter G.

    2012-01-01

    Transient transfection of hair cells has proven challenging. Here we describe modifications to the Bio-Rad Helios Gene Gun that, along with an optimized protocol, improve transfection of bullfrog, chick, and mouse hair cells. The increased penetrating power afforded by our method allowed us to transfect mouse hair cells from the basal side, through the basilar membrane; this configuration protects hair bundles from damage during the procedure. We characterized the efficiency of transfection of mouse hair cells with fluorescently-tagged actin fusion protein using both the optimized procedure and a published procedure; while the efficiency of the two methods was similar, the morphology of transfected hair cells was improved with the new procedure. In addition, using the improved method, we were able to transfect hair cells in the bullfrog sacculus and chick cochlea for the first time. We used fluorescent-protein fusions of harmonin b (USH1C) and PMCA2 (ATP2B2; plasma-membrane Ca2+-ATPase isoform 2) to examine protein distribution in hair cells. While PMCA2-EGFP localization was similar to endogenous PMCA2 detected with antibodies, high levels of harmonin-EGFP were found at stereocilia tapers in bullfrog and chick, but not mouse; by contrast, harmonin-EGFP was concentrated in stereocilia tips in mouse hair cells. PMID:23049715

  1. Ballistic transfection of mammalian cells in vivo

    SciTech Connect

    Kolesnikov, V.A.; Zelenin, A.V.; Zelenina, I.A.

    1995-11-01

    The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Penetrating the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized, and this allowed the study of mammalian cells in situ. The performed studies allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase, and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ, and in developing mouse embryos at the stages of two-cell embryo, morula, and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was detected within two to three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated, and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail, and the published data on transfection and genetic transformation of mammalian cells are discussed. 41 refs., 13 figs., 1 tab.

  2. Improved biolistic transfection of hair cells.

    PubMed

    Zhao, Hongyu; Avenarius, Matthew R; Gillespie, Peter G

    2012-01-01

    Transient transfection of hair cells has proven challenging. Here we describe modifications to the Bio-Rad Helios Gene Gun that, along with an optimized protocol, improve transfection of bullfrog, chick, and mouse hair cells. The increased penetrating power afforded by our method allowed us to transfect mouse hair cells from the basal side, through the basilar membrane; this configuration protects hair bundles from damage during the procedure. We characterized the efficiency of transfection of mouse hair cells with fluorescently-tagged actin fusion protein using both the optimized procedure and a published procedure; while the efficiency of the two methods was similar, the morphology of transfected hair cells was improved with the new procedure. In addition, using the improved method, we were able to transfect hair cells in the bullfrog sacculus and chick cochlea for the first time. We used fluorescent-protein fusions of harmonin b (USH1C) and PMCA2 (ATP2B2; plasma-membrane Ca(2+)-ATPase isoform 2) to examine protein distribution in hair cells. While PMCA2-EGFP localization was similar to endogenous PMCA2 detected with antibodies, high levels of harmonin-EGFP were found at stereocilia tapers in bullfrog and chick, but not mouse; by contrast, harmonin-EGFP was concentrated in stereocilia tips in mouse hair cells. PMID:23049715

  3. Combining nebulization-mediated transfection and polymer microarrays for the rapid determination of optimal transfection substrates.

    PubMed

    Unciti-Broceta, Asier; Díaz-Mochón, Juan J; Mizomoto, Hitoshi; Bradley, Mark

    2008-01-01

    In this manuscript, we report how transfection efficiencies vary as a function of the substrate upon which cells adhere using a polymer microarray platform to allow rapid analysis of a large number of substrates. During these studies, traditional transfection protocols were nonsatisfactory, and thus we developed an approach in which an ultrasonic nebulizer was used to dispense lipoplexes onto cell-based microarrays in the absence of liquid. Under these conditions, droplets were directly deposited onto the cells thereby enhancing transfection. This approach was successfully applied to the transfection of various cell lines immobilized on a library of polyacrylates and permitted the identification of highly efficient transfection/polymer combinations, while showing that specific polymer-cell interactions may promote the efficacy of chemical transfection. PMID:18247582

  4. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  5. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  6. Tumour ablation: technical aspects

    PubMed Central

    Bodner, Gerd; Bale, Reto

    2009-01-01

    Abstract Image-guided percutaneous radiofrequency ablation (RFA) is a minimally invasive, relatively low-risk procedure for tumour treatment. Local recurrence and survival rates depend on the rate of complete ablation of the entire tumour including a sufficient margin of surrounding healthy tissue. Currently a variety of different RFA devices are available. The interventionalist must be able to predict the configuration and extent of the resulting ablation necrosis. Accurate planning and execution of RFA according to the size and geometry of the tumour is essential. In order to minimize complications, individualized treatment strategies may be necessary for tumours close to vital structures. This review examines the state-of-the art of different device technologies, approaches, and treatment strategies for percutaneous RFA of liver tumours. PMID:19965296

  7. Nanoparticles of compacted DNA transfect postmitotic cells.

    PubMed

    Liu, Ge; Li, DeShan; Pasumarthy, Murali K; Kowalczyk, Tomasz H; Gedeon, Christopher R; Hyatt, Susannah L; Payne, Jennifer M; Miller, Timothy J; Brunovskis, Peter; Fink, Tamara L; Muhammad, Osman; Moen, Robert C; Hanson, Richard W; Cooper, Mark J

    2003-08-29

    Charge-neutral DNA nanoparticles have been developed in which single molecules of DNA are compacted to their minimal possible size. We speculated that the small size of these DNA nanoparticles may facilitate gene transfer in postmitotic cells, permitting nuclear uptake across the 25-nm nuclear membrane pore. To determine whether DNA nanoparticles can transfect nondividing cells, growth-arrested neuroblastoma and hepatoma cells were transfected with DNA/liposome mixtures encoding luciferase. In both models, growth-arrested cells were robustly transfected by compacted DNA (6,900-360-fold more than naked DNA). To evaluate mechanisms responsible for enhanced transfection, HuH-7 cells were microinjected with naked or compacted plasmids encoding enhanced green fluorescent protein. Cytoplasmic microinjection of DNA nanoparticles generated a approximately 10-fold improvement in transgene expression as compared with naked DNA; this enhancement was reversed by the nuclear pore inhibitor, wheat germ agglutinin. To determine the upper size limit for gene transfer, DNA nanoparticles of various sizes were microinjected into the cytoplasm. A marked decrease in transgene expression was observed as the minor ellipsoidal diameter approached 25 nm. In summary, suitably sized DNA nanoparticles productively transfect growth arrested cells by traversing the nuclear membrane pore. PMID:12807905

  8. Neuroendocrine hormone amylin in diabetes

    PubMed Central

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

    2016-01-01

    The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and co-secreted 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 S20G 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. PMID:27162583

  9. Transgenerational neuroendocrine disruption of reproduction

    PubMed Central

    Walker, Deena M.; Gore, Andrea C.

    2014-01-01

    Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be ‘programmed’ through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes—namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents—and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants. PMID:21263448

  10. Primary Neuroendocrine Tumor in Brain

    PubMed Central

    Tamura, Ryota; Kuroshima, Yoshiaki; Nakamura, Yoshiki

    2014-01-01

    The incidence of brain metastases for neuroendocrine tumor (NET) is reportedly 1.5~5%, and the origin is usually pulmonary. A 77-year-old man presented to our hospital with headache and disturbance of specific skilled motor activities. Computed tomography (CT) showed a massive neoplastic lesion originating in the left temporal and parietal lobes that caused a mass edematous effect. Grossly, total resection of the tumor was achieved. Histological examination revealed much nuclear atypia and mitotic figures. Staining for CD56, chromogranin A, and synaptophysin was positive, indicating NET. The MIB-1 index was 37%. Histopathologically, the tumor was diagnosed as NET. After surgery, gastroscopy and colonoscopy were performed, but the origin was not seen. After discharge, CT and FDG-PET (fluoro-2-deoxy-d-glucose positron emission tomography) were performed every 3 months. Two years later we have not determined the origin of the tumor. It is possible that the brain is the primary site of this NET. To our knowledge, this is the first reported case of this phenomenon. PMID:25506006

  11. Neuroendocrine hormone amylin in diabetes.

    PubMed

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

    2016-05-10

    The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and co-secreted 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 S20G 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. PMID:27162583

  12. The Thymus–Neuroendocrine Axis

    PubMed Central

    Reggiani, Paula C.; Morel, Gustavo R.; Cónsole, Gloria M.; Barbeito, Claudio G.; Rodriguez, Silvia S.; Brown, Oscar A.; Bellini, Maria Jose; Pléau, Jean-Marie; Dardenne, Mireille; Goya, Rodolfo G.

    2009-01-01

    Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin. PMID:19236333

  13. Neuroendocrine Regulation of Hydromineral Homeostasis.

    PubMed

    Mecawi, Andre de Souza; Ruginsk, Silvia Graciela; Elias, Lucila Leico Kagohara; Varanda, Wamberto Antonio; Antunes-Rodrigues, Jose

    2015-07-01

    Since the crucial evolutionary change from an aqueous to a terrestrial environment, all living organisms address the primordial task of equilibrating the ingestion/production of water and electrolytes (primarily sodium) with their excretion. In mammals, the final route for the excretion of these elements is mainly through the kidneys, which can eliminate concentrated or diluted urine according to the requirements. Despite their primary role in homeostasis, the kidneys are not able to recover water and solutes lost through other systems. Therefore, the selective stimulation or inhibition of motivational and locomotor behavior becomes essential to initiate the search and acquisition of water and/or sodium from the environment. Indeed, imbalances affecting the osmolality and volume of body fluids are dramatic challenges to the maintenance of hydromineral homeostasis. In addition to behavioral changes, which are integrated in the central nervous system, most of the systemic responses recruited to restore hydroelectrolytic balance are accomplished by coordinated actions of the cardiovascular, autonomic and endocrine systems, which determine the appropriate renal responses. The activation of sequential and redundant mechanisms (involving local and systemic factors) produces accurate and self-limited effector responses. From a physiological point of view, understanding the mechanisms underlying water and sodium balance is intriguing and of great interest for the biomedical sciences. Therefore, the present review will address the biophysical, evolutionary and historical perspectives concerning the integrative neuroendocrine control of hydromineral balance, focusing on the major neural and endocrine systems implicated in the control of water and sodium balance. PMID:26140725

  14. Duodenal Neuroendocrine Tumors: Location Matters!

    PubMed

    Sheikh, Mohd Raashid; Osman, Houssam; Cheek, Susannah; Hunter, Shanee; Jeyarajah, Dhiresh Rohan

    2016-05-01

    Duodenal neuroendocrine tumors (NETs) are rare. Historically, when feasible a less aggressive surgical approach is considered. The aim of this study was to identify factors associated with prognosis and the necessity for more aggressive surgical procedures. All patients who underwent surgery for duodenal NETs between September 2005 and June 2014 were identified retrospectively. Data collected included clinical presentation, operative findings, and histopathological data. Eighteen patients underwent surgical management for duodenal NETs. Two patients underwent transduodenal excision (11%), two patients had partial duodenal resection (11%), two patients had antrectomy including 1st part of duodenum (D1) resection (33%), and eight underwent pancreaticoduodenectomy [PD (44%)]. On analysis, 2nd part of duodenum (D2) location was the most common site of duodenal NETs (n = 9, 50%). The odds of having a PD were 10 times higher when the lesion was in D2 location. The odds of having a positive lymph node are nine times higher when the lesion is in D2 region. The odds of having a positive lymph node are three times higher when lesion is greater than T1. D2 location of NETs is associated with higher odds of lymph node positivity and need for more extensive procedures like PD. PMID:27215716

  15. Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review

    PubMed Central

    Chun, Yi Kyeong

    2015-01-01

    Neuroendocrine tumors of the female reproductive tract are a heterogeneous group of neoplasms that display various histologic findings and biologic behaviors. In this review, the classification and clinicopathologic characteristics of neuroendocrine tumors of the female reproductive tract are described. Differential diagnoses are discussed, especially for non-neuroendocrine tumors showing high-grade nuclei with neuroendocrine differentiation. This review also discusses recent advances in our pathogenetic understanding of these disorders. PMID:26459408

  16. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

    Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

    2006-01-01

    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.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

  17. A bipartite graph of Neuroendocrine System

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  18. Bacterial-mediated DNA delivery to tumour associated phagocytic cells.

    PubMed

    Byrne, W L; Murphy, C T; Cronin, M; Wirth, T; Tangney, M

    2014-12-28

    Phagocytic cells including macrophages, dendritic cells and neutrophils are now recognised as playing a negative role in many disease settings including cancer. In particular, macrophages are known to play a pathophysiological role in multiple diseases and present a valid and ubiquitous therapeutic target. The technology to target these phagocytic cells in situ, both selectively and efficiently, is required in order to translate novel therapeutic modalities into clinical reality. We present a novel delivery strategy using non-pathogenic bacteria to effect gene delivery specifically to tumour-associated phagocytic cells. Non-invasive bacteria lack the ability to actively enter host cells, except for phagocytic cells. We exploit this natural property to effect 'passive transfection' of tumour-associated phagocytic cells following direct administration of transgene-loaded bacteria to tumour regions. Using an in vitro-differentiated human monocyte cell line and two in vivo mouse models (an ovarian cancer ascites and a solid colon tumour model) proof of delivery is demonstrated with bacteria carrying reporter constructs. The results confirm that the delivery strategy is specific for phagocytic cells and that the bacterial vector itself recruits more phagocytic cells to the tumour. While proof of delivery to phagocytic cells is demonstrated in vivo for solid and ascites tumour models, this strategy may be applied to other settings, including non-cancer related disease. PMID:25466954

  19. Experimental research on wild-type p53 plasmid transfected into retinoblastoma cells and tissues using an ultrasound microbubble intensifier.

    PubMed

    Luo, J; Zhou, X; Diao, L; Wang, Z

    2010-01-01

    The transfection efficiency of wild-type p53 (wtp53) was investigated in retinoblastoma (RB) Y79 cells using an ultrasound microbubble technique. A human RB nude mouse xenograft tumour model was also used to investigate whether this technique could deliver wtp53 into solid tumours. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that wtp53 was successfully transfected into Y79 cells in the plasmid with microbubbles and ultrasound group and in the plasmid with liposomes group, but not in the plasmid with ultrasound group or in the untreated control group. Flow cytometry showed that apoptosis was highest in the microbubbles and ultrasound group (25.58%) compared with the plasmid with liposomes group (19.50%), and the other two groups (< 10%). RT-PCR also showed that the wtp53 gene was successfully transfected into solid tumours in the plasmid with microbubbles and ultrasound group. This study provides preliminary evidence in support of a potential new approach to RB gene therapy. PMID:20819437

  20. Structural pathology underlying neuroendocrine dysfunction in schizophrenia

    PubMed Central

    Goldman, Morris B.; Wang, Lei; Wachi, Carly; Daudi, Sheeraz; Csernansky, John; Marlow-O'Connor, Megan; Keedy, Sarah; Torres, Ivan

    2010-01-01

    Polydipsic hyponatremic schizophrenic (PHS) patients exhibit altered neuroendocrine activity that has been linked to their life-threatening water imbalance, as well as to impaired function and reduced volume of the anterior hippocampus. Polydipsic patients without hyponatremia (polydipsic normonatremic schizophrenics: PNS) exhibit similar, albeit less marked, changes in neuroendocrine activity and anterior hippocampal function, but not reduced anterior hippocampal volume. Indeed, reduced anterior hippocampal volume is seen in patients with normal water balance (nonpolydipsic normonatremic schizophrenics: NNS) whose neuroendocrine activity and anterior hippocampal function differ markedly from those with polydipsia. In an effort to reconcile these findings we measured hippocampal, amygdala and 3rd ventricle shapes in 26 schizophrenic patients (10 PNS, 7 PHS, 9 NNS) and 12 healthy controls matched for age and gender. Bilateral inward deformations were localized to the anterior lateral hippocampal surface (part of a neurocircuit which modulates neuroendocrine responses to psychological stimuli) in PHS and to a lesser extent in PNS, while deformations in NNS were restricted to the medial surface. Proportional deformations of the right medial amygdala, a key segment of this neurocircuit, were seen in both polydipsic groups, and correlated with the volume of the 3rd ventricle, which lies adjacent to the neuroendocrine nuclei. Finally, these structural findings were most marked in those with impaired hippocampal-mediated stress responses. These results reconcile previously conflicting data, and support the view that anterior lateral hippocampal pathology disrupts neuroendocrine function in polydipsic patients with and without hyponatremia. The relationship of these findings to the underlying mental illness remains to be established. PMID:21093493

  1. Radiotherapy for Pancreatic Neuroendocrine Tumors

    SciTech Connect

    Contessa, Joseph N.; Griffith, Kent A.; Wolff, Elizabeth; Ensminger, William; Zalupski, Mark; Ben-Josef, Edgar

    2009-11-15

    Purpose: Pancreatic neuroendocrine tumors (PNTs) are rare malignant neoplasms considered to be resistant to radiotherapy (RT), although data on efficacy are scarce. We reviewed our institutional experience to further delineate the role of RT for patients with PNTs. Methods and Materials: Between 1986 and 2006, 36 patients with PNTs were treated with RT to 49 sites. Of these 36 patients, 23 had radiographic follow-up data, which were used to determine the tumor response rate and freedom from local progression. Long-term toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: The overall response rate to RT was 39% (13% complete response, 26% partial response, 56% stable disease, and 4% progressive disease). A significant difference in the freedom from local progression between the groups receiving either greater than or less than the median 2 Gy/fraction biologically equivalent dose of 49.6 Gy was found, with all radiographic progression occurring in patients who had received <=32 Gy. The actuarial 3-year local freedom from progression rate was 49%. Palliation was achieved in 90% of patients, with either improvement or resolution of symptoms after RT. Of 35 patients, 33 had metastatic disease at their referral for RT, and the median overall survival for this patient population was 2 years. Three long-term Grade 3 or greater toxicities were recorded. Conclusion: RT is an effective modality for achieving local control in patients with PNTs. RT produces high rates of symptomatic palliation and freedom from local progression. Prospective trials of radiotherapy for PNTs are warranted.

  2. Optimizacion of Babesia bovis transfection methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tick borne Babesia parasites remain an important limitation for development of cattle industries worldwide. A stable transfection of Babesia bovis will be useful for functional analysis of the recently sequenced B. bovis genome and to design improved methods to control Babesia infections. In thi...

  3. Neuroendocrine Disruption: More than Hormones are Upset

    PubMed Central

    Waye, Andrew; Trudeau, Vance L.

    2011-01-01

    Only a small proportion of the published research on endocrine-disrupting chemicals (EDC) directly examined effects on neuroendocrine processes. There is an expanding body of evidence that anthropogenic chemicals exert effects on neuroendocrine systems and that these changes might impact peripheral organ systems and physiological processes. Neuroendocrine disruption extends the concept of endocrine disruption to include the full breadth of integrative physiology (i.e., more than hormones are upset). Pollutants may also disrupt numerous other neurochemical pathways to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. Several examples are presented in this review, from both vertebrates and invertebrates, illustrating that diverse environmental pollutants including pharmaceuticals, organochlorine pesticides, and industrial contaminants have the potential to disrupt neuroendocrine control mechanisms. While most investigations on EDC are carried out with vertebrate models, an attempt is also made to highlight the importance of research on invertebrate neuroendocrine disruption. The neurophysiology of many invertebrates is well described and many of their neurotransmitters are similar or identical to those in vertebrates; therefore, lessons learned from one group of organisms may help us understand potential adverse effects in others. This review argues for the adoption of systems biology and integrative physiology to address the effects of EDC. Effects of pulp and paper mill effluents on fish reproduction are a good example of where relatively narrow hypothesis testing strategies (e.g., whether or not pollutants are sex steroid mimics) have only partially solved a major problem in environmental biology. It is clear that a global, integrative physiological approach, including improved understanding of neuroendocrine control mechanisms, is warranted to fully understand the impacts of pulp and paper mill effluents

  4. Neuroendocrine tumors: common presentations of uncommon diseases.

    PubMed

    Kirkwood, K S; Debas, H T

    1995-12-01

    In recent decades, isolation of the peptides secreted by gastrointestinal neuroendocrine tumors has greatly advanced our understanding of the pathophysiology of the syndromes resulting from over-production of these biologically active compounds. Early detection of these lesions permits localization and surgical extirpation prior to the development of mestastatic disease. In 1995, early detection of gastrointestinal neuroendocrine tumors hinges on an appropriate index of suspicion on the part of the primary care physician. The prompt recognition of the typical clinical constellations of symptoms associated with these tumors is essential to their timely diagnosis and management. PMID:8789136

  5. Gastrointestinal stromal tumour.

    PubMed

    Joensuu, Heikki; Hohenberger, Peter; Corless, Christopher L

    2013-09-14

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine and rarely elsewhere in the abdomen. They can occur at any age, the median age being 60-65 years, and typically cause bleeding, anaemia, and pain. GISTs have variable malignant potential, ranging from small lesions with a benign behaviour to fatal sarcomas. Most tumours stain positively for the mast/stem cell growth factor receptor KIT and anoctamin 1 and harbour a kinase-activating mutation in either KIT or PDGFRA. Tumours without such mutations could have alterations in genes of the succinate dehydrogenase complex or in BRAF, or rarely RAS family genes. About 60% of patients are cured by surgery. Adjuvant treatment with imatinib is recommended for patients with a substantial risk of recurrence, if the tumour has an imatinib-sensitive mutation. Tyrosine kinase inhibitors substantially improve survival in advanced disease, but secondary drug resistance is common. PMID:23623056

  6. Transport processes in tumours.

    PubMed

    Quastel, J H

    1965-12-01

    The characteristic features of transport systems controlling influx into tumour cells of nutrients and other chemicals are briefly described. Two notable features of transport of amino acids into tumour cells have been observed: extensive accumulation against a concentration gradient and equal accumulations, whether conditions are aerobic or anaerobic, provided glucose is present. This combination of features has not been observed in the majority of normal mammalian tissues so far examined. Important for considerations of chemotherapy is the ability of tumour transport carriers to transfer substances related in structure to amino acids and other nutrients. Amino acid analogues, for example, can either block transport of natural amino acids or can be transported into the cell where they may interfere with various aspects of amino acid metabolism. The study of transport carriers is essential for an understanding of tumour-host relationships and for considerations of chemotherapy. PMID:5842595

  7. Breast tumour angiogenesis

    PubMed Central

    Fox, Stephen B; Generali, Daniele G; Harris, Adrian L

    2007-01-01

    The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized. PMID:18190723

  8. Testicular germ cell tumours.

    PubMed

    Rajpert-De Meyts, Ewa; McGlynn, Katherine A; Okamoto, Keisei; Jewett, Michael A S; Bokemeyer, Carsten

    2016-04-23

    Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors. PMID:26651223

  9. Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma.

    PubMed

    Shah, Ketan; Perez-Ordóñez, Bayardo

    2016-03-01

    Neuroendocrine neoplasms (NENs) can occur in organs or tissues that do not contain neuroendocrine cells normally and do not necessarily imply embryologic derivation from the neuroectoderm; but rather reflect a shared phenotype characterized by the expression of multiple genes encoding both endocrine and neuronal features. NENs are rare in the sinonasal tract and are subdivided into epithelial and neural subtypes based on the presence of keratins or neurofilaments, respectively. Although relatively rare, neuroendocrine carcinomas (NECs) and olfactory neuroblastoma (ONB) are the most common neuroendocrine neoplasms of the sinonasal tract. The focus of this review is to highlight recent developments in the pathology of sinonasal NECs and ONB in light of the upcoming update of the World Health Organization (WHO) 2005 classification of tumors of the head and neck. PMID:26830400

  10. Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

    PubMed

    Aktas, G E; Soyluoglu Demir, S; Sarikaya, A

    2016-01-01

    The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma. PMID:26522002

  11. Neuroendocrine host factors and inflammatory disease susceptibility.

    PubMed Central

    Ligier, S; Sternberg, E M

    1999-01-01

    The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. PMID:10502534

  12. Skin manifestations of endocrine and neuroendocrine tumors.

    PubMed

    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. PMID:27178685

  13. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    PubMed Central

    Rinke, Anja; Michl, Patrick; Gress, Thomas

    2012-01-01

    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. PMID:24213230

  14. NEUROENDOCRINE AND REPRODUCTIVE EFFECTS OF PESTICIDES

    EPA Science Inventory

    Neuroendocrine and Reproductive Effects of Pesticides

    1Stoker, TE, Goldman 2, JM and Cooper 2, RL.

    1Gamete and Early Embryogenesis Biology Branch and 2 Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laborat...

  15. Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

    PubMed Central

    Daubenbüchel, Anna M. M.; Müller, Hermann L.

    2015-01-01

    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. PMID:26239246

  16. Lipid-based Transfection Reagents Exhibit Cryo-induced Increase in Transfection Efficiency.

    PubMed

    Sork, Helena; Nordin, Joel Z; Turunen, Janne J; Wiklander, Oscar Pb; Bestas, Burcu; Zaghloul, Eman M; Margus, Helerin; Padari, Kärt; Duru, Adil D; Corso, Giulia; Bost, Jeremy; Vader, Pieter; Pooga, Margus; Smith, Ci Edvard; Wood, Matthew Ja; Schiffelers, Raymond M; Hällbrink, Mattias; Andaloussi, Samir El

    2016-01-01

    The advantages of lipid-based transfection reagents have permitted their widespread use in molecular biology and gene therapy. This study outlines the effect of cryo-manipulation of a cationic lipid-based formulation, Lipofectamine 2000, which, after being frozen and thawed, showed orders of magnitude higher plasmid delivery efficiency throughout eight different cell lines, without compromising cell viability. Increased transfection efficiency with the freeze-thawed reagent was also seen with 2'-O-methyl phosphorothioate oligonucleotide delivery and in a splice-correction assay. Most importantly, a log-scale improvement in gene delivery using the freeze-thawed reagent was seen in vivo. Using three different methods, we detected considerable differences in the polydispersity of the different nucleic acid complexes as well as observed a clear difference in their surface spreading and sedimentation, with the freeze-thawed ones displaying substantially higher rate of dispersion and deposition on the glass surface. This hitherto overlooked elevated potency of the freeze-thawed reagent facilitates the targeting of hard-to-transfect cells, accomplishes higher transfection rates, and decreases the overall amount of reagent needed for delivery. Additionally, as we also saw a slight increase in plasmid delivery using other freeze-thawed transfection reagents, we postulate that freeze-thawing might prove to be useful for an even wider variety of transfection reagents. PMID:27111416

  17. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

    The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient. PMID:8678441

  18. Toward Contactless Biology: Acoustophoretic DNA Transfection

    NASA Astrophysics Data System (ADS)

    Vasileiou, Thomas; Foresti, Daniele; Bayram, Adem; Poulikakos, Dimos; Ferrari, Aldo

    2016-02-01

    Acoustophoresis revolutionized the field of container-less manipulation of liquids and solids by enabling mixing procedures which avoid contamination and loss of reagents due to the contact with the support. While its applications to chemistry and engineering are straightforward, additional developments are needed to obtain reliable biological protocols in a contactless environment. Here, we provide a first, fundamental step towards biological reactions in air by demonstrating the acoustophoretic DNA transfection of mammalian cells. We developed an original acoustophoretic design capable of levitating, moving and mixing biological suspensions of living mammalians cells and of DNA plasmids. The precise and sequential delivery of the mixed solutions into tissue culture plates is actuated by a novel mechanism based on the controlled actuation of the acoustophoretic force. The viability of the contactless procedure is tested using a cellular model sensitive to small perturbation of neuronal differentiation pathways. Additionally, the efficiency of the transfection procedure is compared to standard, container-based methods for both single and double DNA transfection and for different cell types including adherent growing HeLa cancer cells, and low adhesion neuron-like PC12 cells. In all, this work provides a proof of principle which paves the way to the development of high-throughput acoustophoretic biological reactors.

  19. Toward Contactless Biology: Acoustophoretic DNA Transfection

    PubMed Central

    Vasileiou, Thomas; Foresti, Daniele; Bayram, Adem; Poulikakos, Dimos; Ferrari, Aldo

    2016-01-01

    Acoustophoresis revolutionized the field of container-less manipulation of liquids and solids by enabling mixing procedures which avoid contamination and loss of reagents due to the contact with the support. While its applications to chemistry and engineering are straightforward, additional developments are needed to obtain reliable biological protocols in a contactless environment. Here, we provide a first, fundamental step towards biological reactions in air by demonstrating the acoustophoretic DNA transfection of mammalian cells. We developed an original acoustophoretic design capable of levitating, moving and mixing biological suspensions of living mammalians cells and of DNA plasmids. The precise and sequential delivery of the mixed solutions into tissue culture plates is actuated by a novel mechanism based on the controlled actuation of the acoustophoretic force. The viability of the contactless procedure is tested using a cellular model sensitive to small perturbation of neuronal differentiation pathways. Additionally, the efficiency of the transfection procedure is compared to standard, container-based methods for both single and double DNA transfection and for different cell types including adherent growing HeLa cancer cells, and low adhesion neuron-like PC12 cells. In all, this work provides a proof of principle which paves the way to the development of high-throughput acoustophoretic biological reactors. PMID:26828312

  20. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  1. Tumours of the thymus

    PubMed Central

    Sellors, T. Holmes; Thackray, A. C.; Thomson, A. D.

    1967-01-01

    Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed. Images PMID:6033387

  2. Radiotherapy for ocular tumours.

    PubMed

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-02-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  3. Radiotherapy for ocular tumours

    PubMed Central

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-01-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25–30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  4. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  5. Immunology of naturally transmissible tumours.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  6. Glyoxalase I in detoxification: studies using a glyoxalase I transfectant cell line.

    PubMed Central

    Ranganathan, S; Walsh, E S; Tew, K D

    1995-01-01

    The glyoxalase system (glyoxalase I, glyoxalase II and GSH as cofactor) is involved in the detoxification of methylglyoxal (a byproduct of the glycolytic pathway) and other alpha-oxoaldehydes. We have transfected a 622 bp cDNA encoding human glyoxalase I into murine NIH3T3 cells. The recipient cells were shown to express elevated transcript and protein levels and a 10-fold increase in glyoxalase I enzyme activity. This was accompanied by an increased tolerance for exogenous methylglyoxal and enhanced resistance to the cytotoxic effects of two glyoxalase I inhibitors (s-p-bromobenzylglutathione diethyl ester and s-p-bromobenzylglutathione dicyclopentyl ester), a glutathione analogue [gamma-glutamyl-(S)-(benzyl)cysteinyl-(R)-(-)-phenylglycine diethyl ester] and the anti-cancer drugs mitomycin C and adriamycin. Steady-state levels of GSH were significantly lower in the transfected cells, perhaps reflecting increased flux as a consequence of elevated glyoxalase activity. This decrease did not alter the sensitivity to the alkylating agent chlorambucil. Although transfection did not affect the growth or doubling time of the NIH3T3 cells, analysis of glyoxalase I activity showed a consistent increase in tumour tissue when compared with pair-matched controls. Thus increased glyoxalase I is associated with the malignant phenotype and may also contribute to protection against the cytotoxicity of certain anti-cancer drugs. Images Figure 1 PMID:7619046

  7. Infection, transfection, and co-transfection of baculoviruses by microprojectile bombardment of larvae.

    PubMed

    Obregón-Barboza, Verónica; Del Rincón-Castro, Ma Cristina; Cabrera-Ponce, José L; Ibarra, Jorge E

    2007-03-01

    The use of baculoviruses as expression vectors for heterologous proteins has been practically limited to the use of the Autographa californica multiple nucleopolyhedrovirus (AcMNPV). In this work, infection, transfection and co-transfection events with the baculoviruses AcMNPV and Trichoplusia ni granulovirus (TnGV) were accomplished by bombardment of T. ni first-instar larvae with microprojectiles coated with virions, viral DNA, and viral DNA and a transfer vector, respectively. A series of shooting conditions were tested until positive results were obtained. The use of 1.6 microm gold particles at 900 psi shooting pressure, 400 Torr vacuum, 7 cm distance to target, on sets of 20 first-instar larvae held in a 16 mm diameter container, proved to be the best shooting conditions. Typical infection symptoms were shown by larvae when shot with viruses or viral DNA from AcMNPV or TnGV. Co-transfected recombinant AcMNPV and TnGV were identified by the formation of occlusion bodies and GFP, respectively, in bombarded larvae. This technique opens a wide range of possibilities, not only to use an extensive number of baculoviruses as expression vectors for heterologous proteins, but also be used to infect, transfect or co-transfect a wide variety of viruses into animal cells. PMID:17184851

  8. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  9. Mixed acinar-neuroendocrine carcinoma of the pancreas with neuroendocrine predominance.

    PubMed

    Ogbonna, Onyekachi Henry; Garcon, Marie Carmel; Syrigos, Kostas N; Saif, Muhammad Wasif

    2013-01-01

    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. PMID:24348574

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

    PubMed Central

    Ogbonna, Onyekachi Henry; Syrigos, Kostas N.; Saif, Muhammad Wasif

    2013-01-01

    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. PMID:24348574

  11. [Update of pathological diagnosis of pulmonary neuroendocrine tumor].

    PubMed

    Xiaodong, Teng; Ming, Zhao; Maode, Lai

    2016-05-25

    Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis. PMID:27045239

  12. The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

    PubMed Central

    Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

    2015-01-01

    Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

  13. Network of immune-neuroendocrine interactions.

    PubMed Central

    Besedovsky, H; Sorkin, E

    1977-01-01

    In order to bring the self-regulated immune system into conformity with other body systems its functioning within the context of an immune-neuroendocrine network is proposed. This hypothesis is based on the existence of afferent--efferent pathways between immune and neuroendocrine structures. Major endocrine responses occur as a consequence of antigenic stimulation and changes in the electrical activity of the hypothalamus also take place; both of these alterations are temporally related to the immune response itself. This endocrine response has meaningful implications for immunoregulation and for immunospecificity. During ontogeny, there is also evidence for the operations of a complex network between the endocrine and immune system, a bidirectional interrelationship that may well affect each developmental stage of both functions. As sequels the functioning of the immune system and the outcome of this interrelation could be decisive in lymphoid cell homeostasis, self-tolerance, and could also have significant implications for pathology. PMID:849642

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

    PubMed Central

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

    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, locoregional 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. PMID:23237225

  15. Neuroendocrine Causes of Amenorrhea—An Update

    PubMed Central

    Fourman, Lindsay T.

    2015-01-01

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

  16. Gastroenteropancreatic neuroendocrine tumors: diagnosis and treatment

    PubMed Central

    Díez, Marc; Teulé, Alexandre; Salazar, Ramon

    2013-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare and complex neoplasms that present many clinical challenges. Most GEP-NETs are sporadic, but they can be multiple and a component of a familial syndrome. Assessment of the location and extent of GEP-NETs is crucial for management and a number of novel imaging modalities are under evaluation with the principal goal of increasing sensitivity for the detection of micro-metastases while retaining specificity. The appropriate diagnosis and treatment of neuroendocrine tumors often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Management strategies include surgery, radiological intervention, cytotoxic chemotherapies, somatostatin analogs and novel biological agents such as sunitinib and everolimus. Other biological agents, new chemoteraphy regimens and somatostatin-tagged radionuclide therapies are also under investigation. In spite of this, comparison between therapeutic modalities is currently difficult. Further studies are warranted to individualize and optimize the diagnosis and treatment of these tumors. PMID:24714698

  17. Canine neuroendocrine carcinoma. A tumor resembling histiocytoma.

    PubMed

    Nickoloff, B J; Hill, J; Weiss, L M

    1985-12-01

    The clinical and light- and electron microscopic features of 20 cases of canine neuroendocrine carcinoma, initially classified as atypical histiocytomas, are reported. The locally expansile well-circumscribed dermal tumor nodules were composed of solid masses of cells with high mitotic index and multinucleation, arranged in a trabecular pattern with prominent fibrovascular connective tissue stroma rich in reticulin fibers that outlined compact cell nests. Ultrastructural studies revealed evenly dispersed chromatin, focally indented nuclei and abundant cytoplasm with perinuclear filaments, membrane-bound dense core granules, and prominent interdigitating plasma membrane projections with primitive intercellular junctions. Clinical and pathological comparisons between canine neuroendocrine carcinoma, canine histiocytomas, and human Merkel cell neoplasms are discussed. PMID:4091229

  18. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  19. A General RNA Motif for Cellular Transfection

    PubMed Central

    Magalhães, Maria LB; Byrom, Michelle; Yan, Amy; Kelly, Linsley; Li, Na; Furtado, Raquel; Palliser, Deborah; Ellington, Andrew D; Levy, Matthew

    2012-01-01

    We have developed a selection scheme to generate nucleic acid sequences that recognize and directly internalize into mammalian cells without the aid of conventional delivery methods. To demonstrate the generality of the technology, two independent selections with different starting pools were performed against distinct target cells. Each selection yielded a single highly functional sequence, both of which folded into a common core structure. This internalization signal can be adapted for use as a general purpose reagent for transfection into a wide variety of cell types including primary cells. PMID:22233578

  20. Biochemical diagnosis of neuroendocrine GEP tumor.

    PubMed Central

    Oberg, K.

    1997-01-01

    Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor

  1. Neuroendocrine carcinoma of the prostate gland

    PubMed Central

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

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease. PMID:26722176

  2. Neuroendocrine regulation of appetitive ingestive behavior

    PubMed Central

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

    2013-01-01

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

  3. Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2014-11-14

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Neuroendocrine Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  4. Primary Neuroendocrine Tumors of the Ureter: A Short Review.

    PubMed

    Acosta, Andres M; Kajdacsy-Balla, Andre

    2016-07-01

    Neuroendocrine tumors represent 0.05% of urinary tract malignancies, and most originate in the bladder. Their pathogenesis is debated, since ureters are thought to lack neuroendocrine cells. Morphologically, most ureteral neuroendocrine tumors demonstrate the typical small cell neuroendocrine appearance, are immunohistochemically positive for synaptophysin/chromogranin A/CD56, and show electron-dense granules by electron microscopy. Clinical presentation is similar to that of other more common ureteral neoplasms. Prognosis is usually dismal, but a multimodal treatment approach including platinum-based adjuvant or neoadjuvant chemotherapy seems to be beneficial. PMID:27362572

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

    PubMed

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

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies. PMID:27035909

  6. Management of early gastrointestinal neuroendocrine neoplasms

    PubMed Central

    Scherübl, Hans; Jensen, Robert T; Cadiot, Guillaume; Stölzel, Ulrich; Klöppel, Günter

    2011-01-01

    Neuroendocrine neoplasms (NENs) of the stomach, duodenum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered “early” tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better general availability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient. PMID:21860682

  7. Surgical management of pancreatic neuroendocrine tumors.

    PubMed

    Kimura, Wataru; Tezuka, Koji; Hirai, Ichiro

    2011-10-01

    This study outlines the surgical management and clinicopathological findings of pancreatic neuroendocrine tumors (P-NETs). There are various surgical options, such as enucleation of the tumor, spleen-preserving distal pancreatectomy, distal pancreatectomy with splenectomy, pancreatoduodenectomy, and duodenum-preserving pancreas head resection. Lymph node dissection is performed for malignant cases. New guidelines and classifications have been proposed and are now being used in clinical practice. However, there are still no clear indications for organ-preserving pancreatic resection or lymph node dissection. Hepatectomy is the first choice for liver metastases of well-differentiated neuroendocrine carcinoma without extrahepatic metastases. On the other hand, cisplatin-based combination therapy is performed as first-line chemotherapy for metastatic poorly differentiated neuroendocrine carcinoma. Other treatment options are radiofrequency ablation, transarterial chemoembolization/embolization, and liver transplantation. Systematic chemotherapy and biotherapy, such as that with somatostatin analogue and interferon-α, are used for recurrence after surgery. The precise surgical techniques for enucleation of the tumor and spleen-preserving distal pancreatectomy are described. PMID:21922354

  8. GEP- NETS UPDATE: Genetics of neuroendocrine tumors.

    PubMed

    Crona, Joakim; Skogseid, Britt

    2016-06-01

    Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, arising from neuroendocrine cells that are dispersed throughout the body. Around 20% of NETs occur in the context of a genetic syndrome. Today there are at least ten recognized NET syndromes. This includes the classical syndromes: multiple endocrine neoplasias types 1 and 2, and von Hippel-Lindau and neurofibromatosis type 1. Additional susceptibility genes associated with a smaller fraction of NETs have also been identified. Recognizing genetic susceptibility has proved essential both to provide genetic counseling and to give the best preventive care. In this review we will also discuss the knowledge of somatic genetic alterations in NETs. At least 24 genes have been implicated as drivers of neuroendocrine tumorigenesis, and the overall rates of genomic instability are relatively low. Genetic intra-tumoral, as well as inter-tumoral heterogeneity in the same patient, have also been identified. Together these data point towards the common pathways in NET evolution, separating early from late disease drivers. Although knowledge of specific mutations in NETs has limited impact on actual patient management, we predict that in the near future genomic profiling of tumors will be included in the clinical arsenal for diagnostics, prognostics and therapeutic decisions. PMID:27165966

  9. Stress induced neuroendocrine-immune plasticity

    PubMed Central

    Liezmann, Christiane; Stock, Daniel; Peters, Eva M. J.

    2012-01-01

    Research over the past decade has revealed close interaction between the nervous and immune systems in regulation of peripheral inflammation linking psychosocial stress with chronic somatic disease and aging. Moreover emerging data suggests that chronic inflammations lead to a pro-inflammatory status underlying premature aging called inflammaging. In this context, the spleen can be seen as a switch board monitoring peripherally derived neuroendocrine-immune mediators in the blood and keeping up a close communication with the central stress response via its mainly sympathetic innervation. The effect aims at balanced and well-timed stress axis activation and immune adaptation in acute peripheral inflammatory events. Constant adjustment to the needs generated by environmental and endogenous challenges is provided by neuroendocrine-immune plasticity. However, maladaptive plasticity induced e.g., by chronic stress-axis activation and excessive non-neuronal derived neuroendocrine mediators may be at the heart of the observed stress sensitivity promote inflammaging under chronic inflammatory conditions. We here review the role of neurotransmitters, neuropeptides and neurotrophins as stress mediators modulating the immune response in the spleen and their potential role in inflammaging. PMID:23467333

  10. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

    Uterine fatty tumours (UFT) are uncommon and have received little attention in the English literature. They have aroused interest as a consequence of occasional diagnostic confusion with sarcomas and the continuing unresolved dispute as to their histogenesis. Three cases of UFT are described and the pathological features of note discussed. The viewpoint that these tumours are hamartomas/choristomas is rejected. UFT most probably represent tumour metaplasia within a leiomyoma. There is no uniform accepted nomenclature for such tumours and it is suggested that they be designated "uterine fatty tumours" and subdivided into "lipoma" and "mixed lipoma/leiomyoma" (synonym lipoleiomyoma). Images PMID:7174848

  11. Glomus tumour of the stomach.

    PubMed

    Troller, Rebekka; Soll, Christopher; Breitenstein, Stefan

    2016-01-01

    Glomus tumours are benign tumours typically arising from the glomus bodies and primarily found under the fingernails or toenails. These rare neoplasms account for <2% of all soft tissue tumours and are generally not found in the gastrointestinal tract. We report a case of a 40-year-old man presenting with recurrent epigastric pain and pyrosis. Endoscopy revealed a solitary tumour in the antrum of the stomach. Fine-needle aspiration biopsy was suspicious for a gastrointestinal stroma tumour. After CT indicated the resectability of the tumour, showing neither lymphatic nor distant metastases, a laparoscopic-assisted gastric wedge resection was performed. Surprisingly, histology revealed a glomus tumour of the stomach. PMID:27343282

  12. Tumours of the kidney

    PubMed Central

    Nielsen, Svend W.; Mackey, L. J.; Misdorp, W.

    1976-01-01

    The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. ImagesFig. 5,6Fig. 7Fig. 8Fig. 1,2Fig. 3,4Fig. 16,17,18,19Fig. 9,10Fig. 11Fig. 12Fig. 13Fig. 14,15 PMID:1086154

  13. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  14. Gene transfection by echo contrast agent microbubbles

    NASA Astrophysics Data System (ADS)

    Tachibana, Katsuro

    2002-11-01

    In vitro and in vivo experiments have demonstrated that various echo contrast agent microbubbles can be intentionally ruptured by diagnostic and therapeutic ultrasound. Violent microstreaming are produced during microbubble collapse. Researchers have hypothesized that these microjets or microstreaming could be applied to promote diffusion of drugs into various tissues and lesions. The most exciting application of this method is probably delivery of genes into cells. As various genes are currently under investigation for the purpose of treating diseases, ultrasound and microbubbles may be used as a modality to promote better outcome for gene therapy. Recent studies have shown that different gases contained within the bubbles greatly influence the degree of gene transfection. Also, the outer layer of the microbubbles can be custom-made for binding to target tissue. Recent advance on this topic will be discussed.

  15. Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases

    PubMed Central

    Cansız Ersöz, Cevriye; Cangır, Ayten Kayı; Dizbay Sak, Serpil

    2016-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors. PMID:27293939

  16. Plasma-mediated transfection of RPE

    NASA Astrophysics Data System (ADS)

    Palanker, D.; Chalberg, T.; Vankov, A.; Huie, P.; Molnar, F. E.; Butterwick, A.; Calos, M.; Marmor, M.; Blumenkranz, M. S.

    2006-02-01

    A major obstacle in applying gene therapy to clinical practice is the lack of efficient and safe gene delivery techniques. Viral delivery has encountered a number of serious problems including immunological reactions and malignancy. Non-viral delivery methods (liposomes, sonoporation and electroporation) have either low efficiency in-vivo or produce severe collateral damage to ocular tissues. We discovered that tensile stress greatly increases the susceptibility of cellular membranes to electroporation. For synchronous application of electric field and mechanical stress, both are generated by the electric discharge itself. A pressure wave is produced by rapid vaporization of the medium. To prevent termination of electric current by the vapor cavity it is ionized thus restoring its electric conductivity. For in-vivo experiments with rabbits a plasmid DNA was injected into the subretinal space, and RPE was treated trans-sclerally with an array of microelectodes placed outside the eye. Application of 250-300V and 100-200 μs biphasic pulses via a microelectrode array resulted in efficient transfection of RPE without visible damage to the retina. Gene expression was quantified and monitored using bioluminescence (luciferase) and fluorescence (GFP) imaging. Transfection efficiency of RPE with this new technique exceeded that of standard electroporation by a factor 10,000. Safe and effective non-viral DNA delivery to the mammalian retina may help to materialize the enormous potential of the ocular gene therapy. Future experiments will focus on continued characterization of the safety and efficacy of this method and evaluation of long-term transgene expression in the presence of phiC31 integrase.

  17. Biophysical models of tumour growth

    NASA Astrophysics Data System (ADS)

    Tracqui, P.

    2009-05-01

    Tumour growth is a multifactorial process, which has stimulated in recent decades the development of numerous models trying to figure out the mechanisms controlling solid tumours morphogenesis. While the earliest models were focusing on cell proliferation kinetics, modulated by the availability of supplied nutrients, new modelling approaches emphasize the crucial role of several biophysical processes, including local matrix remodelling, active cell migration and traction, and reshaping of host tissue vasculature. After a brief presentation of this experimental background, this review will outline a number of representative models describing, at different scales, the growth of avascular and vascularized tumours. Special attention will be paid to the formulation of tumour-host tissue interactions that selectively drive changes in tumour size and morphology, and which are notably mediated by the mechanical status and elasticity of the tumour microenvironment. Emergence of invasive behaviour through growth instabilities at the tumour-host interface will be presented considering both reaction-diffusion and mechano-cellular models. In the latter part of the review, patient-oriented implications of tumour growth modelling are outlined in the context of brain tumours. Some conceptual views of the adaptive strategies and selective barriers that govern tumour evolution are presented in conclusion as potential guidelines for the development of future models.

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

    PubMed Central

    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

  19. Single cell transfection using plasmid decorated AFM probes

    SciTech Connect

    Cuerrier, Charles M.; Lebel, Rejean; Grandbois, Michel . E-mail: michel.grandbois@usherbrooke.ca

    2007-04-13

    Eukaryotic cells were individually transfected using commercially available atomic force microscope tips decorated with plasmidic DNA encoding for the fluorescent protein EGFP. In a typical transfection attempt, the tip is forcibly incorporated into the cell thus allowing for the transfer of the genetic material through the cell membrane. A sharp discontinuity, corresponding to the passage of the tip through the cell membrane can be easily detected when monitoring the cellular deformation as a function of the applied force. In order for the transfection to be successful, the tip must reversibly penetrates the membrane without causing disturbance or damage to the cell. Transfection success rate (30%), cell survival, and growth are confirmed by epifluorescence microscopy. This technique provides an alternative tool to the transfection toolbox, allowing the transfection of specific individual cells with minimal disturbance.

  20. Neuroendocrine carcinoma of the larynx with metastasis to the eyelid.

    PubMed

    Assi, Hussein A; Patel, Raina; Mehdi, Syed

    2015-10-01

    Neuroendocrine tumors are a rare type of neoplasms that comprise only 0.5% of all malignancies.¹ They usually arise from the gastrointestinal tract and the lung.¹,² Neuroendocrine carcinoma of the head and neck is a relatively rare malignancy described in the literature. The larynx is the most commonly affected region of the head and neck.³,⁴ Nevertheless, small-cell carcinoma comprises only 0.5% of all laryngeal cancers.⁵ Neuroendocrine carcinoma of the larynx carries variable prognosis depending on the histological subtype.⁶ Typical carcinoid rarely metastasizes, but atypical carcinoid and small-cell carcinoma have high rates of metastasis, usually in the lung and liver.² Cutaneous metastasis from neuroendocrine carcinoma is an extremely rare entity, with only few cases reported in the English literature.⁷,⁸ We report the case of an elderly man with recurrent laryngeal neuroendocrine carcinoma with metastasis to the eyelid. PMID:26862914

  1. Recurrent gastric neuroendocrine tumors treated with total gastrectomy

    PubMed Central

    Jung, Myounghwa; Kim, Jung-Wook; Jang, Jae-Young; Chang, Young Woon; Park, Sun Hee; Kim, Yong Ho; Kim, Youn Wha

    2015-01-01

    Gastric neuroendocrine tumors are rare; however, the incidence has recently increased due to the increasing use of upper endoscopy. Neuroendocrine tumors arise from the excess proliferation of enterochromaffin-like (ECL) cells. The proliferative changes of enterochromaffin cells evolve through a hyperplasia-dysplasia-neoplasia sequence that is believed to underlie the pathogenesis of gastric neuroendocrine tumors. Endoscopic resection is recommended as the initial treatment if the tumor is not in an advanced stage. However, there is no definite guideline for the treatment of recurrent gastric neuroendocrine tumors following endoscopic resection. Here, we report a rare case of gastric neuroendocrine tumors in a 56-year-old male who experienced two recurrences within 11 years after endoscopic resection. The patient finally underwent a total gastrectomy. The pathological features of the resected stomach exhibited the full hyperplasia-dysplasia-neoplasia sequence of the ECL cells in a single specimen. PMID:26675502

  2. Molecular aspects of prostate cancer with neuroendocrine differentiation

    PubMed Central

    Li, Qi; Zhang, Connie S.

    2016-01-01

    Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy (ADT) and generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine cells, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate cells. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review. PMID:27041934

  3. Neuroendocrine differentiation: The mysterious fellow of colorectal cancer

    PubMed Central

    Kleist, Britta; Poetsch, Micaela

    2015-01-01

    Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer. PMID:26556999

  4. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

    Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria

    2014-01-01

    Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours. PMID:25654053

  5. Mammalian cell transfection: the present and the future

    PubMed Central

    Kim, Tae Kyung

    2010-01-01

    Transfection is a powerful analytical tool enabling study of the function of genes and gene products in cells. The transfection methods are broadly classified into three groups; biological, chemical, and physical. These methods have advanced to make it possible to deliver nucleic acids to specific subcellular regions of cells by use of a precisely controlled laser-microcope system. The combination of point-directed transfection and mRNA transfection is a new way of studying the function of genes and gene products. However, each method has its own advantages and disadvantages so the optimum method depends on experimental design and objective. PMID:20549496

  6. Optimization of Transfection Conditions for siRNA Screening.

    PubMed

    Montoya, Justin J; Azorsa, David O

    2016-01-01

    RNAi screening of mammalian cells is often performed using siRNAs and cationic lipids as transfection reagents. Efficiency of transfection depends on growth characteristics of the cells and the cationic lipid used. With a large selection of cationic lipids available, it can often be difficult to select the optimal lipid and lipid:siRNA (vol:wt) ratio. Here, we describe the process of optimizing siRNA transfection conditions for efficient reverse transfection of mammalian cells using specific positive and negative siRNA controls. PMID:27581281

  7. Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines

    PubMed Central

    Tonetti, D A; Chisamore, M J; Grdina, W; Schurz, H; Jordan, V C

    2000-01-01

    An inverse relationship between protein kinase C (PKC) activity and oestrogen receptor (ER) expression in human breast cell lines and tumours has been firmly established over the past 10 years. To determine whether specific alterations in PKC expression accompany hormone-independence, we examined the expression of PKC isozymes in the hormone-independent human breast cancer cell clones MCF-7 5C and T47D:C42 compared with their hormone-dependent counterparts, MCF-7 A4, MCF-7 WS8 and T47D:A18 respectively. Both hormone-independent cell clones exhibit elevated PKCα expression and increased basal AP-1 activity compared with the hormone-dependent cell clones. To determine whether PKCα overexpression is sufficient to mediate the hormone-independent phenotype, we stably transfected an expression plasmid containing PKCα cDNA to the T47D:A18 and MCF-7 A4 cell lines. This is the first report of PKCα transfection in T47D cells. In contrast to MCF-7 cells, T47D has the propensity to lose the ER and more readily forms tamoxifen-stimulated tumours in athymic mice. We find that in T47D:A18/PKCα clones, there is concomitant up-regulation of PKC βI and δ, whereas in the MCF-7 A4/PKCα transfectants PKC ɛ is up-regulated. In T47D:A18, but not in MCF-7 A4, PKCα stable transfection is accompanied by down-regulation of ER function whilst basal AP-1 activity is elevated. Our results suggest PKCα overexpression may play a role in growth signalling during the shift from hormone dependent to hormone-independent breast cancers. © 2000 Cancer Research Campaign PMID:10952784

  8. The role of the ras oncogene in the formation of tumours.

    PubMed

    Gilbert, P X; Harris, H

    1988-07-01

    A c-Ha-ras 1 oncogene, cloned from the EJ human bladder carcinoma cell line, was inserted into a shuttle vector carrying the selectable marker gene gpt that encodes the enzyme xanthine-guanine phosphoribosyl transferase. This construct, pSV2gptEJ, was transfected into NIH 3T3 cells by the calcium phosphate precipitation method and cells that had incorporated the plasmid were selected by growth in the presence of mycophenolic acid to which gpt confers resistance. A number of transfectant clones were tested for tumorigenicity by inoculation into nude mice. The take incidence was variable and the tumours arose only after a prolonged latent period. Many inocula produced no tumours. These results were consistent with the view that the tumours arose by selective overgrowth of minority cell populations. Cell lines were derived by explantation of these tumours and were back-selected in 2-thioxanthine, a cytotoxic analogue of the xanthine-guanine phosphoribosyl transferase substrate. Five clones were obtained that did not express detectable levels of the c-Ha-ras 1 oncogene product, p21ras. All of them showed a less-transformed morphology than the transfected NIH 3T3 cells from which they originated. Nonetheless three of these clones were found to be tumorigenic at all sites tested. This finding demonstrates that once tumorigenic variants have been selected from the ras-transformed cells, continued production of the p21ras protein is not necessary for the maintenance of tumorigenicity. Cytogenetic analysis revealed that the transfection procedure itself introduced major and stable perturbations of the genome of the transfected cells and confirmed that tumours were produced by selective overgrowth of variants with a chromosome constitution palpably different from that of the majority of the cells injected. In the light of the complex background of genomic changes produced in NIH 3T3 cells by transfection with the c-Ha-ras 1 oncogene, no conclusion can be drawn in genetic

  9. Pulmonary neuroendocrine tumors with nuclear inclusion.

    PubMed

    Kobayashi, Saori; Tsuta, Koji; Sekine, Shigeki; Yoshida, Akihiko; Sasaki, Naoshi; Shibuki, Yasuo; Sakurai, Hiroyuki; Watanabe, Shun-Ichi; Asamura, Hisao; Tsuda, Hitoshi

    2013-09-01

    Nuclear inclusion or pseudoinclusion is a peculiar cytological feature, and its recognition in appropriate clinicopathological settings can aid in the diagnosis of several disease entities. To the best of our knowledge, only 1 case of pulmonary neuroendocrine tumor (NET) with nuclear pseudoinclusion has been reported. A review of 227 patients who had undergone surgical resection for pulmonary NETs revealed 2 tumors with different mechanisms of nuclear inclusion. To explore the cause of nuclear inclusion, NET with nuclear inclusion was characterized immunohistochemically and ultrastructurally. Nuclear inclusions were observed in 2 of the 227 (0.9%) patients with pulmonary NETs. The first patient was a 46-year-old woman with small cell carcinoma. Tumor cells with nuclear inclusions were distributed focally. Ultrastructural analysis showed that these inclusions were pseudoinclusions. The second patient was a 62-year-old man with large-cell neuroendocrine carcinoma. Nuclear inclusions were observed in the focal area of the tumor. Immunohistochemical analysis revealed that the intra-nuclear materials consisted of biotin and aberrant cytoplasmic and nuclear accumulation of β-catenin. Mutational analysis revealed a CTNNB1 gene mutation. Although very rare, diagnostic errors may be observed in cases of pulmonary NETs with nuclear inclusions. The mechanisms of nuclear inclusion differed, with one due to herniation of the cytoplasm into the nucleus (pseudoinclusion) and the other due to accumulation of biotin resulting from a CTNNB1 gene mutation. PMID:23896262

  10. Neuroendocrine effects of perfluorooctane sulfonate in rats.

    PubMed Central

    Austin, Maureen E; Kasturi, Badrinarayanan S; Barber, Matthew; Kannan, Kurunthachalam; MohanKumar, Puliyur S; MohanKumar, Sheba M J

    2003-01-01

    Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats. PMID:12948888

  11. Surgical Treatment of Neuroendocrine Liver Metastases

    PubMed Central

    Lee, Ser Yee; Cheow, Peng Chung; Teo, Jin Yao; Ooi, London L. P. J.

    2012-01-01

    Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995–2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46–86% at 5 years, 35–79% at 10 years, and the median survival ranges from 52–123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16–26 months, and the 5-year recurrence/progression rate ranges from 59–76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making. PMID:22319650

  12. Neuroendocrine control of ionic balance in zebrafish.

    PubMed

    Kwong, Raymond W M; Kumai, Yusuke; Perry, Steve F

    2016-08-01

    Zebrafish (Danio rerio) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo-ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H(+)-ATPase-rich cells for Na(+) uptake, Na(+)/K(+)-ATPase-rich cells for Ca(2+) uptake, and Na(+)/Cl(-)-cotransporter expressing cells for both Na(+) and Cl(-) uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H2S, are involved in regulating ion uptake. PMID:27179885

  13. Gestational dexamethasone alters fetal neuroendocrine axis.

    PubMed

    Ahmed, R G

    2016-09-01

    This study tested whether the maternal transport of dexamethasone (DEXA) may affect the development of the neuroendocrine system. DEXA (0.2mg/kg b.w., subcutaneous injection) was administered to pregnant rats from gestation day (GD) 1-20. In the DEXA-treated group, a decrease in maternal serum thyroxine (T4), triiodothyronine (T3), and increase in thyrotropin (TSH) levels (hypothyroid status) were observed at GDs 15 & 20 with respect to control group. The reverse pattern (hyperthyroid status) was observed in their fetuses at embryonic days (EDs) 15 & 20. Although the maternal body weight was diminished, the weight of the thyroid gland was increased at studied GDs as compared to the control group. The fetal growth retardation, hyperleptinemia, hyperinsulinism, and cytokines distortions (transforming growth factor-beta; TGF-β, tumor necrosis factor-alpha; TNF-α, and interferon-γ; IFN-γ) were noticed at examined EDs if compared to the control group. Alternatively, the maternofetal thyroid dysfunctions due to the maternal DEXA administration attenuated the levels of fetal cerebral norepinephrine (NE) and epinephrine (E), and elevated the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) at considered days. These alterations were age-dependent and might damage the nerve transmission. Finally, maternal DEXA might act as neuroendocrine disruptor causing dyshormonogenesis and fetal cerebral dysfunction. PMID:27220267

  14. Advances in the Diagnosis of Neuroendocrine Neoplasms.

    PubMed

    Kulkarni, Harshad R; Singh, Aviral; Baum, Richard P

    2016-09-01

    Somatostatin receptor PET/CT using (68)Ga-labeled somatostatin analogs, is a mainstay for the evaluation of the somatostatin receptor status in neuroendocrine neoplasms. In addition, the assessment of glucose metabolism by (18)F-FDG PET/CT at diagnosis can overcome probable shortcomings of histopathologic grading. This offers a systematic theranostic approach for the management of neuroendocrine neoplasms, that is, patient selection for the appropriate treatment-surgery, somatostatin analogs, peptide receptor radionuclide therapy, targeted therapies like everolimus and sunitinib, or chemotherapy-and also for therapy response monitoring. Novel targets, for example, the chemokine receptor CXCR4 in higher-grade tumors and glucagon like peptide-1 receptor in insulinomas, appear promising for imaging. Scandium-44 and Copper-64, especially on account of their longer half-life (for pretherapeutic dosimetry) and cyclotron production (which favors mass production), might be the potential alternatives to (68)Ga for PET/CT imaging. The future of molecular imaging lies in Radiomics, that is, qualitative and quantitative characterization of tumor phenotypes in correlation with tumor genomics and proteomics, for a personalized cancer management. PMID:27553465

  15. Therapy for metastatic pancreatic neuroendocrine tumors

    PubMed Central

    Massironi, Sara; Conte, Dario; Peracchi, Maddalena

    2014-01-01

    Background Pancreatic neuroendocrine tumors (pNETs) are frequently malignant (50-80%, except for insulinoma) and may show an aggressive course with metastases to the liver as well as more distant sites. These heterogeneous neoplasms include functioning tumors, which secrete a variety of peptide hormones, and non-functioning tumors (up to 90% of pNETs), which often show metastases at the time of diagnosis. Methods A PubMed search was performed for English-language publications from 1995 through December 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for metastatic pNETs were selected. Results The therapeutic options for metastatic pNETs are expanding and include surgery, which remains the only curative approach, liver-directed therapies, and medical therapy. In selected cases also liver transplantation (OLT) may be considered. The option of OLT for metastatic disease is unique to neuroendocrine tumors. Recently, novel promising targeted therapies have been proposed for progressive well-differentiated pNETs. Conclusions The best therapeutic approach for pNETs is still matter of debating. However, since pNETs often show a more indolent behavior compared to other malignancies, the preservation of the quality of life of the patient and the personalization of the therapy according to tumor’s and patient’s features are mandatory. PMID:25332984

  16. Neuroendocrine effects of perfluorooctane sulfonate in rats.

    PubMed

    Austin, Maureen E; Kasturi, Badrinarayanan S; Barber, Matthew; Kannan, Kurunthachalam; MohanKumar, Puliyur S; MohanKumar, Sheba M J

    2003-09-01

    Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats. PMID:12948888

  17. The impact of KRAS mutations on VEGF-A production and tumour vascular network

    PubMed Central

    2013-01-01

    Background The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile. Methods Codon13 KRAS mutation (ASP13) or codon12 KRAS mutation (CYS12) NIH3T3 transfectants were analyzed in vitro and in vivo. Expression of HIF-1α, and VEGF-A was studied at RNA and protein levels. Regulation of VEGF-A promoter activity was assessed by means of luciferase assays using different plasmid constructs. Vascular network was assessed in tumors growing after subcutaneous inoculation. Non parametric statistics were used for analysis of results. Results Our results show that in normoxic conditions ASP13 transfectants exhibited less HIF-1α protein levels and activity than CYS12. In contrast, codon 13 transfectants exhibited higher VEGF-A mRNA and protein levels and enhanced VEGF-A promoter activity. These differences were due to a differential activation of Sp1/AP2 transcription elements of the VEGF-A promoter associated with increased ERKs signalling in ASP13 transfectants. Subcutaneous CYS12 tumours expressed less VEGF-A and showed a higher microvessel density (MVD) than ASP13 tumours. In contrast, prominent vessels were only observed in the latter. Conclusion Subtle changes in the molecular nature of KRAS oncogene activating mutations occurring in tumour cells have a major impact on the vascular strategy devised providing with new insights on the role of KRAS mutations on angiogenesis. PMID:23506169

  18. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    PubMed

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-01-01

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. PMID:27257019

  19. Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours.

    PubMed

    Oberg, Kjell; Eriksson, Barbro

    2005-06-01

    Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1-3 cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as (11)C, (15)O and (18)F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with (11)C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with (131)I-MIBG is being considered. Tumour

  20. Correlation between cationic lipid-based transfection and cell division.

    PubMed

    Kirchenbuechler, Inka; Kirchenbuechler, David; Elbaum, Michael

    2016-07-01

    We evaluate the temporal relation between protein expression by cationic lipid-mediated transfection and cell division using time lapse fluorescence microscopy. Detailed image analysis provides new insights on the single cell level while simultaneously achieving appropriate statistics. Earlier evidence by less direct methods such as flow cytometry indicates a primary route for transfection involving nuclear envelope breakdown, but also suggests the existence of a pathway independent of mitosis. We confirm and quantify both mechanisms. We found the timing for successful transfection to be unexpectedly flexible, contrary to assertions of a narrow time window. Specifically, cells dividing more than 24h after exposure to the transfection medium express the probed protein at a comparable level to cells in a mitotic state during or shortly after transfection. This finding can have a profound impact on the guidance and development of non-viral gene delivery materials. PMID:25556666

  1. Unexpected transcellular protein crossover occurs during canonical DNA transfection.

    PubMed

    Arsenault, Jason; Cuijpers, Sabine A G; Niranjan, Dhevahi; Davletov, Bazbek

    2014-12-01

    Transfection of DNA has been invaluable for biological sciences, yet the effects upon membrane homeostasis are far from negligible. Here, we demonstrate that Neuro2A cells transfected using Lipofectamine LTX with the fluorescently coupled Botulinum serotype A holoenzyme (EGFP-LcA) cDNA express this SNAP25 protease that can, once translated, escape the transfected host cytosol and become endocytosed into untransfected cells, without its innate binding and translocation domains. Fluorescent readouts revealed moderate transfection rates (30-50%) while immunoblotting revealed a surprisingly total enzymatic cleavage of SNAP25; the transgenic protein acted beyond the confines of its host cell. Using intracellular dyes, no important cytotoxic effects were observed from reagent treatment alone, which excluded the possibility of membrane ruptures, though noticeably, intracellular acidic organelles were redistributed towards the plasma membrane. This drastic, yet frequently unobserved, change in protein permeability and endosomal trafficking following reagent treatment highlights important concerns for all studies using transient transfection. PMID:25043607

  2. Highly efficient transfection of human THP-1 macrophages by nucleofection.

    PubMed

    Maeß, Marten B; Wittig, Berith; Lorkowski, Stefan

    2014-01-01

    Macrophages, as key players of the innate immune response, are at the focus of research dealing with tissue homeostasis or various pathologies. Transfection with siRNA and plasmid DNA is an efficient tool for studying their function, but transfection of macrophages is not a trivial matter. Although many different approaches for transfection of eukaryotic cells are available, only few allow reliable and efficient transfection of macrophages, but reduced cell vitality and severely altered cell behavior like diminished capability for differentiation or polarization are frequently observed. Therefore a transfection protocol is required that is capable of transferring siRNA and plasmid DNA into macrophages without causing serious side-effects thus allowing the investigation of the effect of the siRNA or plasmid in the context of normal cell behavior. The protocol presented here provides a method for reliably and efficiently transfecting human THP-1 macrophages and monocytes with high cell vitality, high transfection efficiency, and minimal effects on cell behavior. This approach is based on Nucleofection and the protocol has been optimized to maintain maximum capability for cell activation after transfection. The protocol is adequate for adherent cells after detachment as well as cells in suspension, and can be used for small to medium sample numbers. Thus, the method presented is useful for investigating gene regulatory effects during macrophage differentiation and polarization. Apart from presenting results characterizing macrophages transfected according to this protocol in comparison to an alternative chemical method, the impact of cell culture medium selection after transfection on cell behavior is also discussed. The presented data indicate the importance of validating the selection for different experimental settings. PMID:25226503

  3. Highly Efficient Transfection of Human THP-1 Macrophages by Nucleofection

    PubMed Central

    Maeß, Marten B.; Wittig, Berith; Lorkowski, Stefan

    2014-01-01

    Macrophages, as key players of the innate immune response, are at the focus of research dealing with tissue homeostasis or various pathologies. Transfection with siRNA and plasmid DNA is an efficient tool for studying their function, but transfection of macrophages is not a trivial matter. Although many different approaches for transfection of eukaryotic cells are available, only few allow reliable and efficient transfection of macrophages, but reduced cell vitality and severely altered cell behavior like diminished capability for differentiation or polarization are frequently observed. Therefore a transfection protocol is required that is capable of transferring siRNA and plasmid DNA into macrophages without causing serious side-effects thus allowing the investigation of the effect of the siRNA or plasmid in the context of normal cell behavior. The protocol presented here provides a method for reliably and efficiently transfecting human THP-1 macrophages and monocytes with high cell vitality, high transfection efficiency, and minimal effects on cell behavior. This approach is based on Nucleofection and the protocol has been optimized to maintain maximum capability for cell activation after transfection. The protocol is adequate for adherent cells after detachment as well as cells in suspension, and can be used for small to medium sample numbers. Thus, the method presented is useful for investigating gene regulatory effects during macrophage differentiation and polarization. Apart from presenting results characterizing macrophages transfected according to this protocol in comparison to an alternative chemical method, the impact of cell culture medium selection after transfection on cell behavior is also discussed. The presented data indicate the importance of validating the selection for different experimental settings. PMID:25226503

  4. Transfection of isolated rainbow trout, Oncorhynchus mykiss, granulosa cells through chemical transfection and electroporation at 12°C.

    PubMed

    Marivin, E; Mourot, B; Loyer, P; Rime, H; Bobe, J; Fostier, A

    2015-09-15

    Over-expression or inhibition of gene expression can be efficiently used to analyse the functions and/or regulation of target genes. Modulation of gene expression can be achieved through transfection of exogenous nucleic acids into target cells. Such techniques require the development of specific protocols to transfect cell cultures with nucleic acids. The aim of this study was to develop a method of transfection suitable for rainbow trout granulosa cells in primary culture. After the isolation of rainbow trout granulosa cells, chemical transfection of cells with a fluorescent morpholino oligonucleotide (MO) was tested using FuGENE HD at 12 °C. Electroporation was also employed to transfect these cells with either a plasmid or MO. Transfection was more efficient using electroporation (with the following settings: 1200 V/40 ms/1p) than chemical transfection, but electroporation by itself was deleterious, resulting in a decrease of the steroidogenic capacity of the cells, measured via estradiol production from its androgenic substrate. The disturbance of cell biology induced by the transfection method per se should be taken into account in data interpretation when investigating the effects of under- or over-expression of candidate genes. PMID:25957917

  5. Neuroendocrine and immune system responses with spaceflights.

    PubMed

    Tipton, C M; Greenleaf, J E; Jackson, C G

    1996-08-01

    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), aldosterone, 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-flights data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  6. Metabolic reprogramming of the tumour microenvironment.

    PubMed

    Xing, Yazhi; Zhao, Shimin; Zhou, Binhua P; Mi, Jun

    2015-10-01

    Tumour cells, stromal cells and the stroma comprise the tumour microenvironment. The metabolism of both tumour cells and several types of tumour stromal cells, such as cancer-associated fibroblasts and tumour-associated macrophages, is reprogrammed. Current studies have found that stromal cells promote tumour progression and metastasis, through not only the paracrine secretion of cytokines or chemokines, but also intermediate metabolites. Here, we summarize the latest insights into the mechanism of metabolic reprogramming in cancer cells, cancer-associated fibroblasts and tumour-associated macrophages, and their potential roles in tumour progression and metastasis. PMID:26255648

  7. One very rare and one new tracheal tumour found by electron microscopy: glomus tumour and acinic cell tumour resembling carcinoid tumours by light microscopy.

    PubMed Central

    Heard, B E; Dewar, A; Firmin, R K; Lennox, S C

    1982-01-01

    Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract. Images PMID:6281934

  8. Electroporation for Transfection and Differentiation of Dental Pulp Stem Cells

    PubMed Central

    Rabie, Bakr M.

    2013-01-01

    Abstract Target gene delivery is needed to induce cellular differentiation or a specific therapeutic effect. Electroporation is a relatively safe and simple technique to deliver nucleic acids to the cell that acts by rendering cells transiently permeable using short periods of high voltage. In stem cell research, human dental pulp stem cells (hDPSCS) are highly accessible, and they exhibit broad differentiation potential. Until now, no studies have attempted to optimize electroporation parameters for DPSCs with respect to transfection efficiency and viability. In this study, we aimed to optimize transfection of DPSCs through varying different electroporation parameters, including voltage, mode of pulsation, and the number of pulses. As positive control, we used commonly utilized the chemical transfection reagents Lipofectamine 2000 and FuGene 6. In addition, we used our newly optimized transfection conditions to transfect hDPSCs with a functional chondrogenic transgene. We obtained higher transfection efficiency and cell viability with these electroporation conditions compared to controls. The highest transfection efficiency (63.81±4.72%) was achieved with 100 V, 20 msec, one-pulse square-wave condition. Among chemical transfection groups, FuGene 6 showed the highest cell viability at all tested transfection ratios, while Lipofectamine 2000 showed the highest transfection efficiency (19.23±3.19%) using 1:1 DNA (μg):Lipofectamine (μL). Transfected DPSCs functionally expressed the transforming growth factor β-3 chondrogenic transgene on the mRNA level as detected by real-time polymerase chain reaction and on the protein level as detected by Western blot analysis. An increase in various chondrogenic markers was also found when studying mRNA expression in transfected cells. In conclusion, the results of our study demonstrate optimal electroporation and chemical transfection reagent conditions for hDPSCs, and, subsequently, we provide proof of concept for

  9. Recurrent hyperphosphatemic tumoural calcinosis

    PubMed Central

    Amit, Sonal; Agarwal, Asha; Nigam, Anand; Rao, Yashwant Kumar

    2012-01-01

    Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint. PMID:23010461

  10. Use of molecular targeted agents for the diagnosis, staging and therapy of neuroendocrine malignancy

    PubMed Central

    2010-01-01

    Abstract Imaging of neuroendocrine tumours (NET) poses significant challenges because of the heterogeneous biology of the tumours that are represented by this class of neoplasia. NET can range from benign lesions to highly aggressive cancers. Structural imaging techniques have suboptimal sensitivity in most published series and diagnosis is often delayed until metastatic disease is present. Current guidelines emphasise the importance of functional imaging for evaluating the extent of NET. The mainstay of this type of imaging has been somatostatin receptor scintigraphy (SRS) with [111In]diethylenetriaminepentaacetic acid-octreotide (Octreoscan™). Routine use of single-photon emission computed tomography (SPECT) and particularly of hybrid SPECT/computed tomography (CT) has significantly improved localisation of tumour sites and evaluation of somatostatin receptor (SSTR) expression, which is important for predicting the likelihood of response to somatostatin analogues (SSA). Positron emission tomography (PET) can also now be used for evaluating SSTR expression. There are a number of peptides that have been evaluated but [68Ga]tetraazocyclodecanetetraacetic acid (DOTA)-octreotate (GaTate) PET/CT, which has been shown to be significantly more sensitive for detecting small lesions than Octreoscan™, is now probably the preferred agent because high uptake in known sites of disease provides a diagnostic pair for assessing suitability of patients for [177Lu]DOTA-octreotate (LuTate) peptide receptor radionuclide therapy (PRRT). A range of other radiolabelled SSA has also been used for PRRT. Lesions without SSTR expression require alternative imaging and therapeutic strategies. Although fluorodeoxyglucose (FDG) uptake in low-grade NET is not generally increased relative to normal tissues, the loss of differentiation that often accompanies loss of SSTR expression may be associated with a significant increase in glycolytic metabolism and an accompanying improvement in the