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Sample records for pituitary tumor cells

  1. Pituitary Tumors

    Science.gov (United States)

    ... institutes of the National Institutes of Health (NIH) conduct research related to brain tumors, including pituitary tumors, in their laboratories at ... institutes of the National Institutes of Health (NIH) conduct research related to brain tumors, including pituitary tumors, in their laboratories at ...

  2. Pituitary tumor

    Science.gov (United States)

    ... enough of its hormones. This condition is called hypopituitarism . The causes of pituitary tumors are unknown. Some ... Cyst Endocrine glands Gigantism Growth hormone test Hyperthyroidism Hypopituitarism Multiple endocrine neoplasia (MEN) I Prolactin blood test ...

  3. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  4. Pituitary Tumors: Condition Information

    Science.gov (United States)

    ... and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do not produce hormones. They can press on or damage the pituitary ...

  5. Pituitary Tumors

    Science.gov (United States)

    ... impairment, and behavioral changes. Tumors can also either produce excessive amounts of hormone or limit how much hormone is produced. The hormones most commonly affected include: growth hormone (regulates body height and structure), prolactin (controls ...

  6. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained...

  7. Familial pituitary tumor syndromes.

    Science.gov (United States)

    Elston, Marianne S; McDonald, Kerrie L; Clifton-Bligh, Roderick J; Robinson, Bruce G

    2009-08-01

    The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.

  8. Mechanisms for growth factor-induced pituitary tumor transforming gene-1 expression in pituitary folliculostellate TtT/GF cells.

    Science.gov (United States)

    Vlotides, G; Cruz-Soto, M; Rubinek, T; Eigler, T; Auernhammer, C J; Melmed, S

    2006-12-01

    PTTG1, a securin protein, also behaves as a transforming gene and is overexpressed in pituitary tumors. Because pituitary folliculostellate (FS) cells regulate pituitary tumor growth factors by paracrine mechanisms, epidermal growth factor (EGF) receptor (EGFR)-mediated PTTG1 expression and cell proliferation was tested in pituitary FS TtT/GF cells. EGFR ligands caused up to 3-fold induction of Pttg1 mRNA expression, enhanced proliferating cell nuclear antigen, and increased entry of G0/1-arrested cells into S-phase. PTTG binding factor mRNA expression was not altered. EGF-induced Pttg1 expression and cell proliferation was abolished by preincubation of TtT/GF cells with EGFR inhibitors AG1478 and gefitinib. Phosphatidylinositol 3 kinase, protein kinase C, and MAPK, but not c-Jun N-terminal kinase and Janus activating kinase signaling regulated EGF-induced Pttg1, as well as proliferating cell nuclear antigen mRNA expression and entry into S-phase. EGF-induced EGFR and ERK1/2 phosphorylation was followed by rapid MAPK kinase/ERK kinase-dependent activation of Elk-1 and c-Fos. EGF-induced Pttg1 expression peaked at the S-G2 transition and declined thereafter. Pttg1 cell cycle dependency was confirmed by suppression of EGF-induced Pttg1 mRNA by blockade of cells in early S-phase. The results show that PTTG1 and its binding protein PTTG binding factor are expressed in pituitary FS TtT/GF cells. EGFR ligands induce PTTG1 and regulate S-phase, mediated by phosphatidylinositol 3 kinase, protein kinase C, and MAPK pathways. PTTG1 is therefore a target for EGFR-mediated paracrine regulation of pituitary cell growth.

  9. General Information about Pituitary Tumors

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    ... Tumors Treatment Pituitary Tumors Treatment (PDQ®)–Patient Version General Information About Pituitary Tumors Go to Health Professional ... by many other glands in the body. Enlarge Anatomy of the inside of the brain, showing the ...

  10. Pituitary gland tumors; Hypophysentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)

    2014-10-15

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  11. Antiapoptotic factor humanin is expressed in normal and tumoral pituitary cells and protects them from TNF-α-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    María Florencia Gottardo

    Full Text Available Humanin (HN is a 24-amino acid peptide with cytoprotective action in several cell types such as neurons and testicular germ cells. Rattin (HNr, a homologous peptide of HN expressed in several adult rat tissues, also has antiapoptotic action. In the present work, we demonstrated by immunocytochemical analysis and flow cytometry the expression of HNr in the anterior pituitary of female and male adult rats as well as in pituitary tumor GH3 cells. HNr was localized in lactotropes and somatotropes. The expression of HNr was lower in females than in males, and was inhibited by estrogens in pituitary cells from both ovariectomized female and orquidectomized male rats. However, the expression of HNr in pituitary tumor cells was not regulated by estrogens. We also evaluated HN action on the proapoptotic effect of TNF-α in anterior pituitary cells assessed by the TUNEL method. HN (0.5 µM per se did not modify basal apoptosis of anterior pituitary cells but completely blocked the proapoptotic effect of TNF-α in total anterior pituitary cells, lactotropes and somatotropes from both female and male rats [corrected]. Also, HN inhibited the apoptotic effect of TNF-α on pituitary tumor cells. In summary, our results demonstrate that HNr is present in the anterior pituitary gland, its expression showing sexual dimorphism, which suggests that gonadal steroids may be involved in the regulation of HNr expression in this gland. Antiapoptotic action of HN in anterior pituitary cells suggests that this peptide could be involved in the homeostasis of this gland. HNr is present and functional in GH3 cells, but it lacks regulation by estrogens, suggesting that HN could participate in the pathogenesis of pituitary tumors.

  12. Luteinizing hormone (LH) and prolactin-releasing pituitary tumor: possible malignant transformation of the LH cell line.

    Science.gov (United States)

    Spertini, F; Deruaz, J P; Perentes, E; Pelet, B; Gomez, F

    1986-05-01

    A pituitary tumor was diagnosed in a prepubertal 13-yr-old girl, who had elevated plasma LH (58 mIU/ml) and PRL (93 ng/ml) levels; decreased GH, ACTH, and FSH secretion; and diabetes insipidus. After surgery, plasma LH and PRL declined, but not to normal levels. Conventional external radiotherapy to the pituitary was immediately followed by a decrease in LH to prepubertal values (0.7 mIU/ml), while PRL levels became normal only after a long course of bromocriptine therapy. The pituitary tumor was composed of two distinct cell types: small polygonal cells, which were PRL positive by immunohistochemistry, and clusters of pleomorphic large frequently mitotic polynucleated cells, which were LH positive, some of them also being positive for the alpha-subunit or beta LH but not for beta FSH. Four years after surgery and radiotherapy, the patient deteriorated neurologically. Computed tomographic scan showed widespread frontal and periventricular tumor, which had the histological features of a poorly differentiated carcinoma. No PRL, LH, or alpha- or beta-subunits were detectable on immunocytochemistry. While the PRL-positive cells of the pituitary tumor displayed the histological and clinical features of PRL adenomas, the morphological characteristics of LH cells and the sharp decline of plasma LH levels after radiotherapy were suggestive of malignant transformation. In this context, the later brain tumor could have been the result of subependymal spread of the pituitary tumor after it lost its hormone-secreting capacity.

  13. Subarachnoid hemorrhage in pituitary tumor

    Directory of Open Access Journals (Sweden)

    Ashis Patnaik

    2013-01-01

    Full Text Available Subarachnoid hemorrhage (SAH is the bleeding into the subarachnoid space containing cerebrospinal fluid. The most common cause of SAH is trauma. Rupture of aneurysms, vascular anomalies, tumor bleeds and hypertension are other important etiologies. SAH in the setting of pituitary tumor can result from various causes. It can be due to intrinsic tumor related pathology, injury to surrounding the vessel during the operative procedure or due to an associated aneurysm. We discuss the pathological mechanisms and review relevant literature related to this interesting phenomenon. Early and accurate diagnosis of the cause of the SAH in pituitary tumors is important, as this influences the management.

  14. What Are Pituitary Tumors?

    Science.gov (United States)

    ... grow and to make steroid hormones (such as cortisol). Too much ACTH from the pituitary causes Cushing’s ... Cancer Atlas Press Room Cancer Statistics Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, ...

  15. Membrane estrogen receptor-α-mediated nongenomic actions of phytoestrogens in GH3/B6/F10 pituitary tumor cells

    OpenAIRE

    Jeng, Yow-Jiun; Kochukov, Mikhail Y.; Watson, Cheryl S

    2009-01-01

    Background: Estradiol (E2) mediates various intracellular signaling cascades from the plasma membrane via several estrogen receptors (ERs). The pituitary is an estrogen-responsive tissue, and we have previously reported that E2 can activate mitogen-activated protein kinases (MAPKs) such as ERK1/2 and JNK1/2/3 in the membrane ERα (mERα)-enriched GH3/B6/F10 rat pituitary tumor cell line. Phytoestrogens are compounds found in plants and foods such as soybeans, alfalfa sprouts, and red grapes. Th...

  16. Regulation of pituitary tumor transforming gene (PTTG) expression and phosphorylation in thyroid cells.

    Science.gov (United States)

    Lewy, Gregory D; Ryan, Gavin A; Read, Martin L; Fong, Jim C W; Poole, Vikki; Seed, Robert I; Sharma, Neil; Smith, Vicki E; Kwan, Perkin P K; Stewart, Sarah L; Bacon, Andrea; Warfield, Adrian; Franklyn, Jayne A; McCabe, Christopher J; Boelaert, Kristien

    2013-11-01

    Human pituitary tumor transforming gene (hPTTG) is a multifunctional proto-oncogene implicated in the initiation and progression of several tumors. Phosphorylation of hPTTG is mediated by cyclin-dependent kinase 2 (CDC2), whereas cellular expression is regulated by specificity protein 1 (SP1). The mechanisms underlying hPTTG propagation of aberrant thyroid cell growth have not been fully defined. We set out to investigate the interplay between hPTTG and growth factors, as well as the effects of phosphorylation and SP1 regulation on hPTTG expression and function. In our study, epidermal growth factor (EGF), TGFα, and IGF-1 induced hPTTG expression and phosphorylation in thyroid cells, which was associated with activation of MAPK and phosphoinositide 3-kinase. Growth factors induced hPTTG independently of CDC2 and SP1 in thyroid carcinoma cells. Strikingly, CDC2 depletion in TPC-1 cells resulted in enhanced expression and phosphorylation of hPTTG and reduced cellular proliferation. In reciprocal experiments, hPTTG overexpression induced EGF, IGF-1, and TGFα mRNAs in primary human thyrocytes. Treatment of primary human thyrocytes with conditioned media derived from hPTTG-transfected cells resulted in autocrine upregulation of hPTTG protein, which was ameliorated by growth factor depletion or growth factor receptor tyrosine kinase inhibitors. A transgenic murine model of thyroid targeted hPTTG overexpression (hPTTG-Tg) (FVB/N strain, both sexes) demonstrated smaller thyroids with reduced cellular proliferation and enhanced secretion of Egf. In contrast, Pttg(-/-) knockout mice (c57BL6 strain, both sexes) showed reduced thyroidal Egf mRNA expression. These results define hPTTG as having a central role in thyroid autocrine signaling mechanisms via growth factors, with profound implications for promotion of transformed cell growth.

  17. Nonadenomatous tumors of the pituitary and sella turcica.

    Science.gov (United States)

    Huang, Benjamin Y; Castillo, Mauricio

    2005-07-01

    While pituitary adenomas make up over 90% of all sellar masses, there are a number of less known tumors, both malignant and benign, which may arise within the sella turcica. These include relatively common tumors such as meningiomas and craniopharyngiomas, as well as extremely rare tumors such as pituitary astrocytomas and granular cell tumors. Unfortunately, many of these tumors lack characteristic imaging features, often making it extremely difficult to distinguish them by imaging alone from the more common pituitary adenoma. In this article, we review several nonadenomatous tumors of the sella, with a focus on their clinical features and typical MR imaging characteristics.

  18. Autocrine IL-6 mediates pituitary tumor senescence

    Science.gov (United States)

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

    2017-01-01

    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  19. Rheumatic manifestations of pituitary tumors.

    Science.gov (United States)

    Stavrou, S; Kleinberg, D L

    2001-10-01

    Pituitary tumors may cause rheumatologic problems as a result of under production or overproduction of one pituitary hormone. Excessive growth hormone causes destruction of cartilage by a direct action. Facial and acral changes and arthralgias may be some of the first symptoms of acromegaly. The arthritis associated with acromegaly is often devastating. Carpal tunnel syndrome is very common in patients with acromegaly. Adrenocorticotropin (ACTH) has indirect effects via the action of glucocorticoid on bones, muscles, and the immune system. Proximal muscle weakness is a characteristic feature of Cushing's syndrome. Patients with Cushing's syndrome commonly have osteopenia and osteoporosis that lead to an increase in bone fractures. Avascular necrosis is associated with exogenous steroid administration. The effects of too much glucocorticoid or too rapid withdrawal can be severe. Gonadotropins act via the gonadal steroids and protect bone mass from loss. Prolactin is less involved in rheumatologic disease; the data for which are limited in humans. Pituitary tumors can have manifestations similar to rheumatologic disorders and should be included in the differential diagnosis of these diseases.

  20. Pituitary tumor evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Albertson, B.; Binney, S.

    1995-11-01

    This paper describes research on the following: the structure of {sup 10}B{sub 10}-ovine corticotropin releasing hormone and {sup 10}B{sub 10}-growth hormone releasing hormone; the BNCT effect on AtT-20 cell {sup 10}B{sub 10}-CRH incubations in vitro; BNCT effects on GH{sub 4}C{sub 1} cell {sup 10}B{sub 10} growth hormone releasing factor incubation in vitro; and competitive inhibition of AtT-20 cell BNCT effect.

  1. What Are the Symptoms of Pituitary Tumors?

    Science.gov (United States)

    ... Clinical Trials Resources and Publications What are the symptoms of pituitary tumors? Skip sharing on social media links Share this: Page Content Symptoms of Functioning Tumors The symptoms of functioning tumors ...

  2. Human chorionic somatomammotropin and growth hormone gene expression in rat pituitary tumor cells is dependent on proximal promoter sequences

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    Nachtigal, M.W.; Nickel, B.E.; Klassen, M.E.; Cattini, P.A. (Univ. of Manitoba, Winnipeg (Canada)); Zhang, Wengang; Eberhardt, N.L. (Univ. of California, San Francisco (USA))

    1989-06-12

    Human placental chorionic somatomammotropin (hCS-A or hCS-B) and pituitary growth hormone (hGH-N) are related by structure and function. The hCS-A gene is expressed in rat pituitary tumor (GC) cells after gene transfer. Deletion of hCS-A 5{prime}-flanking DNA reveals repressor activity upstream of nucleotide {minus}132, and a region essential for expression in GC cells between nucleotides {minus}94 and {minus}61. The sequences in this region differ from the equivalent hGH-N gene DNA by one nucleotide, and include the binding site for a pituitary-specific factor (GHF-1), required for hGH-N expression in GC cells. Exchange of hGH-N with hCS-A gene DNA in this region maintains expression in GC cells. By contrast, modification of these sequences blocks expression. These data indicate that proximal promoter sequences, equivalent to those bound by GHF-1 on the hGH-N gene, are required for hCS-A expression in GC cells.

  3. HMGA1-pseudogene expression is induced in human pituitary tumors

    Science.gov (United States)

    Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; Mussnich, Paula; Raverot, Gerald; Jaffrain-Rea, Marie-Lise; Fraggetta, Filippo; Trouillas, Jacqueline; Fusco, Alfredo

    2015-01-01

    Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis. PMID:25894544

  4. Tubocurarine blocks a calcium-dependent potassium current in rat tumoral pituitary cells.

    Science.gov (United States)

    Vacher, P; Vacher, A M; Mollard, P

    1998-04-30

    We investigated the effects of potassium channel inhibitors on electrical activity, membrane ionic currents, intracellular calcium concentration ([Ca2+]i) and hormone release in GH3/B6 cells (a line of pituitary origin). Patch-clamp recordings show a two-component after hyperpolarization (AHP) following each action potential (current clamp) or a two-component tail current (voltage-clamp). Both components can be blocked by inhibiting Ca2+ influx. Application of D-tubocurarine (dTc) (20-500 microM) reversibly suppressed the slowly decaying Ca2+-activated K+ tail current (I AHPs) in a concentration-dependent manner. On the other hand, low doses of tetraethylammonium ions (TEA+) only blocked the rapidly decaying voltage- and Ca2+-activated K+ tail current (I AHPf). Therefore, GH3/B6 cells exhibit at least two quite distinct Ca2+-dependent K+ currents, which differ in size, voltage- and Ca2+-sensitivity, kinetics and pharmacology. These two currents also play quite separate roles in shaping the action potential. d-tubocurarine increased spontaneous Ca2+ action potential firing, whereas TEA increased action potential duration. Thus, both agents stimulated Ca2+ entry. I AHPs is activated by a transient increase in [Ca2+]i such as a thyrotrophin releasing hormone-induced Ca2+ mobilization. All the K+ channel inhibitors we tested: TEA, apamin, dTC and charybdotoxin, stimulated prolactin and growth hormone release in GH3/B6 cells. Our results show that I AHPs is a good sensor for subplasmalemmal Ca2+ and that dTc is a good pharmacological tool for studying this current.

  5. Recent advances in pituitary tumor management.

    Science.gov (United States)

    Winder, Mark J; Mayberg, Marc R

    2011-08-01

    Advances in the neurosurgical management of pituitary tumors have included the refinement of surgical access and significant progress in navigation technology to help further reduce morbidity and improve outcome. Similarly, stereotactic radiosurgery has evolved to become an integral part in pituitary tumors not amenable to medical or surgical treatment. The evolution of minimally invasive surgery has evolved toward endoscopic versus microscopic trans-sphenoidal approaches for pituitary tumors. Debate exists regarding each approach, with advocates for both championing their cause. Stereotactic and fractional radiosurgery have been shown to be a safe and effective means of controlling tumor growth and ensuring hormonal stabilization, with longer-term data available for GammaKnife compared with CyberKnife. The advances in trans-sphenoidal surgical approaches, navigation technological improvements and the current results of stereotactic radiosurgery are discussed.

  6. Thyroxine 5'-deiodinase in human anterior pituitary tumors.

    Science.gov (United States)

    Itagaki, Y; Yoshida, K; Ikeda, H; Kaise, K; Kaise, N; Yamamoto, M; Sakurada, T; Yoshinaga, K

    1990-08-01

    The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

  7. Hydrogen sulfide induces hyperpolarization and decreases the exocytosis of secretory granules of rat GH3 pituitary tumor cells.

    Science.gov (United States)

    Mustafina, Alsu N; Yakovlev, Aleksey V; Gaifullina, Aisylu Sh; Weiger, Thomas M; Hermann, Anton; Sitdikova, Guzel F

    2015-10-02

    The aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16-19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (KATP) by glibenclamide or by diazoxide, respectively. In whole-cell recordings NaHS increased the amplitude of KATP currents, induced by hyperpolarizing pulses and subsequent application of glibenclamide decreased currents to control levels. Using the fluorescent dye FM 1-43 exocytosis of secretory granules was analyzed in basal and stimulated conditions (high K(+) external solution). Prior application of NaHS decreased the fluorescence of the cell membrane in both conditions which links with activation of KATP currents (basal secretion) and activation of KATP currents and BK-currents (stimulated exocytosis). We suggest that H2S induces hyperpolarization of GH3 cells by activation of KATP channels which results in a truncation of spontaneous action potentials and a decrease of hormone release.

  8. Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3 Cells

    Directory of Open Access Journals (Sweden)

    Edmund Cheung So

    2017-04-01

    Full Text Available Background: Artemisinin (ART is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs in pituitary tumor (GH3 cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR with an IC50 value of 11.2 µM and enhanced IK(DR inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM or iloprost (100 nM did not alter the magnitude of ART-induced inhibition of IK(DR in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both IK(DR and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

  9. Non-functioning pituitary tumors: 2012 update.

    Science.gov (United States)

    Cámara Gómez, Rosa

    2014-03-01

    Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes>4cm(3). Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long-term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  10. Radiation Therapy of Pituitary Tumors

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    Park, Moon Baik; Hong, Seong Eong [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients.

  11. Negative regulation of human growth hormone gene expression by insulin is dependent on hypoxia-inducible factor binding in primary non-tumor pituitary cells.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Cattini, Peter A

    2012-09-28

    Insulin controls growth hormone (GH) production at multiple levels, including via a direct effect on pituitary somatotrophs. There are no data, however, on the regulation of the intact human (h) GH gene (hGH1) by insulin in non-tumor pituitary cells, but the proximal promoter region (nucleotides -496/+1) responds negatively to insulin in transfected pituitary tumor cells. A DNA-protein interaction was also induced by insulin at nucleotides -308/-235. Here, we confirmed the presence of a hypoxia-inducible factor 1 (HIF-1) binding site within these sequences (-264/-259) and investigated whether HIF-1 is associated with insulin regulation of "endogenous" hGH1. In the absence of primary human pituitary cells, transgenic mice expressing the intact hGH locus in a somatotroph-specific manner were generated. A significant and dose-dependent decrease in hGH and mouse GH RNA levels was detected in primary pituitary cell cultures from these mice with insulin treatment. Increasing HIF-1α availability with a hypoxia mimetic significantly decreased hGH RNA levels and was accompanied by recruitment of HIF-1α to the hGH1 promoter in situ as seen with insulin. Both inhibition of HIF-1 DNA binding by echinomycin and RNA interference of HIF-1α synthesis blunted the negative effect of insulin on hGH1 but not mGH. The insulin response is also sensitive to histone deacetylase inhibition/trichostatin A and associated with a decrease in H3/H4 hyperacetylation in the proximal hGH1 promoter region. These data are consistent with HIF-1-dependent down-regulation of hGH1 by insulin via chromatin remodeling specifically in the proximal promoter region.

  12. [Pituitary tumors manifesting with amenorrhea-galactorrhea].

    Science.gov (United States)

    Bartal, A; Razon, N

    1976-05-16

    The amenorrhea-galactorrhea syndrome which occurs at a time other than the post-partum period is most often seen in association with a tumor of the pituitary gland; the symptoms are caused by a hypersecretion of prolactin. Among a series of 19 patients in Tel Aviv who underwent surgery for treatment of pituitary tumors, 2 presented with the amenorrhea-galactorrhea syndrome. The first patient, a 16 year old, presented with headaches, nausea, and diplopia; she underwent a series of 3 surgical procedures and died of a respiratory arrest in the third post-operative period. The second patient was a 39 year old woman who had borne 5 children; she presented with loss of vision, underwent surgery, and did well post-operatively. The authors point out that whereas either amenorrhea or galactorrhea alone may be associated with a number of disorders, the combination of the two symptoms is characteristic of pituitary tumors. Both patients who were presented in this article had chromophobe adenomas of the pituitary. The authors also discuss the various biologic actions of prolactin and its interrelationships with other hormones.

  13. Management of incidental pituitary tumors

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    Nicholas F. Marko

    2011-11-01

    Full Text Available Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1 is the lesion causing neurological symptoms, and (2 is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

  14. How Are Pituitary Tumors Diagnosed?

    Science.gov (United States)

    ... secreting tumor. Levels of related hormones, such as estrogen, progesterone, and testosterone, are often checked as well. Thyrotropin-secreting adenoma Tests to measure blood levels of thyrotropin (TSH) and thyroid hormones can usually identify people with a thyrotropin- ...

  15. Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

    Science.gov (United States)

    Willems, Christophe; Vankelecom, Hugo

    2014-01-01

    The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

  16. The influence of the pituitary tumor transforming gene-1 (PTTG-1 on survival of patients with small cell lung cancer and non-small cell lung cancer

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    Geddert Helene

    2006-01-01

    Full Text Available Abstract Background PTTG-1 (pituitary tumor transforming gene is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Methods Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC and 91 patients with non-small cell lung cancer (NSCLC, retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. Results PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 ± 18 days vs. 379 ± 66 days; p = 0.0291. Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 ± 58 days compared with 463 ± 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386. Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Conclusion Lung cancers belong to the group of tumors expressing

  17. [Prognostic implications of folliculo-stellate cells in pituitary adenomas: relationship with tumoral behavior].

    Science.gov (United States)

    Tortosa, F; Pires, M; Ortiz, S

    2016-10-01

    Introduccion. A pesar del progreso en la comprension de su patogenia, no se ha encontrado ningun marcador predictivo independiente del comportamiento agresivo de los adenomas hipofisarios que facilite el tratamiento y seguimiento de pacientes afectados. Objetivo. Analizar la expresion de celulas foliculo-estrelladas, mediante inmunomarcacion con proteina S-100, en una serie de pacientes con adenomas hipofisarios seguidos durante al menos siete años. Pacientes y metodos. Estudio retrospectivo de 51 pacientes diagnosticados de adenoma hipofisario entre 2006 y 2008, segun los criterios vigentes de la Organizacion Mundial de la Salud. Se evaluo inmunohistoquimicamente la expresion de S-100 en celulas foliculo-estrelladas, y se correlaciono con parametros clinicorradiologicos e histopatologicos del tumor y la progresion/recurrencia postoperatoria. Resultados. De 51 tumores, 40 se clasificaron como adenomas hipofisarios tipicos y 11 como atipicos. La mayoria de los tipicos mostro celulas foliculo-estrelladas positivas para S-100 (media: 3,93%); los atipicos tenian pocas o ninguna celula S-100 positivas (media: 0,83%). No hubo diferencias significativas en la expresion de S-100 con respecto a la edad o sexo del paciente, tamaño, invasividad o recidiva tumoral posquirurgica. Conclusiones. En el grupo de estudio, a excepcion de los adenomas no funcionantes inmunopositivos para prolactina, con la media mas baja y mas alta de todos los subtipos en ambos grupos (tipicos, 0,25%, frente a atipicos, 9,24%; p = 0,0028), el factor predictivo de agresividad tumoral para los adenomas hipofisarios no esta representado por un bajo valor de S-100 en las celulas foliculo-estrelladas, lo que no permite seleccionar a pacientes para un tratamiento postoperatorio intensivo.

  18. Endoscopic transnasal approach for removing pituitary tumors

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    Mirian Cabral Moreira de Castro

    2014-05-01

    Full Text Available To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42% and secreting in 33 patients (22.58%. Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%, followed by the prolactinoma, (6.98%. Eleven patients developed cerebral spinal fluid (CSF fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated.

  19. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the role of growth factor autocrine stimulation in the pathogenesis of human pituitary tumors. Methods: The expression of EGF, TGF-a and EGFR were studied by immunohisto-chemical method on paraffin-embedded sections of 30 cases pituitary tumor. Results: EGFR and its ligands EGF, TGF-a expressed in majority of pituitary tumors. The expression of EGFR and its ligands varied with cells' intensity, density and type. Conclusion: The EGF autocrine stimulating exerted in the pituitary tumor development process, that tyrosine kinases inhibitors may be useful for pituitary tumors treatment.

  20. Respiration rate in human pituitary tumor explants.

    Science.gov (United States)

    Anniko, M; Bagger-Sjöbäck, D; Hultborn, R

    1982-01-01

    Studies on the respiration rate of human pituitary tumor tissue have so far been lacking in the literature. This study presents the results from four adenomas causing acromegaly, all with different clinical degrees of the disease. Determination of oxygen uptake was performed in vitro with a spectrophotorespirometric system. Pieces of the tumors were explanted to an organ culture system with a high degree of stability. The secretion rate of growth hormone (GH) and prolactin (PRL) was determined. After 4-8 days in vitro, specimens were analyzed for respiration rate. This was approximately 1-1.5 microliters O2/h/micrograms dry weight. The activity of the pituitary tumor tissue was characterized by both the hormone secretion rate and the respiration rate. Particularly active foci were found to occur in the adenoma tissue. Depending on the individual tumor, the GH secretion rate was approximately 0.1-100 pmol/micrograms dry weight/h and PRL secretion rate approximately 0.4-18 micrograms/micrograms dry weight/h. The respiration rate--as is also the hormone secretion rate--is dependent on the time in vitro prior to analysis. The respiration rate in individual tumors is a parameter which does not reflect GH or PRL serum levels or clinical activity of the disease.

  1. Pituitary tumor apoplexy Apoplexia em tumor hipofisário

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    Claudia V. Chang

    2009-06-01

    Full Text Available Pituitary tumor apoplexy is a medical emergency due to acute infarction or hemorrhage in the pituitary gland. In this review, the authors discuss the sellar anatomy, the pituitary gland and adenomas' vascularization and the general aspects of the syndrome such as its ethiopatogenesis, predisposing factors, clinical features, treatment and prognosis.A apoplexia em tumor hipofisário é uma emergência médica decorrente do infarto agudo ou hemorrágico na glândula hipófise. Nesta revisão os autores discutem a anatomia da região selar, a vascularização da hipófise e adenomas hipofisários, e demais aspectos da síndrome como etiopatogenia, fatores predisponentes, quadro clínico, tratamento e prognóstico.

  2. Pituitary macroadenoma presenting as a nasal tumor: case report

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    Nivaldo Adolfo Silva Junior

    Full Text Available CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass.CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases.CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.

  3. Characterization of a pituitary-tumor-derived cell line, TtT/GF, that expresses Hoechst efflux ABC transporter subfamily G2 and stem cell antigen 1.

    Science.gov (United States)

    Mitsuishi, Hideo; Kato, Takako; Chen, Mo; Cai, Li-Yi; Yako, Hideji; Higuchi, Masashi; Yoshida, Saishu; Kanno, Naoko; Ueharu, Hiroki; Kato, Yukio

    2013-11-01

    The anterior lobe of the pituitary gland is composed of five types of endocrine cells and of non-endocrine folliculo-stellate cells that produce various local signaling molecules. The TtT/GF cell line is derived from pituitary tumors, produces no hormones and has folliculo-stellate cell-like characteristics. The biological function of TtT/GF cells remains elusive but several properties have been postulated (support of endocrine cells, control of cell proliferation, scavenger function). Recently, we observed that TtT/GF cells have high resistance to the antibiotic G418 and low influx for Hoechst 33342, indicating the presence of ATP-binding cassette (ABC) transporters that efflux multiple drugs, i.e., a property similar to that of stem/progenitor cells. Therefore, we examine TtT/GF cells for the presence of ABC transporters, for the efflux ability of Hoechst 33342 and for those genes characteristic of TtT/GF cells. Real-time polymerase chain reaction (PCR) for ABC transporters demonstrated that Abcb1a, Abcb1b and Abcg2, regarded as stem cell markers, were characteristically expressed in TtT/GF cells but not in Tpit/F1 and LβT2 cells. Furthermore, the remarkable low-efflux ability of Hoechst 33342 from TtT/GF cells was confirmed by using inhibitors and contrasted with the abilities of Tpit/F1 and LβT2 cells. The high and specific expression of stem cell antigen 1 (Sca1) in TtT/GF cells was confirmed by real-time PCR. We also demonstrated those genes that are expressed abundantly and characteristically in TtT/GF, suggesting that TtT/GF cells have unique characteristics similar to those of stem/progenitor cells of endothelial or mesenchymal origin. Thus, the present study has revealed an intriguing property of TtT/GF cells, providing a new clue for an understanding of the function of this cell line.

  4. Is IGSF1 involved in human pituitary tumor formation?

    Science.gov (United States)

    Faucz, Fabio R; Horvath, Anelia D; Azevedo, Monalisa F; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R; Wit, Jan M; Bernard, Daniel J; Stratakis, Constantine A

    2015-02-01

    IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation.

  5. Is IGSF1 involved in human pituitary tumor formation?

    Science.gov (United States)

    Faucz, Fabio R.; Horvath, Anelia D.; Azevedo, Monalisa F.; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D.; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R.; Wit, Jan M.; Bernard, Daniel J.; Stratakis, Constantine A.

    2014-01-01

    IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in sections from GH-producing adenomas, familial somatomammotroph hyperplasia and in normal pituitary. In two male patients, and in one female, with somatomammotroph hyperplasia from the same family, we identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function. Of 60 female controls, two carried the same variant, and seven were heterozygous for other variants. Immunohistochemistry showed increase IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared to a GH-producing adenoma from a patient negative for any IGSF1 variants and to normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. PMID:25527509

  6. RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors

    Science.gov (United States)

    Zhang, He-Yu; Jin, Long; Stilling, Gail A.; Ruebel, Katharina H.; Coonse, Kendra; Tanizaki, Yoshinori; Raz, Avraham

    2010-01-01

    Galectin-3 is expressed in a cell-type specific manner in human pituitary tumors and may have a role in pituitary tumor development. In this study, we hypothesized that Galectin-3 is regulated by RUNX proteins in pituitary tumors. Transcription factor prediction programs revealed several putative binding sites in the LGALS3 (Galectin-3 gene) promoter region. A human pituitary cell line HP75 was used as a model to study LGALS3 and RUNX interactions using Chromatin immunoprecipitation assay and electrophoresis mobility shift assay. Two binding sites for RUNX1 and one binding site for RUNX2 were identified in the LGALS3 promoter region. LGALS3 promoter was further cloned into a luciferase reporter, and the experiments showed that both RUNX1 and RUNX2 upregulated LGALS3. Knock-down of either RUNX1 or RUNX2 by siRNA resulted in a significant downregulation of Galectin-3 expression and decreased cell proliferation in the HP 75 cell line. Immunohistochemistry showed a close correlation between Galectin-3 expression and RUNX1/RUNX2 level in pituitary tumors. These results demonstrate a novel binding target for RUNX1 and RUNX2 proteins and suggest that Galectin-3 is regulated by RUNX1 and RUNX2 in human pituitary tumor cells by direct binding to the promoter region of LGALS3 and thus may contribute to pituitary tumor progression. PMID:19020999

  7. RNAi-mediated knockdown of pituitary tumor-transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, S.Q. [Department of Urology and Center of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing (China); Institute of Urology, Peking University and Department of Urology, First Hospital, Peking University, Beijing (China); Liao, Q.J.; Wang, X.W. [Department of Urology and Center of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing (China); Xin, D.Q. [Institute of Urology, Peking University and Department of Urology, First Hospital, Peking University, Beijing (China); Chen, S.X.; Wu, Q.J.; Ye, G. [Department of Urology and Center of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing (China)

    2012-08-10

    Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.

  8. Pregnancy in patients with pituitary tumors.

    Science.gov (United States)

    Husami, N; Jewelewicz, R; Vande Wiele, R L

    1977-09-01

    Thirteen patients with pituitary tumors had a total of seventeen pregnancies. Nine of these patients were treated prior to conception (four by radiation therapy, four by hypophysectomy, and one with lergotrile); four patients received no treatment. The untreated group had a total of six pregnancies, two of which were complicated by visual symptoms which regressed spontaneously after delivery. One of the hypophysectomized patients developed diabetes insipidus at 34 weeks' gestation which resolved spontaneously after delivery. Of the four irradiated patients, one had a child with Down's syndrome and another had a child with multiple congenital anomalies who died. The clinical course and various modes of treatment of these patients are discussed and the pertinent literature is reviewed.

  9. Gamma knife radiosurgery for secreting pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Noren, G. [Brown Univ., Providence, RI (United States). Rhode Island Hospital; Jackson, I.M.D.; Chougule, P.; Zheng, Z.; Epstein, M.H.

    1998-09-01

    Transsphenoidal surgery usually represents first line treatment for pituitary adenomas with the aim of removing the tumor, decompressing the optic apparatus and, in secreting tumors, eliminating the hypersecretion. Gamma Knife radiosurgery is indicated for tumor remnants or recurrences in or above the sella including those invading the cavernous sinus and also as initial treatment in patients who are unable to tolerate an open surgical procedure and where medication has failed. In this study, the target definition was retrospectively studied and when necessary corrected in 10 acromegalic patients, 8 with Cushing`s disease, and 12 with prolactinomas undergoing Gamma Knife radiosurgery. The dose plan was analyzed and the volume of the target covered by a minimum of 15, 20, 25, 30 and 35 Gy was estimated. A dose/volume profile for each treatment was created and correlated to the endocrinological and clinical outcome. Cure, according to strict endocrinological criteria, was seen in 6 of the acromegalic patients, in 2 of the patients with ACTH hypersecretion, and in 2 of the patients with prolactinomas. Analysis of these profiles, also for the patients with partial effect, show that a minimum radiation dose of 20 Gy may be adequate to eliminate the hypersecretion in acromegalic patients whereas a dose of at least 25 Gy may be required in patients with Cushing`s disease and prolactinoma. (author)

  10. Sudden and unexpected death from pituitary tumor apoplexy.

    Science.gov (United States)

    Shields, Lisa B E; Balko, M Gregory; Hunsaker, John C

    2012-01-01

    Pituitary tumor apoplexy refers to a clinical syndrome precipitated by the expansion of a pituitary adenoma by hemorrhage or infarction. Individuals may present with myriad signs, including sudden onset of severe headache, visual changes, altered mental status, cranial nerve palsies, and hormonal dysfunction. This disorder constitutes a medical emergency and warrants an expedited evaluation, diagnosis, and treatment to prevent the potential sequelae of permanent visual loss, endocrine abnormalities, or death. We report a case of sudden death from undiagnosed pituitary tumor apoplexy. The decedent was evaluated by medical personnel on three occasions in the week prior to her death for severe headache, nausea, vomiting, and photophobia. Postmortem examination demonstrated a hemorrhagic infarction of a pituitary adenoma with necrosis and expansion out of the sella turcica. The recognition of and treatment for a patient with pituitary tumor apoplexy requires a rapid multidisciplinary effort. Failure of prompt diagnosis may be fatal and require a medico-legal death investigation for sudden and unexpected death.

  11. Coexisting intracranial tumors with pituitary adenomas: Genetic association or coincidence?

    Directory of Open Access Journals (Sweden)

    Furtado Sunil

    2010-01-01

    Full Text Available The co-occurrence of two or more brain tumors with different histological features is rare. The authors report three rare cases of intracranial tumors associated with pituitary adenomas. Two of the pituitary tumors were functioning adenomas: a prolactinoma and a thyrotropin secreting adenoma. Two of the associated intracranial neoplasms were gliomas and one was a meningioma. Radiological and clinical examination for syndromal association was negative in all cases. We briefly discuss the presentation and treatment options of these cases and review the 19 previous publications in the literature of pituitary tumors occurring in association with other neoplasms and explore the possible links underlying these co-occurring neoplasms. Our three cases represent 0.86% of all pituitary tumors operated at our institute over a 9-year period.

  12. Aspergillosis of the sphenoid sinus simulating a pituitary tumor

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    Larranaga, J.; Fandino, J.; Gomez-Bueno, J.; Botana, C.; Rodriguez, D.; Gonzalez-Carrero, J.

    1989-09-01

    Sphenoidal aspergillosis is an unusual cause of sella turcica enlargement. Pituitary abscess secondary to Aspergillus had been reported. In the present case, a woman with sphenoid sinus aspergillosis mimiced a pituitary tumor. This patient survived her infection with intact pituitary function following a transsphenoidal approach. No postoperative amphotericine-B and 5-fluorocytosine were necessary. CT scan revealed a mass occupying the sphenoid sinus extending to the sella turcica. Factors that should alert the clinican to the presence of a sphenoidal and pituitary abscess in a patient with sella turcica enlargement are prior episodes of sinusitis, meningitis and immunosuppression and, as in the present case, hyperglycemia. (orig.).

  13. The molecular pathogenesis of pituitary tumors: implications for clinical management.

    Science.gov (United States)

    Dworakowska, D; Grossman, A B

    2012-06-01

    Pituitary adenomas are unique in several ways, and while they are rarely malignant they may be invasive and/or recurrent. Several attempts have been made to determine the growth potential of pituitary adenomas. Pituitary tumors predominantly arise in a sporadic setting or more rarely as part of hereditary genetic syndromes. Molecular analysis of these familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of genes or molecular alterations involved in pituitary tumorigenesis is progressively increasing, providing a hope for development of new predictive and prognostic markers. The aim of this review is to focus on the molecular pathology of pituitary adenomas in the context of their implications on management and targeted therapy. We have summarized our current knowledge on the molecular biology in familial and sporadic pituitary adenomas, and we subsequently focus on prognostic factors as well as specific predictive markers for new promising targeted therapies.

  14. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.

    Science.gov (United States)

    Raverot, Gérald; Sturm, Nathalie; de Fraipont, Florence; Muller, Marie; Salenave, Sylvie; Caron, Philippe; Chabre, Olivier; Chanson, Philippe; Cortet-Rudelli, Christine; Assaker, Richard; Dufour, Henry; Gaillard, Stephan; François, Patrick; Jouanneau, Emmanuel; Passagia, Jean-Guy; Bernier, Michèle; Cornélius, Aurélie; Figarella-Branger, Dominique; Trouillas, Jacqueline; Borson-Chazot, Françoise; Brue, Thierry

    2010-10-01

    To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide. The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression. Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study. MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing. Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients. Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

  15. The role of temozolomide in the treatment of aggressive pituitary tumors.

    Science.gov (United States)

    Liu, James K; Patel, Jimmy; Eloy, Jean Anderson

    2015-06-01

    Pituitary tumors are amongst the most common intracranial neoplasms and are generally benign. However, some pituitary tumors exhibit clinically aggressive behavior that is characterized by tumor recurrence and continued progression despite repeated treatments with conventional surgical, radiation and medical therapies. More recently, temozolomide, a second generation oral alkylating agent, has shown therapeutic promise for aggressive pituitary adenomas and carcinomas with favorable clinical and radiographic responses. Temozolomide causes DNA damage by methylation of the O(6) position of guanine, which results in potent cytotoxic DNA adducts and consequently, tumor cell apoptosis. The degree of MGMT expression appears to be inversely related to therapeutic responsiveness to temozolomide with a significant number of temozolomide-sensitive pituitary tumors exhibiting low MGMT expression. The presence of high MGMT expression appears to mitigate the effectiveness of temozolomide and this has been used as a marker in several studies to predict the efficacy of temozolomide. Recent evidence also suggests that mutations in mismatch repair proteins such as MSH6 could render pituitary tumors resistant to temozolomide. In this article, the authors review the development of temozolomide, its biochemistry and interaction with O(6)-methylguanine-DNA methyltransferase (MGMT), its role in adjuvant treatment of aggressive pituitary neoplasms, and future works that could influence the efficacy of temozolomide therapy.

  16. Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

    Directory of Open Access Journals (Sweden)

    Sang Ouk Chin

    2015-09-01

    Full Text Available A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH, prolactin (PRL, and thyroid stimulating hormone (TSH. Staining for pituitary-specific transcription factor-1 (Pit-1 was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.

  17. Resistance to dopamine agonists and somatostatin analogues in pituitary tumors: focus on cytoskeleton involvement

    Directory of Open Access Journals (Sweden)

    Erika ePeverelli

    2015-12-01

    Full Text Available Pituitary tumors, that origin from excessive proliferation of a specific subtype of pituitary cell, are mostly benign tumors, but may cause significant morbidity in affected patients, including visual and neurologic manifestations from mass-effect, or endocrine syndromes caused by hormone hypersecretion. Dopamine (DA receptor DRD2 and somatostatin (SS receptors (SSTRs represent the main targets of pharmacological treatment of pituitary tumors since they mediate inhibitory effects on both hormone secretion and cell proliferation, and their expression is retained by most of these tumors. Although long acting DA and SS analogs are currently used in the treatment of prolactin (PRL- and growth hormone (GH-secreting pituitary tumors, respectively, clinical practice indicates a great variability in the frequency and entity of favourable responses. The molecular basis of the pharmacological resistance are still poorly understood, and several potential molecular mechanisms have been proposed, including defective expression or genetic alterations of DRD2 and SSTRs, or an impaired signal transduction. Recently, a role for cytoskeleton protein filamin A (FLNA in DRD2 and SSTRs receptors expression and signalling in PRL- and GH- secreting tumors, respectively, has been demonstrated, first revealing a link between FLNA expression and responsiveness of pituitary tumors to pharmacological therapy. This review provides an overview of the known molecular events involved in SS and DA resistance, focusing on the role played by FLNA.

  18. What Happens After Treatment for Pituitary Tumors?

    Science.gov (United States)

    ... develop pituitary hormone deficiencies after surgery or radiation therapy. These people will need hormone replacement. Thyroid hormone and adrenal steroids can be taken as pills. In men, testosterone can be given to restore sex drive and ...

  19. Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor

    Science.gov (United States)

    Liu, Ning-Ai; Jiang, Hong; Ben-Shlomo, Anat; Wawrowsky, Kolja; Fan, Xue-Mo; Lin, Shuo; Melmed, Shlomo

    2011-01-01

    Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective pituitary targeted pharmacotherapy for Cushing disease. Here, we generated germline transgenic zebrafish with overexpression of pituitary tumor transforming gene (PTTG/securin) targeted to the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features pathognomonic of corticotroph adenomas, including corticotroph expansion and partial glucocorticoid resistance. Adult Tg:Pomc-Pttg fish develop neoplastic coticotrophs and pituitary cyclin E up-regulation, as well as metabolic disturbances mimicking hypercortisolism caused by Cushing disease. Early development of corticotroph pathologies in Tg:Pomc-Pttg embryos facilitated drug testing in vivo. We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos. We further validated that orally administered R-roscovitine suppresses ACTH and corticosterone levels, and also restrained tumor growth in a mouse model of ACTH-secreting pituitary adenomas. Molecular analyses in vitro and in vivo showed that R-roscovitine suppresses ACTH expression, induces corticotroph tumor cell senescence and cell cycle exit by up-regulating p27, p21 and p57, and downregulates cyclin E expression. The results suggest that use of selective CDK inhibitors could effectively target corticotroph tumor growth and hormone secretion. PMID:21536883

  20. Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells.

    Science.gov (United States)

    Wozniak, Ann L; Bulayeva, Nataliya N; Watson, Cheryl S

    2005-04-01

    Xenoestrogens (XEs) are widespread in our environment and are known to have deleterious effects in animal (and perhaps human) populations. Acting as inappropriate estrogens, XEs are thought to interfere with endogenous estrogens such as estradiol (E2) to disrupt normal estrogenic signaling. We investigated the effects of E2 versus several XEs representing organochlorine pesticides (dieldrin, endosulfan, o',p'-dichlorodiphenylethylene), plastics manufacturing by-products/detergents (nonylphenol, bisphenol A), a phytoestrogen (coumestrol), and a synthetic estrogen (diethylstilbestrol) on the pituitary tumor cell subline GH3/B6/F10, previously selected for expression of high levels of membrane estrogen receptor-alpha. Picomolar to nanomolar concentrations of both E2 and XEs caused intracellular Ca2+ changes within 30 sec of administration. Each XE produced a unique temporal pattern of Ca2+ elevation. Removing Ca2+ from the extracellular solution abolished both spontaneous and XE-induced intracellular Ca2+ changes, as did 10 microM nifedipine. This suggests that XEs mediate their actions via voltage-dependent L-type Ca2+ channels in the plasma membrane. None of the Ca2+ fluxes came from intracellular Ca2+ stores. E2 and each XE also caused unique time- and concentration-dependent patterns of prolactin (PRL) secretion that were largely complete within 3 min of administration. PRL secretion was also blocked by nifedipine, demonstrating a correlation between Ca2+ influx and PRL secretion. These data indicate that at very low concentrations, XEs mediate membrane-initiated intracellular CCa2+ increases resulting in PRL secretion via a mechanism similar to that for E2, but with distinct patterns and potencies that could explain their abilities to disrupt endocrine functions.

  1. The pituitary growth hormone cell in space

    Science.gov (United States)

    Hymer, Wesley C.; Grindeland, R.

    1989-01-01

    Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

  2. Quantitative evaluation of indium-111 (In-111) octreotide pituitary activity: Comparison in patient with and without pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, P.; Waxman, A.; Nguyen, K. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

    1995-05-01

    Indium 111 Octreotide is known to detect pituitary tumors. Variable low level pituitary activity has been reported in pts. with no demonstrable pituitary tumors. To our knowledge, there have been no studies which quantitatively categorize pituitary activity with respect to distinguishing normal subject from pts. with pituitary tumors. 13 pts. with proven, treated acromegaly were included, as well as 15 pts. with no history of pituitary disorder. Both groups underwent SPECT In-111 scintigraphy 24 hours post-injection Average count per pixel ratios were obtained for the pituitary/calvarium (P/C) and pituitary/brain (P/B) regions. 10 pts. with acromegaly underwent growth hormone (GH) measurements 2 hours post-glucose load. Statistical correlation between growth hormone levels using P/C and P/B ratios were obtained. P/C ratios, as well as P/B ratios demonstrated high correlation with serum GH levels correlation coefficient(r)= .717 for P/C p<0.05, and correlation coefficient(r) = 0.828 for P/B ratios p<0.005. P/C ratios and P/B ratios for controls correlated closely with the upper level of normal predicted by P/C or P/B ratios as a function of serum growth hormone found in patients with acromegaly. Somatostatin receptor SPECT scintigraphy of the pituitary and appropriate quantitation can predict patients with growth hormone secreting tumors.

  3. Components of the canonical and non-canonical Wnt pathways are not mis-expressed in pituitary tumors.

    Directory of Open Access Journals (Sweden)

    Leandro Machado Colli

    Full Text Available INTRODUCTION: Canonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown. OBJECTIVE: This study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome. MATERIALS AND METHODS: Genes of the WNT canonical pathway: activating ligands (WNT11, WNT4, WNT5A, binding inhibitors (DKK3, sFRP1, β-catenin (CTNNB1, β-catenin degradation complex (APC, AXIN1, GSK3β, inhibitor of β-catenin degradation complex (AKT1, sequester of β-catenin (CDH1, pathway effectors (TCF7, MAPK8, NFAT5, pathway mediators (DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1, target genes (MYB, MYC, WISP2, SPRY1, TP53, CCND1; calcium dependent pathway (PLCB1, CAMK2A, PRKCA, CHP; and planar cell polarity pathway (PTK7, DAAM1, RHOA were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin, planar cell polarity (JNK, and calcium dependent (NFAT5 Wnt pathways were evaluated by immunohistochemistry. RESULTS: There are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for WISP2, which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02, NS pituitary tumors (7.7x; p = 0.004 and GH-secreting tumors (5.0x; p = 0.05. β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram. CONCLUSIONS: Our data reinforce previous reports

  4. Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressing MYCN in hGFAP-positive cells

    NARCIS (Netherlands)

    Fielitz, K. (Kathrin); Althoff, K. (Kristina); De Preter, K. (Katleen); J. Nonnekens (Julie); Ohli, J. (Jasmin); Elges, S. (Sandra); Hartmann, W. (Wolfgang); G. Kloppel (Günter); Knösel, T. (Thomas); Schulte, M. (Marc); L. Klein-Hitpass (Ludger); Beisser, D. (Daniela); Reis, H. (Henning); Eyking, A. (Annette); Cario, E. (Elke); J.H. Schulte (Johannes); A. Schramm (Alexander); U. Schüller (Ulrich)

    2016-01-01

    textabstractAmplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the s

  5. The value of radiation therapy for pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Watari, Tsutomu [Dokkyo Univ., Mibu, Tochigi (Japan). School of Medicine

    1995-09-01

    Following points are discussed in this review. (1) Historical review of our previous therapeutic management. (2) Classification of pituitary adenomas. (3) Clinical analysis of my recent 58 cases. (4) Verification of usefulness of postoperative irradiation which achieved to increase in local control rate. (5) Authoritativeness of radiotherapy. In general, 3 to 4 portal technique or arc therapy were employed. The lateral opposing field technique was avoid to use. The recommended doses using linear accelerator x-ray technique is approximately 5000 cGy in 5 weeks. To prevent radiation hazard; (1) examiner should not use technique of two opposed fields, (2) total doses should not exceed 5000 cGy in 5 to 6 weeks and the use of daily fractions should not exceed 200 cGy. (6) Correlation of hormone secreting tumors and radiation therapy. (7) Problem of radiosurgery and heavy particle. (8) Countermeasure for recurrence cases. (9) Problem of side effects of radiotherapy and its precaution. Complication of radiation for pituitary adenoma found that the significant side effects are negligibly small in recent years. (10) Pituitary tumor are originally slow growing and benign tumor, therefore the response to irradiation takes long time to elapse for final evaluation. For instance, over 80 to 90% of acromegaly patients respond HGH successfully, but this may require from one to several years. (11) Conclusion. (author).

  6. The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b)

    NARCIS (Netherlands)

    A. Binnerts (Arjen); P. Uitterlinden (Piet); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven)

    1990-01-01

    markdownabstractAbstract The direct effects of human GH and IGF-I on PRL secretion and cell proliferation were studied on PRL secreting rat pituitary tumor 7315b cells in vitro, as well as the effects in vivo of human GH administration on body weight, IGF-I levels and tumor size in rats bearing th

  7. Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion.

    Science.gov (United States)

    Vazquez-Martinez, Rafael; Martinez-Fuentes, Antonio J; Pulido, Marina R; Jimenez-Reina, Luis; Quintero, Ana; Leal-Cerro, Alfonso; Soto, Alfonso; Webb, Susan M; Sucunza, Nuria; Bartumeus, Frederic; Benito-Lopez, Pedro; Galvez-Moreno, Maria A; Castaño, Justo P; Malagon, Maria M

    2008-06-01

    Rab proteins regulate the sequential steps of intracellular membrane transport. Alterations of these GTPases and their associated proteins are emerging as the underlying cause for several human diseases involving dysregulated secretory activities. Herein we investigated the role of Rab18, which negatively regulates hormone secretion by interacting with secretory granules, in relation to the altered functioning of tumoral pituitary somatotropes causing acromegaly. A total of 18 patients diagnosed with pituitary tumors causing acromegaly (nine patients) or nonfunctioning adenomas (nine patients) underwent endoscopic transsphenoidal surgery. Adenomas were subsequently processed to evaluate Rab18 production in relation to GH secretion. We found that somatotropinoma cells are characterized by a high secretory activity concomitantly with a remarkably reduced Rab18 expression (15%) and protein content levels (30%), as compared with cells from nonfunctioning pituitary adenomas derived from patients with normal or reduced GH plasma levels (100%). Furthermore, immunoelectron microscopy revealed that Rab18 association with the surface of GH-containing secretory granules was significantly lower in somatotropes from acromegalies than nonfunctioning pituitary adenomas. Finally, we provide evidence that modulation of Rab18 gene expression can revert substantially the hypersecretory activity of cells because Rab18 overexpression reduced by 40% the capacity of cells from acromegalies to respond to GHRH stimulation. These results suggest that molecular alterations affecting individual components of the secretory granule traffic machinery can contribute to maintain a high level of GH in plasma. Accordingly, Rab18 constitutes a valuable target as a diagnostic, prognostic, and/or therapeutic tool for human acromegaly.

  8. Silencing of HOTAIR expression inhibits the temozolomide-induced apoptosis in pituitary tumor cells%抑制 HOTAIR 的表达促进替莫唑胺引起的垂体腺瘤细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    李九州; 张玉奇; 赵全成; 刘洪恩; 左凯

    2016-01-01

    目的:探索长链非编码RNA(long noncoding RNA ,lncRNA)HOTAIR在替莫唑胺引起的垂体瘤细胞凋亡中的功能。方法体外培养垂体腺瘤细胞系 HP75细胞和GH3细胞,使用替莫唑胺处理 HP75细胞和GH3细胞后,采用实时定量PCR法检测细胞中 HOTAIR的表达;采用RNA干扰(RNA interference ,RNAi)技术敲低内源性 HOTAIR的表达;并应用MTT法检测敲低内源性HOTAIR后细胞增殖能力的改变,应用流式细胞术检测敲低内源性 HOTAIR后替莫唑胺对垂体腺瘤细胞凋亡的影响。结果替莫唑胺能够引起垂体腺瘤HP75细胞和GH3细胞显著的凋亡,并且在此过程中HOTAIR的表达显著降低;采用RNAi技术能够显著地抑制垂体腺瘤细胞系中HOTAIR的表达;敲低HOTAIR后,细胞的增殖能力受到明显的抑制,如果同时使用替莫唑胺处理细胞,细胞的凋亡率出现显著地升高。结论敲低内源性 HOTAIR的表达能够促进替莫唑胺引起的垂体腺瘤细胞凋亡,二者具有协同作用。%Objective To investigate the effect of long non-coding RNA (lncRNA) HOTAIR on the temozolomide-induced apoptosis of pituitary tumor cells .Methods Pituitary adenoma cell line HP75 cells and GH3 cells were cultured in vitro ,quanti-tative real-time PCR was used to detect the expression level of lncRNA HOTAIR in HP75 cells and GH3 cells after treatment with temozolomide .The HP75 cells and GH3 cells were transfected with siRNA specially targeting HOTAIR to knock endoge-nous HOTAIR down in vitro ;furthermore ,MTT assay was used to detect the proliferation rate in HP75 and GH3 cells ,flow cytometry assay was employed to detect the temozolomide-induced apoptosis in HP75 cells and GH3 cells .Results Temozolo-mide could cause significant apoptosis in pituitary tumor HP75 cells GH3 cells ,at the same time ,the expression of HOTAIR was significantly reduced in cells treated with temozolomide;the expression of HOTAIR could be

  9. A 23-Year-Old Female with a Mixed Germ Cell Tumor of the Pituitary Infundibulum: The Challenge of Differentiating Neoplasm from Lymphocytic Infundibuloneurohypophysitis—A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sann Yu Mon

    2014-01-01

    Full Text Available The pathologic spectrum of diseases that infiltrate the pituitary infundibulum includes a broad variety of clinical entities. There are significant differences in the prevalence of these etiologies depending on the age of presentation. Lymphocytic infundibuloneurohypophysitis (LINH predominates over other causes of infundibular disease in adults over age 21. Differentiating LINH from other causes of infundibular disease can be difficult because the various etiologies often have similar clinical presentations and radiologic imaging characteristics. We report the first case in an adult of a mixed germ cell tumor comprised of germinoma and embryonal cell carcinoma infiltrating the pituitary infundibulum. In our case, a 23-year-old female was initially misdiagnosed as having LINH. She presented with panhypopituitarism and diabetes insipidus, which is the most common initial presentation in both entities. The two diagnoses are difficult to distinguish based on MRI imaging, CSF findings, and histopathological examination. Our case demonstrates the need for close follow-up of patients with isolated lesions of the pituitary infundibulum and reinforces the need for biopsy of an infundibular lesion when progression of disease is demonstrated. In our case, biopsy with comprehensive immunohistochemical staining was the sole means of making a definitive diagnosis.

  10. Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression.

    Science.gov (United States)

    Zhao, Yachao; Xiao, Zheng; Chen, Wenna; Yang, Jinsheng; Li, Tao; Fan, Bo

    2015-08-01

    O6-methylguanine-DNA methyltransferase (MGMT) activity is responsible for temozolomide (TMZ) resistance in patients harboring aggressive pituitary adenomas. Recently, disulfiram (DSF) has been shown to induce the loss of MGMT protein and increase TMZ efficacy in glioblastoma cells, while CD133+ nestin+ cells isolated from the cell population have been implicated as pituitary adenoma stem-like cells. However, whether DSF is able to potentiate the cytotoxic effects of TMZ on human pituitary adenoma cells has not been investigated to date. In the present study, CD133+ nestin+ phenotype cells were isolated from primary cultured human pituitary adenoma cells using microbeads. It was found that DSF reduced MGMT protein expression and sensitized human pituitary adenoma cells and stem-like cells to TMZ in vitro, while the proteasome inhibitor PS-341 abrogated the inhibitory effect of DSF on MGMT in vitro. The sensitizing effect of DSF was also verified in primary cultured human pituitary adenoma cells in vivo. The results of the present study suggested that DSF can increase the efficacy of the anti-tumor effect of TMZ on human pituitary adenoma cells and CD133+ nestin+ stem like cells via the ubiquitin-proteasomal MGMT protein elimination route. DSF combined with TMZ may be an effective therapeutic strategy against aggressive pituitary adenomas.

  11. Hyperprolactinemia in nonpregnant women due to pituitary tumors.

    Science.gov (United States)

    Tolstoi, L G

    1986-06-02

    The human prolactin molecule has been isolated and its structure characterized. This anterior pituitary hormone plays an important function in the induction and maintenance of lactation in the post-partum nursing mother. Prolactin-producing tumors cause inappropriate lactation in the nonpregnant woman. Bromocriptine, an ergot derivative, mimics the action of dopamine in the anterior pituitary gland and does not cure the underlying pathology. Prior to the development of bromocriptine, there was no effective treatment for the symptoms of amenorrhea and galactorrhea. Although the methods of therapy are more sophisticated today, there remain a number of unanswered questions. The unknown long-term risks of bromocriptine therapy must be balanced against the potential risk of osteopenia.

  12. Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

    Directory of Open Access Journals (Sweden)

    M. Paez-Pereda

    2005-10-01

    Full Text Available The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

  13. [Pituitary tumors: 10 years of experience].

    Science.gov (United States)

    Cecenarro, Laura Anahi; Rodrigo Fanton, Elica Tatiana; Estario, Paula; Papalini, Roque Francisco; Estario, María Éugenia

    2015-01-01

    Introducción: Los tumores hipofisarios comprenden la cuarta parte de las neoplasias intracraneales y los adenomas son el mayor porcentaje de ellos. Son de naturaleza benigna, pero pueden ser invasivos y producir impacto en la morbi-mortalidad. Objetivo: analizar las características clínicas de los pacientes con diagnóstico de adenomas hipofisarios y crear un registro computarizado para mejorar las estrategias de diagnóstico y seguimiento de estos pacientes. Metodología: Se realizó un análisis retrospectivo, descriptivo, de 102 historias clínicas sobre un total de 191 pacientes que concurrieron al servicio de endocrinología desde el año 2003 al 2014 . Las variables fueron analizadas mediante las correspondientes estadísticas descriptivas. Se utilizó el programa SPSS 11.5. Resultados: El 63% fueron mujeres, y el mayor porcentaje etario entre 25-60 años (74.4%). El 54% correspondió a adenomas no funcionantes, el 28% a prolactinomas, el 11.8% somatotropinomas y el 6.2% corticotropinomas. En todos los tipos el grupo femenino fue mayoritario, excepto en los no funcionantes. De los adenomas no funcionantes el 79% fueron macroadenomas, los prolactinomas el 52% fueron microadenomas y se realizó cirugía en el 37% de ellos. Los somatotropinomas, en el 80% fueron macroadenomas, se operó el 80% de los pacientes y radioterapia al 40%. En los corticotropinomas, tanto micro como macroadenomas se presentaron en igual porcentaje (50%) y todos ellos recibieron tratamiento quirúrgico. Conclusión: Los hallazgos coinciden con la literatura en cuanto a frecuencia y edad de presentación de los adenomas. Consideramos valioso la elaboración de un registro que nos permita optimizar el seguimiento y tratamiento de los pacientes, la investigación y divulgación científica.

  14. Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report

    Science.gov (United States)

    Wendel, Chloé; Campitiello, Marco; Plastino, Francesca; Eid, Nada; Hennequin, Laurent; Quétin, Philippe; Longo, Raffaele

    2017-01-01

    Patient: Male, 61 Final Diagnosis: Pituitary metastasis from renal cell carcinoma Symptoms: Deterioration of visual acuity and field • persisting headache • excess thirst • polyuria Medication: — Clinical Procedure: Total body CT-scan • brain MRI • trans-sphenoidal endoscopical surgery • radiotherapy • anti-angiogenic therapy Specialty: Oncology Objective: Rare disease Background: Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. Case Report: We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus. Brain MRI revealed a large sellar tumor lesion bilaterally infiltrating the cavernous sinuses, which was surgically resected. Histology confirmed a ccRCC pituitary metastasis. The patient received post-surgical radiotherapy. Considering the presence of concomitant extra-pituitary metastases, treatment with sunitinib was started, followed by several lines of therapy with axitinib, everolimus, and sorafenib because of tumor progression. The patient also presented with a pituitary tumor recurrence, which was treated by stereotaxic radiotherapy. He died five years after the initial diagnosis of RCC and 30 months after the diagnosis of the pituitary metastasis. Conclusions: There are no standardized treatment guidelines for management of pituitary metastases. Pituitary surgery plays a role in symptom palliation, and it does not have any relevant impact on survival. Exclusive radiotherapy or stereotaxic radiotherapy could be an alternative to surgery in patients whose general condition is poor or who have concomitant extra-pituitary metastases. PMID:28044054

  15. Hepatocellular carcinoma metastasis to the brain mimicking primary pituitary tumor around the sella turcica.

    Science.gov (United States)

    Tamura, Tetsuo; Kawamura, Yusuke; Ikeda, Kenji; Seko, Yuya; Fukushima, Taito; Kumada, Hiromitu; Yamada, Shozo; Matumaru, Yuji

    2013-08-01

    We report on two cases of hepatocellular carcinoma (HCC) with metastasis to the cavernous sinus and sphenoid sinus. Both cases presented with diplopia and retro-orbital headache and both underwent surgery for a primary pituitary gland tumor. After surgery, both cases were diagnosed with metastases from HCC. Case 1 was a 67-year-old male with a history of HCC who was referred to our hospital for pituitary tumor surgery. The tumor appeared to be in the sella turcica and to invade the sphenoid sinus and right cavernous sinus. Transnasal transsphenoidal surgery (TSS) was performed. The tumor was postoperatively diagnosed by histology to be a metastatic pituitary tumor from HCC. Radiotherapy was administered to the metastatic site. Case 2 was a 58-year-old male with a history of TSS for a pituitary tumor 16 years previously. He was referred to our hospital for TSS for a recurrent pituitary adenoma. TSS was performed twice in 3 months. During a preoperative general examination, HCC and chronic hepatitis B were revealed. TSS was performed initially, followed by arterial infusion chemotherapy. After TSS, the pituitary tumor was diagnosed by histology to be a metastasis from HCC. As with Case 1, radiotherapy was administered to the metastasis. Most tumors in the sella turcica are pituitary adenomas, although some cases of metastatic pituitary tumors and skull base metastases have been reported. Distant metastases generally have a poor prognosis; however, surgery to the metastatic site can effectively control symptoms caused by the metastatic tumor.

  16. Study on the clinical relativity of glial cell growth factor and prolactin pituitary tumor%胶质细胞生长因子与泌乳素垂体瘤的临床相关性研究

    Institute of Scientific and Technical Information of China (English)

    刘永军; 高翔; 刘吉祥; 李建华

    2014-01-01

    目的:探讨胶质细胞生长因子(GGF)与泌乳素垂体瘤临床的相关性,并分析其预测临床复发的价值。方法研究对象为本院收治的71例泌乳素垂体瘤(PRL )患者,采用免疫组织化学检测GGF在肿瘤组织中的表达情况,分析GGF表达水平与PRL水平、肿瘤大小、微血管密度(MVD)及肿瘤侵袭性的关系,并进一步分析GGF表达水平与泌乳素垂体腺瘤复发的临床联系,最后采用多因素Cox生存风险模型寻求可能的预后影响因素。结果不同PRL水平、肿瘤大小、M VD及肿瘤侵袭性的患者其GGF表达水平也具有明显差异,且差异有统计学意义(P<0.05);3年无复发生存分析显示,GGF高表达组患者的3年无复发生存率(71.4%)和生存期(28.0±2.2)个月均明显低于低表达GGF组88.9%和(32.8±1.5)个月,但差异无统计学意义(P>0.05);多因素Cox生存风险模型分析提示GGF可能是预测泌乳素垂体瘤患者复发预后的独立生物学指标( P<0.05)。结论 GGF与泌乳素垂体瘤患者临床基线资料密切相关,且可能成为预测患者复发预后的重要生物学指标。%Objective To explore clinical relevance of the glial cell growth factor (GGF) and pro‐lactin pituitary tumor ,and to analyze clinical value of its predicting recurrence .Methods Research ob‐ject for the records of 71 cases in our hospital ,prolactin (PRL ) of pituitary adenoma patients using immunohistochemical detection GGF expression in tumor tissue ,analysis GGF expression level and the level of PRL ,tumor size ,microvascular density (MVD) and the relationship between tumor invasive , and further analysis GGF expression level and prolactin pituitary adenoma recurrence of clinical rela‐tion ,finally using multiariable Cox survival risk model for possible prognostic factors .Results The dif‐ferent levels of PRL ,tumor size ,tumor MVD and expression level

  17. Regulation of pituitary cell function by adiponectin.

    Science.gov (United States)

    Rodriguez-Pacheco, Francisca; Martinez-Fuentes, Antonio J; Tovar, Sulay; Pinilla, Leonor; Tena-Sempere, Manuel; Dieguez, Carlos; Castaño, Justo P; Malagon, María M

    2007-01-01

    Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.

  18. Single or group housing altered hormonal physiology and affected pituitary and interstitial cell kinetics

    Science.gov (United States)

    A significant negative correlation between testicular interstitial cell tumors and pituitary tumors in control male F344 rats has been reported associated with the number of animals per cage. Change in numbers of animals per cage may cause stress and increased serum corticosteroi...

  19. TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway.

    Science.gov (United States)

    Gao, Feng; Pan, Suxia; Liu, Bing; Zhang, Huanzhi

    2015-01-01

    Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P TFF3, the apoptotic ration was significantly elevated (P TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway.

  20. TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway

    Science.gov (United States)

    Gao, Feng; Pan, Suxia; Liu, Bing; Zhang, Huanzhi

    2015-01-01

    Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P TFF3, the apoptotic ration was significantly elevated (P TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway. PMID:26823779

  1. Clinical and Biochemical Characteristics of Growth Hormone-Secreting Pituitary Tumors

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the difference of biochemical characteristics on gsp-positive and gsp-negative growth hormone (GH)-secreting pituitary tumors, 18 GH-secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp- positive and gsp-negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp-positive patients were higher than those in gsp-negative patients (P<0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp-positive and gsp-negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp-positive with gsp-negative GH-secreting pituitary tumors.

  2. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

    Science.gov (United States)

    Lasolle, Hélène; Cortet, Christine; Castinetti, Fréderic; Cloix, Lucie; Caron, Philippe; Delemer, Brigitte; Desailloud, Rachel; Jublanc, Christel; Lebrun-Frenay, Christine; Sadoul, Jean-Louis; Taillandier, Luc; Batisse-Lignier, Marie; Bonnet, Fabrice; Bourcigaux, Nathalie; Bresson, Damien; Chabre, Olivier; Chanson, Philippe; Garcia, Cyril; Haissaguerre, Magalie; Reznik, Yves; Borot, Sophie; Villa, Chiara; Vasiljevic, Alexandre; Gaillard, Stephan; Jouanneau, Emmanuel; Assié, Guillaume; Raverot, Gérald

    2017-06-01

    Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Multicenter retrospective study by members of the French Society of Endocrinology. Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols. © 2017 European Society of Endocrinology.

  3. Pituitary tumor-transforming gene and its binding factor in endocrine cancer.

    Science.gov (United States)

    Smith, Vicki E; Franklyn, Jayne A; McCabe, Christopher J

    2010-12-03

    The pituitary tumor-transforming gene (PTTG1) encodes a multifunctional protein (PTTG) that is overexpressed in numerous tumours, including pituitary, thyroid, breast and ovarian carcinomas. PTTG induces cellular transformation in vitro and tumourigenesis in vivo, and several mechanisms by which PTTG contributes to tumourigenesis have been investigated. Also known as the human securin, PTTG is involved in cell cycle regulation, controlling the segregation of sister chromatids during mitosis. This review outlines current information regarding PTTG structure, expression, regulation and function in the pathogenesis of neoplasia. Recent progress concerning the use of PTTG as a prognostic marker or therapeutic target will be considered. In addition, the PTTG binding factor (PBF), identified through its interaction with PTTG, has also been established as a proto-oncogene that is upregulated in several cancers. Current knowledge regarding PBF is outlined and its role both independently and alongside PTTG in endocrine and related cancers is discussed.

  4. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

    Directory of Open Access Journals (Sweden)

    Brandon A. Miller MD, PhD

    2013-06-01

    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  5. Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

    NARCIS (Netherlands)

    L.J. Hofland (Leo); W.W. de Herder (Wouter); H.A. Visser-Wisselaar (Heleen); C. van Uffelen; M. Waaijers (Marlijn); J. Zuyderwijk; P. Uitterlinden (Piet); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven); J.M. Kros (Johan)

    1997-01-01

    textabstractThe effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7

  6. Submental tracheal intubation for resection of recurrent giant pituitary tumor:a case report

    Institute of Scientific and Technical Information of China (English)

    Zhong Hejiang; Wang Yunling; Yang Tiande

    2011-01-01

    Airway management in the patients who receive transmaxillary approach for resection of giant pituitary tumor presents a clinical challenge to the anesthesiologists. Oral or nasal route for tracheal intubation can interfere with surgical procedures. This report describes submental tracheal intubation for airway management in a patient who underwent resection of recurrent giant pituitary tumor via transmaxillary approach. Submental tracheal intubation is an adaptable and safe alternative technology for airway management during operation.

  7. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

    Science.gov (United States)

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao

    2015-03-01

    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

  8. Childhood feedback pituitary tumor-like proliferation caused by primary hypothyroidism : a case report%儿童原发性甲状腺功能减退继发垂体反馈性瘤样增生1例

    Institute of Scientific and Technical Information of China (English)

    汪霞; 黄建勇

    2013-01-01

    Feedback pituitary tumor hyperplasia refers to the corresponding pituitary hormone cell hyperpla-sia and pituitary augmentation caused by the primary hypofunction of target gland. The incidence of feedback pituitary tumor-like proliferation caused by primary hypothyroidism is the highest,accounting for 33. 3% of all feedback tumor. Children are rare,but due to the involvement of growth and development,and easily misdiagnosed as pituitary adenomas. However,the clinical treatment of the two principles are completely different from each other. This article will report a case of feedback Pituitary tumor-like proliferation. Caused by primary hypothyroidism in recent years in our hospital. The clinical symptoms, laboratory tests, imaging features, diagnosis and treatment and prognosis of this case will be demonstrated in the report.

  9. Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

    Science.gov (United States)

    Tordjman, K; Stern, N; Ouaknine, G; Yossiphov, Y; Razon, N; Nordenskjöld, M; Friedman, E

    1993-09-01

    The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.

  10. Subchronic exposure to phytoestrogens alone and in combination with diethylstilbestrol - pituitary tumor induction in Fischer 344 rats

    Directory of Open Access Journals (Sweden)

    Kaphalia Bhupendra S

    2010-05-01

    Full Text Available Abstract Background Subchronic administration of the potent pharmaceutical estrogen diethylstilbestrol (DES to female Fischer 344 (F344 rats induces growth of large, hemorrhagic pituitaries that progress to tumors. Phytoestrogens (dietary plant estrogens are hypothesized to be potential tumor inhibitors in tissues prone to estrogen-induced cancers, and have been suggested as "safer" estrogen replacements. However, it is unknown if they might themselves establish or exacerbate the growth of estrogen-responsive cancers, such as in pituitary. Methods We implanted rats with silastic capsules containing 5 mg of four different phytoestrogens - either coumestrol, daidzein, genistein, or trans-resveratrol, in the presence or absence of DES. We examined pituitary and other organ weights, blood levels of prolactin (PRL and growth hormone (GH, body weights, and pituitary tissue histology. Results Blood level measurements of the administered phytoestrogens confirmed successful exposure of the animals to high levels of these compounds. By themselves, no phytoestrogen increased pituitary weights or serum PRL levels after 10 weeks of treatment. DES, genistein, and resveratrol increased GH levels during this time. Phytoestrogens neither changed any wet organ weight (uterus, ovary, cervix, liver, and kidney after 10 weeks of treatment, nor reversed the adverse effects of DES on pituitaries, GH and PRL levels, or body weight gain after 8 weeks of co-treatment. However, they did reverse the DES-induced weight increase on the ovary and cervix. Morphometric examination of pituitaries revealed that treatment with DES, either alone or in combination with phytoestrogens, caused gross structural changes that included decreases in tissue cell density, increases in vascularity, and multiple hemorrhagic areas. DES, especially in combination with phytoestrogens, caused the development of larger and more heterogeneous nuclear sizes in pituitary. Conclusions High levels of

  11. The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis

    OpenAIRE

    Toru Tateno; Asa, Sylvia L.; Lei Zheng; Thomas Mayr; Axel Ullrich; Shereen Ezzat

    2011-01-01

    Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting eff...

  12. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  13. Case Series Study of Visual Field Defects in Pituitary Gland Tumors

    Directory of Open Access Journals (Sweden)

    Vallabha K

    2017-01-01

    Full Text Available Background: The pituitary gland is a small endocrine gland, weighing about 500 mg. Pituitary adenomas account for 12-15 % of all intracranial tumors. Pituitary gland is in the sella turcica, 8-13 mm lower than the optic chiasm. Therefore, when it increases, it can easily compress the optic nerve fibers in the chiasm. Micro adenomas can have a negligible effect on the visual system or on the function impairment when pituitary adenoma compresses the frontal part of optic nerve; impairments in visual fields, visual acuity, and color contrast sensitivity are possible. The long standing compression of the chiasm induces primary optic nerve atrophy, which directly impairs visual function. The prevalence of visual field defects in pituitary adenomas varies from 37 to 96% in different studies. Because of its anatomical relationship with optic chiasm, pituitary adenoma typically results in bitemporal hemianopia. However, according to the tumor size and optic chiasmal position, a variety of field defects can be produced by pituitary adenoma and the tumor size is a significant factor in the severity of Visual field defects. Aim: To study the proportion of patients with visual field defects in pituitary adenomas and to study the pattern of visual field defects in pituitary adenomas. Materials and Methods: 7 patients diagnosed with a pituitary adenoma underwent complete ophthalmic and Humphrey’s Perimetry 30-2 visual field test at Department of Ophthalmology, BLDEU’S Shri B M Patil Medical College Hospital, Vijayapura between January 2015 to December 2015. Results: Among the 7 cases in the study, 2 cases were of pituitary micro adenoma constituting 28.5% and the remaining cases (5 cases were pituitary macro adenoma, constituting 71.5%. Visual acuity of 6/6 - 6/12 were observed in 10 (71.4% out of total 14 eyes. Visual field defects were observed in all 6 cases (85.7%. Bilateral temporal hemianopia was observed in the majority (42.8% of cases with field

  14. Long-term follow-up results of combination therapy of surgery and gamma knife on pituitary tumor

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Hidetoshi; Yoshimoto, Takashi; Shirokura, Hideshi [Tohoku Univ., Sendai (Japan). School of Medicine

    1997-01-01

    Usefulness of the combination therapy for invasive pituitary tumor with surgery and gamma knife (GK) was evaluated on 17 cases followed for >2 years. Tumors involved ACTH cell adenoma, GH cell adenoma, mixed GH and PRL, purihormonal adenoma, gonadotrophic cell adenoma, GH cell adenoma and null cell adenoma, which were divided into I and II group since adverse effects by GK on the normal pituitary tissues could be evaluated according to tumor growth and abnormal hormone secretion. Irradiation was carried out to make the marginal dose of around 30 (15-35) Gy and center dose of 25-70 Gy on the gland, and marginal dose of <10 Gy on optic nerve. After GK, follow-up was done by pituitary hormone values, tests for sight and visual field and MRI examination. Hypopituitarism was seen in 67% with 100% remission of Cushing`s disease. MRI revealed that the adenoma changed to fibrosis (type 1) with increasing Gd-enhancement or to cystic necrosis (type 2) without Gd-enhancement. Values for GH, cortisol and ACTH turned to normal ones. Thus the combination therapy was found useful. (K.H.)

  15. Pituitary null cell adenoma in a domestic llama (Lama glama).

    Science.gov (United States)

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  16. mTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma cells to ionizing radiation.

    Science.gov (United States)

    Sukumari-Ramesh, Sangeetha; Singh, Nagendra; Dhandapani, Krishnan M; Vender, John R

    2011-02-23

    Pituitary adenomas are the most frequent brain tumor in adults. Although histologically benign, pituitary tumors cause significant morbidity and mortality. Neurosurgery and medical therapeutics may lessen the morbidity and mortality associated with pituitary tumors; however, these treatments are associated with significant adverse side effects. Thus, an improved understanding of pituitary adenomas at the molecular and cellular level is needed to design novel therapeutic compounds. To assess the effect of mammalian target of rapamycin (mTOR) inhibition on pituitary adenoma cells, rat GH3 or MMQ cells were treated with the clinically useful mTOR inhibitors, rapamycin or RAD001. Cellular proliferation and growth following exposure to mTOR inhibitors or radiation were assessed using biochemical methods. In the present study, we observed basal activation of mTOR, downstream of constitutive Akt signaling, in rat GH3 adenoma cells. Functionally, the mTOR inhibitors, rapamycin and RAD001 (500 pM-5 nM), induced G1 growth arrest within 24 hours, an effect associated with reduced cellular proliferation. Both rapamycin and RAD001 decreased the phosphorylation of mTOR at the serine 2448, a key determinant of mTOR activity. Inhibition of mTOR also radiosensitized GH3 cells such that 2.5 Gy in combination with 500 pM rapamycin or RAD001 reduced cellular viability more effectively than 2.5 or 10 Gy alone. These data may support a possible therapeutic role for mTOR inhibitors in limiting the cellular proliferation and radioresistance of pituitary adenoma cells.

  17. Internalization of the radioiodinated somatostatin analog [125I-Tyr3]octreotide by mouse and human pituitary tumor cells: increase by unlabeled octreotide

    NARCIS (Netherlands)

    L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Waaijers (Marlijn); J. Zuyderwijk; W.A.P. Breeman (Wouter); S.W.J. Lamberts (Steven)

    1995-01-01

    textabstractRecently, we developed a technique that allows the in vivo visualization in man of somatostatin receptor-positive neuroendocrine tumors after i.v. injection of [125I-Tyr3]octreotide or [111In-DTPA-D-Phe1]octreotide. Radiotherapy of such tumors using somatost

  18. Metastatic Mantle Cell Lymphoma to the Pituitary Gland: Case Report and Literature Review

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    Arthur Wang

    2016-01-01

    Full Text Available We present an unusual case of a metastatic mantle cell lymphoma (MCL to the pituitary gland. The patient had a known history of MCL for which she previously received chemotherapy. She presented with new-onset diplopia and confusion, and reported a history of progressive vision blurriness associated with headache, nausea, and vomiting. MRI of the brain showed an enhancing lesion within the sella turcica involving the cavernous sinuses bilaterally, extending into Meckel's cave on the left, and abutting the optic nerves bilaterally. Following surgical excision, histopathology revealed the tumor to be a MCL. Metastatic pituitary tumors are rare and have been estimated to make up 1% of tumors discovered in the sellar region. The two most common secondary metastatic lesions to the sella are breast and lung carcinoma followed by prostate, renal cell, and gastrointestinal carcinoma. Metastatic lymphoma to the pituitary gland is especially rare and is estimated to constitute 0.5% of all metastatic tumors to the sella turcica. To our knowledge, this is the first reported case of MCL metastasizing to the pituitary gland.

  19. Metastatic Mantle Cell Lymphoma to the Pituitary Gland: Case Report and Literature Review

    Science.gov (United States)

    Wang, Arthur; Carberry, Nathan; Solli, Elena; Kleinman, George; Tandon, Adesh

    2016-01-01

    We present an unusual case of a metastatic mantle cell lymphoma (MCL) to the pituitary gland. The patient had a known history of MCL for which she previously received chemotherapy. She presented with new-onset diplopia and confusion, and reported a history of progressive vision blurriness associated with headache, nausea, and vomiting. MRI of the brain showed an enhancing lesion within the sella turcica involving the cavernous sinuses bilaterally, extending into Meckel's cave on the left, and abutting the optic nerves bilaterally. Following surgical excision, histopathology revealed the tumor to be a MCL. Metastatic pituitary tumors are rare and have been estimated to make up 1% of tumors discovered in the sellar region. The two most common secondary metastatic lesions to the sella are breast and lung carcinoma followed by prostate, renal cell, and gastrointestinal carcinoma. Metastatic lymphoma to the pituitary gland is especially rare and is estimated to constitute 0.5% of all metastatic tumors to the sella turcica. To our knowledge, this is the first reported case of MCL metastasizing to the pituitary gland. PMID:26933415

  20. Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis

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    Huang Mu-Chiou

    2007-03-01

    Full Text Available Abstract Background Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma. Results The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine. Conclusion Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.

  1. A GRFa2/Prop1/stem (GPS) cell niche in the pituitary.

    Science.gov (United States)

    Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A; Ryan, Aymee K; Blasco, Maria A; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V

    2009-01-01

    The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as

  2. A GRFa2/Prop1/stem (GPS cell niche in the pituitary.

    Directory of Open Access Journals (Sweden)

    Montse Garcia-Lavandeira

    Full Text Available BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the

  3. 17-beta-estradiol-dependent regulation of somatostatin receptor subtype expression in the 7315b prolactin secreting rat pituitary tumor in vitro and in vivo

    NARCIS (Netherlands)

    H.A. Visser-Wisselaar (Heleen); C.J. van Uffelen; P.M. van Koetsveld (Peter); E.G. Lichtenauer-Kaligis; A.M. Waaijers (Annet); P. Uitterlinden (Piet); D.M. Mooy; S.W.J. Lamberts (Steven); L.J. Hofland (Leo)

    1997-01-01

    textabstractIn the present study, we have investigated the role of estrogens in the regulation of somatostatin receptor subtype (sst) expression in 7315b PRL-secreting rat pituitary tumor cells in vitro and in vivo. sst were undetectable in freshly dispersed cells of the transplant

  4. Ikaros isoforms in human pituitary tumors: distinct localization, histone acetylation, and activation of the 5' fibroblast growth factor receptor-4 promoter.

    Science.gov (United States)

    Ezzat, Shereen; Yu, Shunjiang; Asa, Sylvia L

    2003-09-01

    Targeted expression of a human pituitary tumor derived-fibroblast growth factor receptor-4 (FGFR4) recapitulates pituitary tumorigenesis. We have shown that FGFR4 is a target for Ikaros, a zinc finger-containing transcription factor that localizes to heterochromatin regions and participates in higher order chromatin complexes and control of gene expression. We report here the expression of Ikaros and functional differences between its alternatively spliced variants in human pituitary tumors. Ik1 expression was detected in human pituitary tumors and we also identified a truncated isoform consistent with the non-DNA-binding Ik6 isoform in a subset of adenomas by reverse transcriptase-polymerase chain reaction, sequencing, and Western immunoblotting. Transfection of Ik6 in GH4 pituitary cells resulted in predominantly cytoplasmic expression as compared to Ik1, which resulted in exclusively nuclear expression as determined by immunofluorescence and immunoblotting of fractionated protein. Immunohistochemistry of primary human pituitary adenomas localized Ikaros expression to the nuclear compartment but also in the cytoplasm, the latter consistent with Ik6. Expression of Ikaros and truncated non-DNA-binding isoforms was also suggested by electromobility shift assays using nuclear proteins from primary human pituitary adenomas. Ik6 resulted in reversal of the effects of Ik1 on wild-type 5' FGFR4 promoter activity, histone acetylation, and regulation of the endogenous gene. We conclude that dominant-negative Ik6 isoforms with their distinct localization and effects on Ik1 action may contribute to the altered expression of FGFR4 and possibly other target genes in human pituitary tumors.

  5. Adenomas hipofisários: relação entre invasividade e índice proliferativo tumoral Pituitary adenomas: relationship between invasiveness and proliferative cell nuclear index

    Directory of Open Access Journals (Sweden)

    OSWALDO INÁCIO DE TELLA JR

    2000-12-01

    Full Text Available Analisamos 76 pacientes com adenomas hipofisários do ponto de vista clínico, radiológico e tratamento cirúrgico. Todos os casos foram estudados por imuno-histoquímica e em 49 pacientes foi pesquisado o anticorpo monoclonal PCNA. Os adenomas bi-hormonais foram os mais frequentes seguidos dos prolactinomas e os adenomas não secretantes. Os adenomas bi-hormonais não secretantes e os produtores de subunidade alfa foram proporcionalmente mais invasivos pelos critérios radiológicos. A maioria dos pacientes (59 foi operada por via transeptoesfenoidal, em seis casos a via transcraniana foi realizada e em 11 pacientes houve necessidade das duas abordagens. A ressecção foi total em 32 pacientes, a maioria em microadenomas, subtotal em 15 e parcial em 29. A complicação endócrina mais frequente foi diabetes insipidus. Houve tendência de associação positiva para os adenomas secretantes e PCNA mais elevado, assim como relação positiva quando analisamos os adenomas invasivos pela tomografia computadorizada ou ressonância magnética e o PCNA 3 e 4. A melhora visual foi observada em 85% dos macroadenomas, mesmo quando a ressecção foi parcial ou subtotal.We evaluated clinically, radiologically and surgically a series of 76 pituitary adenomas. All cases were assessed immunohistochemically and in 49 patients the PCNA monoclonal antibody was measured. The most frequent types found were the bihormonal adenomas, followed by prolactinomas and non secreting adenomas. The bihormonal adenomas, non secreting adenonas and the sub unit alfa producing adenomas were proportionally more invase as determined by radiological criteria (CTscan or MRI. In 59 patients a transphenoidal approach was used, six cases were operated on transcranially and in 11 patients we used a combination of both approach. Total resection were achieved in 32 cases, most of which were microadenomas, in 15 cases the resection was subtotal and partial in 29 cases. Diabetes insipidus

  6. Tumores hipofisarios en la tercera edad Pituitary tumors in the elderly

    Directory of Open Access Journals (Sweden)

    D Moncet

    2010-04-01

    grupo etario.World population has been growing and aging; and pituitary tumors prevalence among the elderly has also increased, summing up to 10-15% of all pituitary tumors. Thirty six elderly patients with pituitary tumors, 20 of them male, were evaluated restrospectively (average age 71 years, range 65-85. A non-functioning adenoma (NFA prevalence was reported in 64% of the cases, followed by acromegaly, prolactinoma and one each of Cushing´s disease, lymphocytic hypophysitis, craniopharyngioma, and Rathke's pouch cyst. Macroadenomas accounted for 89% of tumors and the most frequent presentation was through visual disorders symptoms followed by incidental finding and hormone hypersecretion. During biochemical evaluation, most patients presented different degrees of hypopituitarism, and patients with macroprolactinoma had PRL levels>800ng/ml. Twenty one patients (58% underwent surgery, while 9 underwent radiotherapy. During the 3.6 years follow-up, changes in adenoma size were reported in 3 patients who received no treatment (in 2 cases size increased, whereas in another it decreased. Medical treatment was indicated for those whose pathology persisted or as primary treatment if comorbilities prevented from performing a surgery. No pituitary function improvement was detected after surgery and the appearance of one or more deficiency was noticed in 62% of patients, though visual field did improve in 67%. Definitive diabetes insipidus as a complication was only detected in two patients, and a case of fistula and meningitis was observed. As a conclusion, we reported a NFA prevalence rate smaller than that reported in the world literature, though similar for the other pituitary tumors, and a higher rate of incidental presentation. No complications attributable to patients' age group were detected during surgery. For elderly patients who do not undergo surgery, clinical and imaging follow-up and/or medical treatment could be an option of choice.

  7. FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors.

    Science.gov (United States)

    Ezzat, Shereen; Wang, Ri; Pintilie, Melania; Asa, Sylvia L

    2017-01-10

    We reported that a single nucleotide polymorphism (SNP) at codon 388 of the fibroblast growth factor receptor 4 (FGFR4-Gly388Arg) can result in distinct proteins that alter pituitary cell growth and function. Here, we examined the differential properties of the available therapeutic somatostatin analogs, octreotide and pasireotide, in pituitary tumor cells expressing the different FGFR4 isoforms. Consistent with their enhanced growth properties, FGFR4-R388-expressing cells show higher mitochondrial STAT3 serine phosphorylation driving basal and maximal oxygen consumption rate (OCR) than pituitary cells expressing the more common FGFR4-G388 isoform. While both somatostatin analogs reduce the OCR in FGFR4-G388 cells, pasireotide was more effective in decreasing OCR in cells expressing the variant FGFR4-R388 isoform. Down-regulation of somatostatin receptor 5 (SSTR5) abrogated the effect of pasireotide, demonstrating its involvement in mediating this action. The effects on OCR were recapitulated by introducing a constitutively active serine STAT3 but not by a tyrosine-active mutant. Moreover, pharmacologic inhibition demonstrated the role for the phosphatase PP2A in mediating the dephosphorylation of STAT3-S727 by pasireotide. Our data indicate that FGFR4 polymorphic isoforms mediate signaling that yields mitochondrial therapeutic targets of relevance to the actions of different somatostatin analogs.

  8. JAK2V617F/STAT5 signaling pathway promotes cell proliferation through activation of Pituitary Tumor Transforming Gene 1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xu-Liang [Department of Hematology, Heping Hospital of Changzhi Medical College, Changzhi 046000 (China); Department of Hematology, Xiangya Hospital of Centre-South University, Changsha 410008 (China); Wei, Wu; Xu, Hong-Liang; Zhang, Mei-Xiang; Qin, Xiao-Qi; Shi, Wen-Zhi; Jiang, Zhi-Ping [Department of Hematology, Heping Hospital of Changzhi Medical College, Changzhi 046000 (China); Chen, Yi-Jian [Department of Hematology, The First Affiliated Hospital, GanNan Medical University, GanZhou 341000 (China); Chen, Fang-Ping, E-mail: xychenfp@2118.cn [Department of Hematology, Xiangya Hospital of Centre-South University, Changsha 410008 (China)

    2010-08-06

    Research highlights: {yields} AG490, a member of tyrosine kinase inhibitors, could inhibit the JAK2V617F/STAT5 signaling pathway in HEL cell which harbor JAK2V617F mutation. {yields} Inhibition of the JAK2V617F/STAT5 signaling pathway inhibited the growth of HEL cells. {yields} JAK2V617F mutation promotes cell proliferation through activation of PTTG1 expression. {yields} JAK2V617F/STAT5 signaling pathway regulate PTTG1 expression at transcriptional level. -- Abstract: Gain-of-function mutations of JAK2 play crucial roles in the development of myeloproliferative neoplasms; however, the underlying downstream events of this activated signaling pathway are not fully understood. Our experiment was designed and performed to address one aspect of this issue. Here we report that AG490, a potent JAK2V617F kinase inhibitor, effectively inhibits the proliferation of HEL cells. Interestingly, AG490 also decreases the expression of PTTG1, a possible target gene of the aberrant signaling pathway, in a dose- and time-dependent manner. Furthermore, the promoter activity analyses reveal that the inhibition of the PTTG1 expression is affected at the transcriptional level. Thus, our results suggest that the JAK2V617F/STAT5 signaling pathway promotes cell proliferation through the transcriptional activation of PTTG1.

  9. Analysis of internet-based patient education materials related to pituitary tumors.

    Science.gov (United States)

    Cherla, Deepa V; Sanghvi, Saurin; Agarwal, Nitin; Eloy, Jean Anderson; Couldwell, William T; Liu, James K

    2014-10-01

    The Internet has become a primary and ubiquitous information source for patient education material (PEM); however, the information provided may not be appropriate for the average patient to comprehend. Various national healthcare organizations have recommended that PEM be written at or below the sixth-grade level. The purpose of this study was to assess the readability of pituitary tumor-related PEMs available on the Internet. Fifty-one PEMs on pituitary tumors were downloaded from professional society and clinical practice websites. Analysis of readability was performed using 4 different readability indices: Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG), and Gunning Frequency Measure of Gobbledygook (Gunning FOG). Scores from the FKGL, SMOG, and Gunning FOG scales correspond to reading grade levels. Therefore, a higher number corresponds to higher difficulty and lower readability. The average grade level of the PEMs according to the readability indices were as follows: FKGL = 11.71 (11th to 12th grades), SMOG = 14.56 (college level), and Gunning FOG = 14.86 (college level). For the FRES, higher scores imply easier readability. The average FRES was 40.19 (fairly difficult-between 10th and 11th grades). These findings suggest that online pituitary tumor-related material may be too difficult for comprehension by the majority of the targeted patient population. Keeping the reading level of PEMs at or below the sixth grade may improve understanding of this disease and its management for pituitary tumor patients.

  10. Complications Following Primary and Revision Transsphenoidal Surgeries for Pituitary Tumors

    Science.gov (United States)

    Krings, James G.; Kallogjeri, Dorina; Wineland, Andre; Nepple, Kenneth G.; Piccirillo, Jay F.; Getz, Anne E.

    2014-01-01

    Objective This study aimed to determine the incidence of major complications following both primary and revision transsphenoidal pituitary surgery. Major complications included endocrinopathic, skull base, orbital, hemorrhagic and thromboembolic complications, respiratory failure, and death. Secondarily, this study aimed to examine factors associated with the occurrence of complications. Study Design Retrospective cohort analysis of California and Florida all-payer databases from 2005-2008. Methods The major complication rate following both primary and revision transsphenoidal pituitary surgery was calculated. Bivariate analyses were performed to investigate the relationship of patient characteristics with complication occurrence, and a multivariate model was constructed to determine risk factors associated with these complications. Results 5,277 primary cases and 192 revision cases met inclusion criteria. There was a non-significant absolute difference of 3.09% (95% CI −11.00 to 16.14) between the rate of complications following primary (n=443; 8.39%) and revision (n=22; 11.46%) surgeries. Multivariate analyses showed that patients with Medicare (OR=1.74; 95% CI 1.17 to 2.61), Medicaid (OR=2.13; 95% CI 1.59 to 2.86), or a malignant neoplasm (OR=3.10; 95% CI 1.62 to 5.93) were more likely to have complications. Conclusions The rate of major complications following transsphenoidal pituitary surgery is lower than earlier retrospective reports. The overall complication rate following revision surgery was not significantly different from primary surgery. Insurance status and a diagnosis of a malignant neoplasm were associated with a higher rate of complications. PMID:25263939

  11. Downregulation of miR-410 targeting the cyclin B1 gene plays a role in pituitary gonadotroph tumors

    Science.gov (United States)

    Müssnich, Paula; Raverot, Gerald; Jaffrain-Rea, Marie-Lise; Fraggetta, Filippo; Wierinckx, Anne; Trouillas, Jacqueline; Fusco, Alfredo; D'Angelo, Daniela

    2015-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs that act as posttranscriptional regulators of gene expression, and are frequently altered in human neoplasias. Here, we have analyzed the miRNA expression profile of human gonadotroph adenomas versus normal pituitary tissue using a miRNACHIP microarray. We demonstrate that miRNA-410 is downregulated in gonadotroph adenomas when compared with normal pituitary gland. We validate CCNB1 as target of miRNA-410 since its overexpression reduces CCNB1 at protein and mRNA levels, decreasing cell proliferation. In conclusion, our study suggess that the downregulation of miRNA-410 plays a role in the behavior of gonadotroph tumors. PMID:26125663

  12. Adenoid Cystic Carcinoma Metastatic to the Pituitary: A Case Report and Discussion of Potential Diagnostic Value of Magnetic Resonance Elastography in Pituitary Tumors.

    Science.gov (United States)

    D Hughes, Joshua; Retzlaff, Amber; Sims, John; O'Brien, Erin; Giannini, Caterina; Huston, John; Van Gompel, Jamie J

    2016-07-01

    Adenoid cystic carcinoma (ACC) is an exocrine gland tumor accounting for approximately 10%-15% of all epithelial salivary neoplasms and occurs most often in the parotid and submandibular glands. Metastatic pituitary tumors are rare, and there is only 1 previously reported case of parotid ACC metastatic to the pituitary. Magnetic resonance elastography (MRE) is a dynamic magnetic resonance imaging (MRI)-based technique that measures the propagation of mechanically induced shear waves through a particular tissue to determine stiffness and offers a method to evaluate tissue consistency. We present the case of a 72-year-old woman with a remote history of parotid gland ACC and subsequent lung metastases presented after a fall that resulted in facial trauma. A non-contrast head computed tomography scan revealed a sellar/suprasellar mass, and follow-up MRI revealed a well-defined, enhancing 3.8-cm lesion. MRE showed the tumor to be firm. The tumor was resected through a transsphenoidal approach and was consistent with the MRE findings. Pathology returned as metastatic ACC. We report the second case of ACC metastatic to pituitary and the first firm pituitary tumor found by MRE and discuss the potential diagnostic value of MRE in pituitary lesions.

  13. Aggressive and malignant prolactin pituitary tumors: pathological diagnosis and patient management.

    Science.gov (United States)

    Zemmoura, Ilyess; Wierinckx, Anne; Vasiljevic, Alexandre; Jan, Michel; Trouillas, Jacqueline; François, Patrick

    2013-12-01

    According to the World Health Organization classification of pituitary tumors, only tumors with systemic metastasis must be considered as carcinomas. Invasive tumors with multiple recurrences are only classified as aggressive tumors or "atypical adenomas". To illustrate the problems encountered in the pathological diagnosis of pituitary carcinoma and in patient management, we present two male patients operated on for an aggressive prolactin pituitary adenoma with and without metastasis. In case 1, 5 surgeries, 3 irradiations, increased doses of dopamine agonists, and trials of temozolomide and carboplatine-VP16 failed to control tumor progression and the appearance of metastases which lead to death 16 years after onset. In case 2, based on the initial diagnosis of an aggressive-invasive adenoma that was resistant to dopamine agonists, gamma-Knife irradiation was initially performed on the intra-cavernous remnant. Eight years after onset, the remnant remained stabilized and the plasma PRL normalized under dopamine agonist. From these 2 cases alongside other cases found in the literature, we propose that the association of certain clinical signs (male sex, dopamine-resistant hyperprolactinemia), radiological signs (invasive macro or giant tumor on MRI) and histological signs (angiogenesis, Ki-67 > 3%, p53 positive, mitoses >2 per high power field, vascular invasion, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) might suggest aggressiveness and be suspicious of malignancy before the appearance of metastasis. The early detection of an aggressive phenotype of a prolactin pituitary tumor should permit the earlier establishment of the optimum therapeutic strategy associating surgery and radiotherapy to delay or inhibit metastasis.

  14. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  15. Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.

    Science.gov (United States)

    Tourtelot, John B; Vesely, David L

    2013-08-01

    A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

  16. [Trans-septal endoscopic approach of pituitary tumors].

    Science.gov (United States)

    Muñoz del Castillo, F; Jurado Ramos, A; De la Riva Aguilar, A; López Villarejo, P

    2003-10-01

    The advances in endoscopic instruments have eased the approach to the sellar region through the nasal cavity. We carry out an analysis of the surgical results on 20 patients that underwent surgery for sellar tumours through a transeptal-transphenoidal approach in the last 2 years in our hospital. The average was 45.6 years old, and 75% were females. 30% of cases were pituitary adenomas and another 30% acromegaly, 25% Cushing's disease and 10% prolactinomas. No complications were encountered during surgery being the most common postoperative complications, diabetes insipida in two cases (10%) and CSF leak in one case. At present 2 patients are having hormonal treatment for panhypopituitarism. No patients developed a septal perforation, nasal deformity, epistaxis, meningitis, lip numbness or oronasal fistula. The rest did have good results noith no recurrence and hormonal values back to normal.

  17. The role of calcium-sensing receptor and signalling pathways in the pathophysiology in two in vitro models of malignant hypercalcemia: the rat rice H-500 Leydig testis cancer and prostate cancer (PC-3) cells. Expression and regulation of pituitary tumor transforming gene in Leydig testis cancer and astrocyte and astrocytoma cells

    DEFF Research Database (Denmark)

    Tfelt-Hansen, J.

    2008-01-01

    studies. The CaR upregulated the release of parathyroid hormone-related peptide (PTHrP), the main mediator of hypercalcemia in HHM. The growth rate of the tumor was also increased by stimulation of the CaR, as DNA synthesis and protection against apoptosis were enhanced. The oncogene, pituitary tumor...

  18. Pituitary tumor disappearance in a patient with newly diagnosed acromegaly primarily treated with octreotide LAR.

    Science.gov (United States)

    Resmini, E; Murialdo, G; Giusti, M; Boschetti, M; Minuto, F; Ferone, D

    2005-02-01

    We describe the case of an acromegalic patient primarily treated with octreotide LAR in whom the pituitary tumor disappeared after 18 months of treatment. A 68-yr-old woman, with clinical suspicion of acromegaly, was admitted to our Unit with the ultrasonographical evidence of cardiac hypertrophy, arrhythmias, right branch block and interatrial septum aneurism. She referred hands and feet enlargement since the age of 30 and facial disfigurements since the age of 50. At the age of 45 she underwent surgery for carpal tunnel syndrome and at the age of 61 an euthyroid nodular goiter was diagnosed. Hormonal evaluation showed elevated circulating GH levels (25+/-3.2 ng/ml), not suppressible after oral glucose load, and elevated IGF-I levels (646 ng/ml), whereas the remaining pituitary function was normal. Visual perimetry was normal, whereas magnetic resonance imaging (MRI) showed an intrasellar pituitary adenoma with maximal diameter of 9 mm. In order to improve cardiovascular function before surgery, the patient started octreotide LAR 20 mg every 4 weeks for 3 months. Then based on IGF-I values, the dose was adjusted to 30 mg. After 6 months a second MRI showed significant tumor reduction (>50% of baseline maximal diameter), GH and IGF-I were within the normal range and the patient continued the treatment. After one-year therapy, an improvement of cardiac alterations was recorded and the patient was referred to the neurosurgeon. However, she refused the operation. At 18-month follow-up, MRI showed the complete disappearance of direct and indirect signs of pituitary adenoma. To our knowledge, this is the first case of complete radiological remission of pituitary tumor during octreotide LAR treatment in acromegaly.

  19. Electrophoretic separation of kidney and pituitary cells on STS-8

    Science.gov (United States)

    Morrison, D. R.; Nachtwey, D. S.; Barlow, G. H.; Cleveland, C.; Lanham, J. W.; Farrington, M. A.; Hatfield, J. M.; Hymer, W. C.; Todd, P.; Wilfinger, W.; Grindeland, R.; Lewis, M. L.

    A Continuous Flow Electrophoresis System (CFES) was used on Space Shuttle flight STS-8 to separate specific secretory cells from suspensions of cultured primary human embryonic kidney cells and rat pituitary cells. The objectives were to isolate the subfractions of kidney cells that produce the largest amounts of urokinase (plasminogen activator), and to isolate the subfractions of rat pituitary cells that secrete growth hormone, prolactin, and other hormones. Kidney cells were separated into more than 32 fractions in each of two electrophoretic runs. Electrophoretic mobility distributions in flight experiments were spread more than the ground controls. Multiple assay methods confirmed that all cultured kidney cell fractions produced some urokinase, and five to six fractions produced significantly more urokinase than the other fractions. Several fractions also produced tissue plasminogen activator. The pituitary cells were separated into 48 fractions in each of the two electrophoretic runs, and the amounts of growth hormone (GH) and prolactin (PRL) released into the medium for each cell fraction were determined. Cell fractions were grouped into eight mobility classes and immunocytochemically assayed for the presence of GH, PRL, ACTH, LH, TSH, and FSH. The patterns of hormone distribution indicate that the specialized cells producing GH and PRL are isolatable due to the differences in electrophoretic mobilities.

  20. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    Science.gov (United States)

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Follow-up of patients with pituitary tumors before and after operation, medical treatment and radiotherapy

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    Gasser, R.W.; Finkenstedt, G.; Skrabal, F. (Innsbruck Univ. (Austria). Medizinische Klinik)

    1981-01-01

    From 1976 till 1981 56 patients with pituitary tumors were observed. From a total of 51 adenomas 17 prolactinomas (33.3%), 15 acromegalies (29.4%), 4 Cushing-syndromes (7.8%), 1 TSH-producing adenoma (1.9%) and 14 hormone-inactive adenomas (27.4%) were found. In addition, there were 4 craniopharyngeomas and 1 intrasellar meningeoma. For the individual types of adenomas prae- and postoperative hormonal data after transcranial resp. transsphenoidal adenomectomy are listed. Prolactinomas responded well to bromocriptine therapy in some cases, whereas acromegalies showed no remission after bromocriptine. After radiotherapy of 4 recidive-adenomas remission in one case was seen. Problems and objects of long-term-care of patients with pituitary tumors are discussed.

  2. Brain and Optic Chiasm Herniation into Sella after Pituitary Tumor Apoplexy

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    Maria M. Pineyro

    2017-08-01

    Full Text Available Brain and optic chiasm herniation has been rarely reported following dopamine agonist treatment for large prolactinomas. We report a case of brain and optical chiasm herniation, secondary to an empty sella due to apoplexy of a prolactinoma, and we focus on the specific presentation of this case. A 32-year-old female presented to a neurologist complaining of headaches. Her past medical history was significant for acute vision loss in both eyes accompanied by right third nerve palsy when she was 16 years old. She does not recall any endocrine or imaging evaluation at that time and she had spontaneous partial recovery of left eye vision within 3 months, with permanent blindness of right eye. She did not return to any follow-up until her neurologist consultation. Brain magnetic resonance imaging (MRI revealed herniation of frontal lobe and optic chiasm into the pituitary sella, as well as a pituitary hypointense lesion measuring 5 mm × 5 mm after gadolinium injection. Prolactin levels were 206 ng/ml (4.79–23.3 ng/ml. Repeated prolactin was 258 ng/ml (4.79–23.3 ng/ml. She was started on bromocriptine 2.5 mg/day. Prolactin levels and menstrual cycles normalized. A repeat brain MRI performed 5 months later showed disappearance of pituitary mass, with no changes in brain and chiasmal herniation. To our knowledge, this is the first reported case of brain associated with chiasm herniation secondary to pituitary apoplexy of a prolactinoma. In conclusion, this case highlights that frontal lobe herniation in combination with optic chiasm herniation can be a complication of pituitary tumor apoplexy. Long-term surveillance of patients with pituitary apoplexy is warranted to detect delayed complications.

  3. Testosterone Replacement and Bone Mineral Density in Male Pituitary Tumor Patients

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    Min Jeong Lee

    2014-03-01

    Full Text Available BackgroundHypopituitarism is associated with osteoporosis and osteopenia especially when hypogonadotropic hypogonadism is present. Despite hypopituitarism being an important cause of secondary osteoporosis, osteoporosis in patients receiving surgery for pituitary tumors in Korea has not been studied. In this study, we evaluated the effects of testosterone replacement therapy (TRT on bone mineral density (BMD in postoperative hypogonadal patients with pituitary tumors.MethodsTo examine the effect of TRT on BMD, we performed a retrospective observational study in 21 postoperative male patients who underwent pituitary tumor surgery between 2003 and 2012 at the Ajou University Hospital. Testosterone was replaced in postoperative hypogonadal patients by regular intramuscular injection, daily oral medication, or application of transdermal gel. BMD (g/cm2 measurements of central skeletal sites (lumbar spine, femoral neck, and total femur were obtained using dual-energy X-ray absorptiometry (GE Lunar. For lumbar spine BMD, L1 to L4 values were chosen for analysis. Femur neck and total femur were also analyzed.ResultsDuring the follow-up period (mean, 56 months; range, 12 to 99 months serum testosterone levels increased with the administration of TRT (P=0.007. There was significant improvement (4.56%±9.81% in the lumbar spine BMD compared to baseline BMD. There were no significant changes in the femur neck BMD or total femur BMD. We did not find any statistically significant relationships between changes in testosterone levels and BMD using Spearman correlation analysis.ConclusionOur results indicated that TRT used in the postoperative period for hypogonadal pituitary tumor surgery patients may have beneficial effects on the BMD of the spine.

  4. Metaphyseal giant cell tumor

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    Pereira, L.F.; Hemais, P.M.P.G.; Aymore, I.L.; Carmo, M.C.R. do; Cunha, M.E.P.R. da; Resende, C.M.C.

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed.

  5. Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells.

    Science.gov (United States)

    Vlotides, George; Chen, Yen-Hao; Eigler, Tamar; Ren, Song-Guang; Melmed, Shlomo

    2009-07-01

    To investigate paracrine regulation of pituitary cell growth, we tested fibroblast growth factor (FGF) regulation of TtT/GF folliculostellate (FS) cells. FGF-2, and FGF-4 markedly induced cell proliferation, evidenced by induction of pituitary tumor transforming gene-1 (Pttg1) mRNA expression and percentage of cells in S phase. Signaling for FGF-2-induced FS cell proliferation was explored by specific pharmacological inhibition. A potent inhibitory effect on FGF-2 action was observed by blocking of Src tyrosine kinase with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine (>or=0.1 microm), followed by protein kinase C (PKC) inhibition with GF109203X. Treatment with FGF-2 (30 ng/ml; 10 min) activated phosphorylation of signal transducer and activator of transcription-3, ERK, stress-activated protein kinase/c-Jun N-terminal kinase, Akt, and focal adhesion kinase. Src inhibition with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine suppressed FGF-2-induced Akt and focal adhesion kinase, indicating effects downstream of FGF-2-induced Src activation. FGF-2 also markedly induced its own mRNA expression, peaking at 2-4 h, and this effect was suppressed by Src tyrosine kinase inhibition. The PKC inhibitor GF109203X abolished FGF-2 autoinduction, indicating PKC as the primary pathway involved in FGF-2 autoregulation in these cells. In addition to pituitary FGF-2 paracrine activity on hormonally active cells, these results show an autofeedback mechanism for FGF-2 in non-hormone-secreting pituitary FS cells, inducing cell growth and its own gene expression, and mediated by Src/PKC signaling.

  6. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

    Science.gov (United States)

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.

  7. Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells.

    Science.gov (United States)

    Avila-Rodríguez, Dulce; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Solano-Agama, Carmen; Ortiz-Plata, Alma; Mendoza-Garrido, María E

    2016-02-18

    A three-dimensional culture method is described in which primary pituitary adenoma cells are grown in alginate beads. Alginate is a polymer derived from brown sea algae. Briefly, the tumor tissue is cut into small pieces and submitted to an enzymatic digestion with collagenase and trypsin. Next, a cell suspension is obtained. The tumor cell suspension is mixed with 1.2% sodium alginate and dropped into a CaCl2 solution, and the alginate/cell suspension is gelled on contact with the CaCl2 to form spherical beads. The cells embedded in the alginate beads are supplied with nutrients provided by the culture media enriched with 20% FBS. Three-dimensional culture in alginate beads maintains the viability of adenoma cells for long periods of time, up to four months. Moreover, the cells can be liberated from the alginate by washing the beads with sodium citrate and seeded on glass coverslips for further immunocytochemical analyses. The use of a cell culture model allows for the fixation and visualization of the actin cytoskeleton with minimal disorganization. In summary, alginate beads provide a reliable culture system for the maintenance of pituitary adenoma cells.

  8. The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis.

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    Toru Tateno

    2011-12-01

    Full Text Available Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP substituting an arginine (R for glycine (G in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL production, FGFR4-R388 cells express predominantly growth hormone (GH. Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3. In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders.

  9. The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis.

    Science.gov (United States)

    Tateno, Toru; Asa, Sylvia L; Zheng, Lei; Mayr, Thomas; Ullrich, Axel; Ezzat, Shereen

    2011-12-01

    Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders.

  10. Characterization of murine pituitary-derived cell lines Tpit/F1, Tpit/E and TtT/GF.

    Science.gov (United States)

    Yoshida, Saishu; Higuchi, Masashi; Ueharu, Hiroki; Nishimura, Naoto; Tsuda, Mitsuyoshi; Yako, Hideji; Chen, Mo; Mitsuishi, Hideo; Sano, Yoshiya; Kato, Takako; Kato, Yukio

    2014-01-01

    The pituitary is an important endocrine tissue of the vertebrate that produces and secretes many hormones. Accumulating data suggest that several types of cells compose the pituitary, and there is growing interest in elucidating the origin of these cell types and their roles in pituitary organogenesis. Therein, the histogenous cell line is an extremely valuable experimental tool for investigating the function of derived tissue. In this study, we compared gene expression profiles by microarray analysis and real-time PCR for murine pituitary tumor-derived non-hormone-producing cell lines TtT/GF, Tpit/F1 and Tpit/E. Several genes are characteristically expressed in each cell line: Abcg2, Nestin, Prrx1, Prrx2, CD34, Eng, Cspg4 (Ng2), S100β and nNos in TtT/GF; Cxcl12, Raldh1, Msx1 and Twist1 in Tpit/F1; and Cxadr, Sox9, Cdh1, EpCAM and Krt8 in Tpit/E. Ultimately, we came to the following conclusions: TtT/GF cells show the most differentiated state, and may have some properties of the pituitary vascular endothelial cell and/or pericyte. Tpit/F1 cells show the epithelial and mesenchymal phenotypes with stemness still in a transiting state. Tpit/E cells have a phenotype of epithelial cells and are the most immature cells in the progression of differentiation or in the initial endothelial-mesenchymal transition (EMT). Thus, these three cell lines must be useful model cell lines for investigating pituitary stem/progenitor cells as well as organogenesis.

  11. Pituitary tumor transforming gene binding factor: a new gene in breast cancer.

    Science.gov (United States)

    Watkins, Rachel J; Read, Martin L; Smith, Vicki E; Sharma, Neil; Reynolds, Gary M; Buckley, Laura; Doig, Craig; Campbell, Moray J; Lewy, Greg; Eggo, Margaret C; Loubiere, Laurence S; Franklyn, Jayne A; Boelaert, Kristien; McCabe, Christopher J

    2010-05-01

    Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17beta-estradiol in estrogen receptor alpha (ERalpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ERalpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ERalpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects.

  12. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly.

    Science.gov (United States)

    Colao, Annamaria; Auriemma, Renata S; Pivonello, Rosario

    2016-04-01

    In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the increased mortality to normal rates. Therapeutic strategies aim to minimize tumor mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical treatment of choice in acromegaly, as first-line or post-surgical therapy, and have proven efficacy in pituitary tumor volume reduction (TVR). Here we review the effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. TVR with somatostatin analogues may be mediated by direct anti-proliferative effects via activation of somatostatin receptors, or by indirect effects, such as angiogenesis inhibition, and is more pronounced when they are administered as first-line therapy. Various studies of first-line treatment with octreotide LAR have shown significant TVR in ≥73% of patients. First-line treatment with lanreotide Autogel has shown evidence of TVR, although more studies are needed. In a recent randomized, double-blind, 12-month trial in 358 medical-treatment-naïve acromegaly patients, significant TVR was achieved by 81% of patients administered pasireotide LAR and 77% administered octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR and improve post-operative disease control compared with surgery alone. TVR is progressive with prolonged treatment, and decreased IGF-1 levels may be its best predictor, followed by age and degree of GH decrease. However, TVR does not always correlate with degree of biochemical control. Somatostatin analogues (first- or second-line treatment) are the mainstay of medical therapy and, as first-line medical therapy, are associated with significant pituitary TVR in most patients.

  13. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

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    Oscar D. Bruno

    2015-01-01

    Full Text Available We evaluated results of temozolomide (TMZ therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson’s syndrome no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing’s disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

  14. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

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    Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

    1986-08-01

    Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release.

  15. GROWTH HORMONE-, ALPHA-SUBUNIT AND THYROTROPIN-COSECRETING PITUITARY-ADENOMA IN FAMILIAL SETTING OF PITUITARY-TUMOR

    NARCIS (Netherlands)

    LINKS, TP; MONKELBAAN, JF; DULLAART, RPF; VANHAEFTEN, TW

    1993-01-01

    A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His deceased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth fac

  16. Tumor cell metabolism

    Science.gov (United States)

    Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B´ez-Viveros, José Luis; Aguilar-Cazares, Dolores

    2011-01-01

    Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

  17. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

    Science.gov (United States)

    Hashimoto, K; Makino, S; Hirasawa, R; Takao, T; Kageyama, J; Ogasa, T; Ota, Z

    1990-06-01

    We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  18. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

    Directory of Open Access Journals (Sweden)

    Hashimoto,Kozo

    1990-06-01

    Full Text Available We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH, 1 micrograms/kg growth hormone releasing hormone (GRH, 500 micrograms thyrotropin-releasing hormone (TRH, 100 micrograms luteinizing hormone releasing hormone (LH-RH, and a relatively small dose (5 mU/kg of lysine vasopressin (LVP. In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH, prolactin (PRL and follicle-stimulating hormone (FSH responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  19. Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

    Science.gov (United States)

    Wakabayashi, I; Inokuchi, K; Hasegawa, O; Sugihara, H; Minami, S

    1992-02-01

    Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

  20. Dentinogenic ghost cell tumor

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    Singhaniya Shikha

    2009-01-01

    Full Text Available Dentinogenic ghost cell tumor (DGCT is a rare tumorous form of calcifying odontogenic cyst and only a small number of cases have been described. It is a locally invasive neoplasm that is characterized by ameloblastoma-like epithelial islands, ghost cells and dentinoid. The present report describes a case of a 21-year-old male with a tumor in the posterior region of the mandible, showing features of DGCT.

  1. Olfactory ensheathing cell tumor

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    Ippili Kaushal

    2009-01-01

    Full Text Available Olfactory ensheathing cells (OECs are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

  2. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    Science.gov (United States)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  3. Sellar collision tumor involving metastatic lung cancer and pituitary adenoma: radiologic-pathologic correlation and review of the literature.

    Science.gov (United States)

    Sogani, Julie; Yang, Wanhua; Lavi, Ehud; Zimmerman, Robert D; Gupta, Ajay

    2014-01-01

    Collision tumors of the sella turcica involving metastases to pituitary adenomas are rare. We report a case of a collision tumor involving metastatic lung cancer with an emphasis on the neuroimaging and histopathological studies. A review of the literature including the diagnostic and management implications as well as pathogenetic mechanisms is also discussed.

  4. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

    Science.gov (United States)

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-03-17

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

  5. Merkel cell tumor.

    Science.gov (United States)

    Kitazawa, M; Watanabe, H; Kobayashi, H; Ohnishi, Y; Shitara, A; Nitto, H

    1987-06-01

    A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohistochemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor.

  6. Differentiation of pituitary adenomas from other sellar and parasellar tumors by {sup 99m}Tc(V)-DMSA scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Koji [Yokohama City Univ. (Japan). Medical Center; Suzuki, Shinichi; Yamamoto, Isao [Yokohama City Univ. (Japan). School of Medicine

    2003-04-01

    Pentavalent technetium-99m dimercaptosuccinic acid [{sup 99m}Tc(V)-DMSA] scintigraphy was evaluated for the differentiation of pituitary adenomas, especially non-functioning adenomas, from other sellar and parasellar lesions. Diffuse {sup 99m}Tc(V)-DMSA accumulation within the tumor was found in seven of seven non-functioning, three of four growth hormone-secreting, and seven of eight prolactin-secreting adenomas, but only partial accumulation in only two of 16 non-pituitary adenomas and normal pituitary glands. There were no significant relationship between tumor-to-background ratios and tumor size or serum hormone level. {sup 99m}Tc(V)-DMSA scintigraphy showed overall sensitivity of 81% (17/21 cases) for detecting pituitary adenomas, in particular 100% for non-functioning adenomas. {sup 99m}Tc(V)-DMSA may be useful for detecting pituitary adenomas, especially non-functioning adenomas, and for the differentiation of non-functioning pituitary adenomas from other sellar and parasellar lesions. (author)

  7. Single-cell qPCR on dispersed primary pituitary cells -an optimized protocol

    Directory of Open Access Journals (Sweden)

    Haug Trude M

    2010-11-01

    Full Text Available Abstract Background The incidence of false positives is a potential problem in single-cell PCR experiments. This paper describes an optimized protocol for single-cell qPCR measurements in primary pituitary cell cultures following patch-clamp recordings. Two different cell harvesting methods were assessed using both the GH4 prolactin producing cell line from rat, and primary cell culture from fish pituitaries. Results Harvesting whole cells followed by cell lysis and qPCR performed satisfactory on the GH4 cell line. However, harvesting of whole cells from primary pituitary cultures regularly produced false positives, probably due to RNA leakage from cells ruptured during the dispersion of the pituitary cells. To reduce RNA contamination affecting the results, we optimized the conditions by harvesting only the cytosol through a patch pipette, subsequent to electrophysiological experiments. Two important factors proved crucial for reliable harvesting. First, silanizing the patch pipette glass prevented foreign extracellular RNA from attaching to charged residues on the glass surface. Second, substituting the commonly used perforating antibiotic amphotericin B with β-escin allowed efficient cytosol harvest without loosing the giga seal. Importantly, the two harvesting protocols revealed no difference in RNA isolation efficiency. Conclusion Depending on the cell type and preparation, validation of the harvesting technique is extremely important as contaminations may give false positives. Here we present an optimized protocol allowing secure harvesting of RNA from single cells in primary pituitary cell culture following perforated whole cell patch clamp experiments.

  8. Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors.

    Science.gov (United States)

    Haji Amousha, Mohamad Reza; Sabetkish, Nastaran; Sabet Kish, Nastaran; Heshmat, Ramin; Rajabiani, Afsaneh; Saffar, Hiva; Haghpanah, Vahid; Tavangar, Seyed Mohammad

    2015-01-01

    The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study.

  9. IN VITRO CELL CULTURE AND HORMONE RADIOIMMUNOASSAY OF HUAMAN PITUITARY ADENOMAS

    Institute of Scientific and Technical Information of China (English)

    陆汉魁; 林祥通; 等

    1994-01-01

    Tissues from 30 human pituitary adenomas are monolayer-cell-cultured in vitro.Hormone secretion of GH,PRL,TSH,LH and FSH by cells into medium is detected by radioimmunoassay .The pattern and amount of hormone(s0 in the medium are used to determine the nature of the cells and thus to establish functional classification of pituitary adenomas.The results show that cell culture technique provides and easy and suitable mode for investigating the nature of pituitary adenomas.Hormone radioimmunoassay of culture medium is precise and reliable and represents the whole adenoma tissue.Further studies can lead to clearer understandngs of the pathology of pituitary adenomas.

  10. Related pituitary cell lineages develop into interdigitated 3D cell networks.

    Science.gov (United States)

    Budry, Lionel; Lafont, Chrystel; El Yandouzi, Taoufik; Chauvet, Norbert; Conéjero, Geneviève; Drouin, Jacques; Mollard, Patrice

    2011-07-26

    The pituitary gland has long been considered to be a random patchwork of hormone-producing cells. By using pituitary-scale tridimensional imaging for two of the least abundant cell lineages, the corticotropes and gonadotropes, we have now uncovered highly organized and interdigitated cell networks that reflect homotypic and heterotypic interactions between cells. Although newly differentiated corticotrope cells appear on the ventral surface of the gland, they rapidly form homotypic strands of cells that extend from the lateral tips of the anterior pituitary along its ventral surface and into the medial gland. As the corticotrope network is established away from the microvasculature, cell morphology changes from rounded, to polygonal, and finally to cells with long cytoplasmic processes or cytonemes that connect corticotropes to the perivascular space. Gonadotropes differentiate later and are positioned in close proximity to corticotropes and capillaries. Blockade of corticotrope terminal differentiation produced by knockout of the gene encoding the transcription factor Tpit results in smaller gonadotropes within an expanded cell network, particularly in the lateral gland. Thus, pituitary-scale tridimensional imaging reveals highly structured cell networks of unique topology for each pituitary lineage. The sequential development of interdigitated cell networks during organogenesis indicate that extensive cell:cell interactions lead to a highly ordered cell positioning rather than random patchwork.

  11. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Long

    2001-01-01

    [1]LIU Xu-wen, FU Pei-yu, GAO Zhi-xian. Expression of epidermal growth factor receptors in human glioma [J]. Chin J Neurosurgery 1998; 14:71.[2]Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas [J]. Proc Natl Acad Sci USA 1992; 89:4309.[3]Webster J, Ham J, Bevan JS. Preliminary characterization of growth factors secreted by human pituitary tumors [J]. J Clin Endocrinol Metab 1991; 72:687.[4]Klibanski A. Nonsecreting pituitary tumors [J]. Endocrinol Metab Clin North Am 1987; 16:793.[5]LeRiche VK, Asa SL, Ezzat S. Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness [J]. J Clin Endocrinol Metab 1996; 81:656.

  12. MRI Findings of Causalgia of the Lower Extremity Following Transsphenoidal Resection of Pituitary Tumor

    Directory of Open Access Journals (Sweden)

    D. Ryan Ormond

    2012-01-01

    Full Text Available Background. Causalgia is continuing pain, allodynia, or hyperalgesia after nerve injury with edema, changes in skin blood flow, or abnormal sudomotor activity. Here we report a case of lower extremity causalgia following elective transsphenoidal resection of a pituitary tumor in a young man. Clinical Presentation. A 33-year-old man with acromegaly underwent elective sublabial transsphenoidal resection of his pituitary tumor. During the three-hour surgery, the lower limbs were kept in a supine, neutral position with a pillow under the knees. The right thigh was slightly internally rotated with a tape to expose fascia lata, which was harvested to repair the sella. Postoperatively, he developed causalgia in a distal sciatic and common peroneal nerve distribution. Pain was refractory to several interventions. Finally, phenoxybenzamine improved his pain significantly. Conclusions. Malpositioning in the operating room resulted in causalgia in this young man. Phenoxybenzamine improved, and ultimately resolved, his symptoms. Improvement in his pain symptoms correlated with resolution of imaging changes in the distal sciatic and peroneal nerves on the side of injury.

  13. Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor

    Science.gov (United States)

    Li, Chiao-Zhu; Li, Chiao-Ching; Hsieh, Chih-Chuan; Lin, Meng-Chi; Hueng, Dueng-Yuan; Liu, Feng-Chen; Chen, Yuan-Hao

    2017-01-01

    Abstract Introduction: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. Methods and Result: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. Conclusion: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS. PMID:28072724

  14. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    OpenAIRE

    Watson Cheryl S; Jeng Yow-Jiun

    2009-01-01

    Abstract Background Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH3/B6/F10, originally subcloned from GH3 cells based on its ability to express high l...

  15. Mobilized adult pituitary stem cells contribute to endocrine regeneration in response to physiological demand.

    Science.gov (United States)

    Rizzoti, Karine; Akiyama, Haruhiko; Lovell-Badge, Robin

    2013-10-03

    Pituitary hormone deficiencies, with Growth Hormone deficiency being most frequent (1 in 3,500-10,000 births), cause significant morbidity. Regeneration of missing endocrine cells would be a significant improvement over hormone replacement therapies, which incur side effects and do not mimic physiological secretion patterns. Recent in vitro studies have identified a population of adult pituitary progenitors that express the HMG box transcription factors SOX2 and SOX9. Here, we apply cell-lineage tracing analysis to demonstrate that SOX2- and SOX9-expressing progenitors can self-renew and give rise to endocrine cells in vivo, suggesting that they are tissue stem cells. Moreover, we show that they can become mobilized and differentiate into the appropriate endocrine cell types in response to physiological stress. Our results highlight the pituitary as a model for exploring how physiological changes influence stem cell behavior and suggest that manipulation of endogenous pituitary stem cells is a potential therapeutic strategy for pituitary deficiencies.

  16. Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

    Science.gov (United States)

    Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

    2012-01-01

    Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated

  17. Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice.

    Science.gov (United States)

    El-Naggar, Shahenda M; Malik, Mohammad T; Martin, Alvin; Moore, Joseph P; Proctor, Mary; Hamid, Tariq; Kakar, Sham S

    2007-07-01

    The pituitary tumor transforming gene (PTTG)/securin is an oncogene that is involved in cell cycle regulation and sister chromatid separation. PTTG is highly expressed in various tumors including ovarian tumors, suggesting that PTTG may play a role in ovarian tumorigenesis. Overexpression of PTTG resulted in induction of cellular transformation in vitro and tumor formation in nude mice. To ascertain PTTG function in ovarian tumorigenesis, we generated a transgenic mouse model of PTTG by cloning PTTG cDNA downstream of Mullerian inhibitory substance type II receptor gene promoter (MISIIR) in order to target the ovarian surface epithelium. By screening of transgenic animals, we identified five founders (four males and one female). Using the four male founders, we developed four transgenic lines. PTTG expression was increased in ovarian surface epithelium, ovarian granulosa cells, as well as in the pituitary gland. Transgenic females did not develop any visible ovarian tumors at 8-10 months of age; however, there was an overall increase in the corpus luteum mass in transgenic ovary, suggesting increased luteinization. These changes were associated with an increase in serum LH and testosterone levels. In addition, there was a generalized hypertrophy of the myometrium of MISIIR-PTTG transgenic uteri with cystic glandular and hyperplasia of the endometrium. Based on these results, we conclude that the overexpression of PTTG may be required to initiate precancerous conditions but is not sufficient to induce ovarian tumorigenesis and may require another partner to initiate cellular transformation.

  18. Identification of a subtype-specific ENC1 gene related to invasiveness in human pituitary null cell adenoma and oncocytomas.

    Science.gov (United States)

    Feng, Jie; Hong, Lichuan; Wu, Yonggang; Li, Chuzhong; Wan, Hong; Li, Guilin; Sun, Yilin; Yu, Shenyuan; Chittiboina, Prashant; Montgomery, Blake; Zhuang, Zhengping; Zhang, Yazhuo

    2014-09-01

    Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a treatment option, but unlike the case for functional pituitary adenomas, there are almost no drug treatments available for NFPAs. Markers of invasiveness are needed to guide therapeutic decision-making and identify potential adjuvant drugs. Owing to the highly heterogeneous nature of NFPAs, little is known regarding the subtype-specific gene expression profiles associated with invasiveness. To identify important biomarkers of invasiveness, we selected 23 null cell adenomas and 20 oncocytomas. These tumors were classified as invasive or non-invasive adenomas based on magnetic resonance imaging, pathology slides and surgical findings. Firstly, we observed that there were significant differences in expression between invasive (n = 3) and non-invasive (n = 4) adenomas by gene expression microarray. A total of 1,188 genes were differentially expressed in the invasive and non-invasive adenomas. Among these 1,188 genes, 578 were upregulated and 610 were downregulated in invasive adenomas. Secondly, the expression of ENC1, which displayed the significant alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43 tumor samples and three normal pituitary glands. Low levels of ENC1 were found in tumor samples, while high levels were detected in normal pituitary glands. Interestingly, the ENC1 expression level was low in invasive null cell adenomas compared with non-invasive adenomas, but this relationship was not observed in invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of ENC1 was different between invasive and non-invasive null cell adenomas. In addition, bioinformatics studies, including gene ontology and protein interaction analyses, were also performed to better understand the critical role of ENC1 in the development and progression of null cell adenomas and oncocytomas. Consequently, ENC1 may be an important biomarker for null cell

  19. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  20. The endonasal microscopic approach for pituitary adenomas and other parasellar tumors: a 10-year experience.

    Science.gov (United States)

    Fatemi, Nasrin; Dusick, Joshua R; de Paiva Neto, Manoel A; Kelly, Daniel F

    2008-10-01

    THE DIRECT ENDONASAL transsphenoidal approach to the sella with the operating microscope was initially described more than 20 years ago. Herein, we describe the technique, its evolution, and lessons learned over a 10-year period for treating pituitary adenomas and other parasellar pathology. From July 1998 to January 2008, 812 patients underwent a total of 881 operations for a pituitary adenoma (n = 605), Rathke's cleft cyst (n = 59), craniopharyngioma (n = 26), parasellar meningioma (n = 23), chordoma (n = 18), or other pathological condition (n = 81). Of these, 118 operations (13%) included an extended approach to the suprasellar, infrasellar/clival, or cavernous sinus regions. Endoscopic assistance was used in 163 cases (19%) overall, including 36% of the last 200 cases in the series and 18 (72%) of the last 25 extended endonasal cases. Surgical complications included 19 postoperative cerebrospinal fluid leaks (2%), 6 postoperative hematomas (0.7%), 4 carotid artery injuries (0.4%), 4 new permanent neurological deficits (0.4%), 3 cases of bacterial meningitis (0.3%), and 2 deaths (0.2%). The overall complication rate was higher in the first 500 cases in the series and in extended approach cases. Major technical modifications over the 10-year period included increased use of shorter (60-70 mm) endonasal speculums for greater instrument maneuverability and visualization, the micro-Doppler probe for cavernous carotid artery localization, endoscopy for more panoramic visualization, and a graded cerebrospinal fluid leak repair protocol. These changes appear to have collectively and incrementally made the approach safer and more effective. In summary, the endonasal approach provides a minimally invasive route for removal of pituitary adenomas and other parasellar tumors.

  1. Mouse Leydig Tumor Cells

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    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  2. Thyrotropin-secreting pituitary tumor presenting with congestive heart failure and good response to dopaminergic agonist cabergoline.

    Science.gov (United States)

    Kao, Yu-Hsi; Chang, Tien-Jyun; Huang, Tien-Shang

    2013-11-01

    Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH)-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

  3. Thyrotropin-secreting pituitary tumor presenting with congestive heart failure and good response to dopaminergic agonist cabergoline

    Directory of Open Access Journals (Sweden)

    Yu-Hsi Kao

    2013-11-01

    Full Text Available Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

  4. Nonislet Cell Tumor Hypoglycemia

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    Johnson Thomas

    2013-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare cause of hypoglycemia. It is characterized by increased glucose utilization by tissues mediated by a tumor resulting in hypoglycemia. NICTH is usually seen in large mesenchymal tumors including tumors involving the GI tract. Here we will discuss a case, its pathophysiology, and recent advances in the management of NICTH. Our patient was diagnosed with poorly differentiated squamous cell carcinoma of esophagus. He continued to be hypoglycemic even after starting continuous tube feeds and D5W. General workup for hypoglycemia was negative and insulin-like growth factor II (IGF II was in the normal range. Hypoglycemia secondary to “big” IGF II was considered, and patient was started on steroids. His hypoglycemia resolved within a day of treatment with steroids. Initially patient had hypoglycemia unawareness, which he regained after maintaining euglycemia for 48 hours.

  5. Establishment and culture optimization of a new type of pituitary immortalized cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  6. Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA.

    Science.gov (United States)

    Ma, Qin-Yun; Zhang, Xiao-Na; Jiang, He; Wang, Zhi-Quan; Zhang, Hui-Jie; Xue, Li-Qiong; Chen, Ming-Dao; Song, Huai-Dong

    2011-07-20

    Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA. Copyright © 2011. Published by Elsevier Ireland Ltd.

  7. Therapy for non-functional pituitary adenoma. Residual tumor and radiotherapy

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    Takahashi, Toshio; Ito, Satoshi; Shimamura, Norihito; Sekiya, Tetsuharu; Tanaka, Masahiko; Suzuki, Shigeharu [Hirosaki Univ., Aomori (Japan). School of Medicine

    1997-01-01

    Effects and complication of radiotherapy after surgery of non-functional pituitary adenoma were evaluated with consideration on findings in recent literatures. On 44 cases of 64 patients (36 males and 28 females), the mean age of 48.9y, with macroadenoma, a comparison was made on their recurrence and complication between irradiated and non-irradiated groups after surgery. The follow-up period was >1 year (5y4m in a mean). The total radiation dose was in the range of 40-60 (average 47.3) Gy. Recurrence was seen in 1/31 cases in irradiated group, and 5/13 in non-irradiated group. Reduction of visual acuity and hypopituitarism were observed in 1 and 2 cases, respectively, in irradiated group. Radiotherapy for residual tumor was confirmed useful for preventing recurrence. (K.H.)

  8. Mice lacking pituitary tumor transforming gene show elevated exposure of DGalNAc carbohydrate determinants

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    Lutsyk A. D.

    2012-04-01

    Full Text Available Aim. To investigate the influence of pituitary tumor transforming gene (pttg-1 knockout on glycome of parenchimal organs by means of lectin histochemistry. Methods. DGalNAc, DGlcNAc, NeuNAc carbohydrate determinants were labelled with soybean agglutinin (SBA and wheat germ agglutinin (WGA, conjugated to peroxidase, with subsequent visualization of the lectin-binding sites with diaminobenzidine. The testes and kidneys of murine strain BL6/C57 with the pttg-1 gene knockout (PTTG-KO were compared to the wild type (PTTG-WT animals, both groups 1 month of age. Results. Knockout of the pttg-1 gene was accompanied by enhanced exposure of the DGalNAc sugar residues within the Golgi complex of secondary spermatocytes, in a brush border of renal tubules and on the lumenal surface of collecting ducts. Conclusions. This study suggests that knockout of the pttg-1 gene may lead to the changes in carbohydrate processing in mammalian organism.

  9. Electrophoretic separation of cells and particles from rat pituitary and rat spleen

    Science.gov (United States)

    Hymer, Wesley C.

    1993-01-01

    There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

  10. 谷胱甘肽对多巴胺诱导的GH4细胞凋亡的保护作用%Glutathione protects GH4 pituitary lactotrope tumor cells from apoptosis induced by dopamine

    Institute of Scientific and Technical Information of China (English)

    王晗; 李书鹏; 姜玉华; 刘芳

    2011-01-01

    Objective To explore mechanisms of dopamine(DA) inducing GH4 cell apoptosis and glutathione(GSH) protecting GH4 cells from apoptosis induced by DA. Methods ① GH4 pituitary cells were treated with DA at 0, 100, 300 and 500μmol/L for 24 h, then treated with DA at 500 μmol/L for 0,1,3,5,12 and 24 h to select the appropriate concentration and time. ② Then GH4 cells were treated with raclopride( a D2 receptor antagonist, Rac) and GSH to explore the effects of Rac and GSH on apoptosis. ③Apoptotic cells were counted by an inverted phase contrast microscope. Morphological appearance was observed by PI labeling, and expressions of Bcl-2 and PARP-1 were detected by Western blot. Results DA induced concentration-and time-dependent GH4 cell apoptosis. A selective D2 receptor antagonist could not block the cytotoxic effect. PI revealed that exposure to GSH (1 mmol/L) for lh prior to the DA treatment attenuated DA-induced apoptosis. Western blot showed up-regulation of Bcl-2 and down-regulation of PARP-1. Conclusion DA exerts cytotoxic effects on GH4 cells mainly through auto-oxidation in the intracellular space. A selective D2 receptor antagonist cannot block DA-induced apoptosis, while GSH can block it, which may be relevant to regulation of Bcl-2 and PARP-1.%目的 探讨多巴胺(DA)诱导垂体瘤GH4细胞凋亡及谷胱甘肽(GSH)对DA诱导细胞凋亡的保护作用机制.方法 本实验通过3部分探讨DA的凋亡作用及GSH的保护作用:①实验分空白对照组及DA用药组,体外观察不同浓度、时间DA对GH4细胞生长的影响;②实验分空白对照组、DA组、DA联合DA D2受体拮抗剂组,观察D2受体在细胞凋亡中的作用;③实验设空白对照组、DA组、GSH用药组,PI染色分别观察3组细胞的凋亡情况,Western blot检测Bcl-2及PARP-1的表达.结果 DA诱导的GH4细胞凋亡呈浓度-时间依赖性,选择性D2受体拮抗剂不能阻断细胞凋亡,经GSH处理GH4细胞后,PI染色显示凋

  11. Pituitary Tumor-Transforming Gene 1 Is Expressed in Primary Ductal Breast Carcinoma, Lymph Node Infiltration, and Distant Metastases

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    Fabio Grizzi

    2013-01-01

    Full Text Available Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1 expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.

  12. Ghost Cell Tumors.

    Science.gov (United States)

    Sheikh, Jason; Cohen, Molly D; Ramer, Naomi; Payami, Ali

    2017-04-01

    Ghost cell tumors are a family of lesions that range in presentation from cyst to solid neoplasm and in behavior from benign to locally aggressive or metastatic. All are characterized by the presence of ameloblastic epithelium, ghost cells, and calcifications. This report presents the cases of a 14-year-old girl with a calcifying cystic odontogenic tumor (CCOT) and a 65-year-old woman with a peripheral dentinogenic ghost cell tumor (DGCT) with dysplastic changes, a rare locally invasive tumor of odontogenic epithelium. The first patient presented with a 1-year history of slowly progressing pain and swelling at the left body of the mandible. Initial panoramic radiograph displayed a mixed radiolucent and radiopaque lesion. An incisional biopsy yielded a diagnosis of CCOT. Decompression of the mass was completed; after 3 months, it was enucleated and immediately grafted with bone harvested from the anterior iliac crest. The second patient presented with a 3-month history of slowly progressing pain and swelling at the left body of the mandible. Initial panoramic radiograph depicted a mixed radiolucent and radiopaque lesion with saucerization of the buccal mandibular cortex. An incisional biopsy examination suggested a diagnosis of DGCT because of the presence of ghost cells, dentinoid, and islands of ameloblastic epithelium. Excision of the mass with peripheral ostectomy was completed. At 6 and 12 months of follow-up, no evidence of recurrence was noted.

  13. Contemporary issues in the evaluation and management of pituitary adenomas.

    Science.gov (United States)

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current

  14. Association of pituitary tumor transforming gene expression with early oral tumorigenesis and malignant progression of precancerous lesions.

    Science.gov (United States)

    Liao, Li-Jen; Hsu, Yi-Hsin; Yu, Chuan-Hang; Chiang, Chun-Pin; Jhan, Jing-Ru; Chang, Lien-Cheng; Lin, Jing-Jer; Lou, Pei-Jen

    2011-05-01

    Pituitary tumor transforming gene (PTTG1) is overexpressed in many types of human cancers and is involved in late-stage tumor progression. The role of PTTG1 in initiating tumorigenesis is unclear. PTTG1 expression was assessed in precancerous lesions and squamous cell carcinomas of the oral cavity (OSCC). The association between the protein expression and clinicopathologic parameters was analyzed. The expression level of PTTG1 upon carcinogen treatment was also investigated. PTTG1 was overexpressed in both precancerous lesions and OSCC. The expression of PTTG1 was associated with carcinogen exposure in vivo and in vitro. PTTG1 overexpression was an independent factor for oral cancer development in precancerous lesions. This study provides the first evidence that PTTG1 is involved in the early stages of oral tumorigenesis. Carcinogen exposure may cause the initial induction of PTTG1 expression in oral precancerous lesions. PTTG1 overexpression is a potential prognosticator for malignant progression of oral precancerous lesions. Copyright © 2010 Wiley Periodicals, Inc.

  15. Human rhabdomyosarcoma cells express functional pituitary and gonadal sex hormone receptors: Therapeutic implications

    Science.gov (United States)

    PONIEWIERSKA-BARAN, AGATA; SCHNEIDER, GABRIELA; SUN, WENYUE; ABDELBASET-ISMAIL, AHMED; BARR, FREDERIC G.; RATAJCZAK, MARIUSZ Z.

    2016-01-01

    Evidence has accumulated that sex hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of sex hormone receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal sex hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that sex hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS. PMID:26983595

  16. Benign notochordal cell tumors.

    Science.gov (United States)

    Martínez Gamarra, C; Bernabéu Taboada, D; Pozo Kreilinger, J J; Tapia Viñé, M

    2017-08-01

    Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly.

    Science.gov (United States)

    Yamada, Shozo; Fukuhara, Noriaki; Oyama, Kenichi; Takeshita, Akira; Takeuchi, Yasuharu

    2010-10-01

    Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone-secreting pituitary adenoma. To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

  18. Extraovarian granulosa cell tumor

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    Paul Prabir

    2009-04-01

    Full Text Available Extraovarian granulosa cell tumor (GCT is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15cm x 16cm and another mesenteric mass of 8cm x 5cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

  19. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour

    Science.gov (United States)

    De Marco, Rodrigo J.; Thiemann, Theresa; Groneberg, Antonia H.; Herget, Ulrich; Ryu, Soojin

    2016-01-01

    The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. PMID:27646867

  20. Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells.

    Science.gov (United States)

    Phelps, C J; Wiggins, J P; Wangsness, P J

    1988-10-01

    A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.

  1. Inhibitory Effects of Anti-VEGF Antibody on the Growth and Angiogenesis of Estrogen-induced Pituitary Prolactinoma in Fischer 344 Rats: Animal Model of VEGF-targeted Therapy for Human Endocrine Tumors

    Science.gov (United States)

    Miyajima, Katsuhiro; Takekoshi, Susumu; Itoh, Johbu; Kakimoto, Kochi; Miyakoshi, Takashi; Osamura, Robert Yoshiyuki

    2010-01-01

    Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic “blood lakes” in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas. PMID:20514290

  2. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    A León-Suárez

    2016-12-01

    Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

  3. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  4. Effect of a long-acting somatostatin analogue (SMS 201-995 on a growth hormone and thyroid stimulating hormone-producing pituitary tumor.

    Directory of Open Access Journals (Sweden)

    Hirasawa,Ryoto

    1991-04-01

    Full Text Available A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH levels and very high serum growth hormone (GH levels. Transsphenoidal removal of the tumor, post-operative irradiation, frontal craniotomy for removal of residual tumor and large-dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH-, TSH- and follicle-stimulating hormone (FSH-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor.

  5. Pituitary prolactin adenoma with Toxoplasma gondii infection

    Institute of Scientific and Technical Information of China (English)

    张晓晖; 李青; 程虹; 阎庆国; 黄高昇

    2003-01-01

    Objective: To report two recent cases of pituitary adenoma associated with Toxoplasma gondii (T.Gondii) infection.Methods: Histological changes were observed in H & E and PAS staining sections microscopically.Immunohistochemistry was performed to classify the pituitary tumors and to confirm the diagnosis of T.gondii.Results: The cases were 43- and 19-year-old females, in which the latter one was a recurring case, and radiology examination showed that tumors existed in sellar region.Microscopically, the tumors consisted of small homogenous polygonal or round cells with abundant eosinophilic granular cytoplasm.Immunohistochemistry revealed they were prolactin-producing adenomas.Interestingly, we found toxoplasma infection in the tumor tissues, being confirmed by T.gondii sepicific antibody immunohistochemistry.Conclusion: The association of pituitary adenoma with toxoplasma raises the possibility that T.gondii may be involved in the development of certain cases of pituitary adenoma.

  6. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...

  7. Sertoli-Leydig cell tumor

    Science.gov (United States)

    Sertoli-stromal cell tumor; Arrhenoblastoma; Androblastoma; Ovarian cancer - Sertoli-Leydig cell tumor ... The exact cause of this tumor is not known. Changes (mutations) in genes may play a role. SLCT occur most often in young women 20 to 30 ...

  8. Molecular Morphology of Pituitary Cells, from Conventional Immunohistochemistry to Fluorescein Imaging

    Directory of Open Access Journals (Sweden)

    R. Yoshiyuki Osamura

    2011-04-01

    Full Text Available In situ hybridization (ISH at the electron microscopic (EM level is essential for elucidating the intracellular distribution and role of mRNA in protein synthesis. EM-ISH is considered to be an important tool for clarifying the intracellular localization of mRNA and the exact site of pituitary hormone synthesis on the rough endoplasmic reticulum. A combined ISH and immunohistochemistry (IHC under EM (EM-ISH&IHC approach has sufficient ultrastructural resolution, and provides two-dimensional images of the subcellular localization of pituitary hormone and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals (quantum dots, Qdots and confocal laser scanning microscopy (CLSM enable us to obtain three-dimensional images of the subcellular localization of pituitary hormone and its mRNA. Both EM-ISH&IHC and ISH & IHC using Qdots and CLSM are useful for understanding the relationships between protein and mRNA simultaneously in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as SNAP-25 and syntaxin has revealed that both rab3B and SNARE system proteins play important roles and work together as the exocytotic machinery in anterior pituitary cells. Another important issue is the intracellular transport and secretion of pituitary hormone. We have developed an experimental pituitary cell line, GH3 cell, which has growth hormone (GH linked to enhanced yellow fluorescein protein (EYFP. This stable GH3 cell secretes GH linked to EYFP upon stimulation by Ca2+ influx or Ca2+ release from storage. This GH3 cell line is useful for the real-time visualization of the intracellular transport and secretion of GH. These three methods from conventional immunohistochemistry and fluorescein imaging allow us to consecutively visualize the process of transcription, translation, transport and secretion of anterior pituitary hormone.

  9. Substance P enhances the proliferation of rat anterior pituitary cells in vitro

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    The undecapeptide substanceP(SP) was shown to be intimately involved in both the structural and functional aspects of the anterior pituitary.Yet,in addition to its influences on hormonal secretion,SP may well possess more actions in this master gland.The present study was ftherefore aimed to investigate the effect of SP on the proliferation of rat anterior pituitary cells in primary culture,It was found that SP could dose-dependently increase the incorporation of tritiated thymidine(3H-TdR) into cultured anterior pituitary cells.Other mammalian tachykinins such as neurokinin A and neurokinin B had similar effect but to varying degrees.The equipotent analogue of SP,Norleucine11-SP(Nle11-SP),also acted likewise.with its action antagonizable by spantide,a SP receptor blocker.To further characterize the nature of cells responsive to the challenge of SP,immunocytochemical staining against S-100 protein and some adenohypophyseal hormones was performed alone or plus autoradiography.The results showed that the percentage of S-100 proteinimmunorective cells was apparently elevated by the addtion of Nle11-Sp for 48h,which indicates a preferential proliferation of folliculo-stellate cells under the regime .This was confirmed by increases in immunocytochemical or autoradiographical labelling indices of anterior pituitary Substance P and anterior pituitary cell proliferation.Cells treated similarly.Taken together,These results reveal that the trophic action of SP observed previously in other tissues is also present at least in cultured rat anterior pituitary cells.with responding cells being predominantly folliculo-stellate cells as typified by S-100 proteinimmunoreactivity.Therefore,an intra-pituitary trophicaction of SP in vivo could be anticipated.

  10. Down-regulation of Leucine-rich Repeats and Immunoglobulin-like Domain Proteins (LRIG1-3) in HP75 Pituitary Adenoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    GUO Dongsheng; HAN Lin; SHU Kai; CHEN Jian; LEI Ting

    2007-01-01

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIG1 was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 (14-fold increase in HP75) and EGFR/LRIG3 (11-fold increase in HP75). Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.

  11. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

    Science.gov (United States)

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

  12. CROSS-SECTIONAL STUDY OF VISUAL FIELD DEFECTS IN PITUITARY GLAND TUMORS

    Directory of Open Access Journals (Sweden)

    Ananth Bhandary

    2014-08-01

    Full Text Available AIM: To study the proportion of patients with visual field defects in pituitary adenomas And to study the pattern of visual field defects in pituitary adenomas. MATERIALS AND METHODS: 24 patients diagnosed with a pituitary adenoma underwent complete ophthalmic and Humphrey’s Perimetry 30 – 2 visual field test at Department of ophthalmology, M. S Ramaiah Hospital between November 2011 to May 2013. RESULTS: Among the 24 cases in the study, 3 cases were of pituitary micro adenoma constituting 12.5% and the remaining cases (21 cases were pituitary macro adenoma, constituting 87.5%. Visual acuity of 6/6 – 6/12 were observed in 28 (58.3% out of total 48 eyes. Visual field defects were observed in 19 cases (79%. Bilateral temporal hemianopia was observed in the majority (41% of cases with field defects. One eye blind and contra lateral temporal hemianopia was observed in 20.8%. One eye temporal hemianopia and other eye involvement of 3 quadrants seen in 2 patients (8.4%. 5 patients had no visual field defects. CONCLUSION: Although ophthalmologists have a minor role in primary diagnosis of pituitary adenoma, routine ophthalmologic examination is very important. To detect early visual field defects, automated perimetry should be done as a part routine examination in patients with suspected pituitary adenoma

  13. Dengue hemorrhagic fever: A rare cause of pituitary tumor hemorrhage and reversible vision loss

    Directory of Open Access Journals (Sweden)

    Vimal Kumar

    2011-01-01

    Full Text Available Dengue hemorrhagic fever leading to hemorrhage in pituitary adenoma is not reported till date: We herein report the first case of bilateral visual loss secondary to pituitary adenoma hemorrhage associated with dengue hemorrhagic fever. Urgent transnasal trans sphenoidal decompression of the macroadenoma prevented permanent visual loss in this patient. Pituitary apoplexy should be considered as differential diagnosis of visual deterioration apart from retinal hemorrhage, maculopathy, and optic neuropathy in cases of dengue hemorrhagic fever. Early decompression of optic nerves helped in the restoration of vision.

  14. EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element.

    Science.gov (United States)

    Manfroid, Isabelle; Van de Weerdt, Cécile; Baudhuin, Ariane; Martial, Joseph A; Muller, Marc

    2005-01-14

    Normal and neoplastic human mammary gland cells are targets for the proliferative action of prolactin. These cells also synthesize prolactin, thereby inducing an autocrine/paracrine proliferative loop. We present the first extensive analysis of the transcriptional regulation of the human prolactin gene (hPRL) in human mammary tumor cells, SK-BR-3. We show that the pituitary promoter is functional in these cells in the absence of the pituitary-specific factor Pit-1. Expression of exogenous Pit-1 or epidermal growth factor (EGF) treatment stimulates the transfected hPRL pituitary promoter and the endogenous hPRL expression. EGF stimulation is mediated by increased synthesis of c-fos and c-jun, resulting in AP-1 binding to the proximal hPRL pituitary promoter. This regulation involves the EGF receptor, possibly ErbB2 that is highly expressed in SK-BR-3 cells, and a PI3K/JNK pathway. The stimulation of hPRL gene transcription by EGF in mammary cells may include hPRL in a complex regulatory network controlling growth of human mammary cells.

  15. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    Science.gov (United States)

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  16. Specific in vitro uptake of serotonin by cells in the anterior pituitary of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Johns, M.A.; Azmitia, E.C.; Krieger, D.T.

    1982-03-01

    In vivo studies have suggested that serotonin (5HT) influences anterior pituitary function at the hypothalamic level. The present in vitro study investigated the possibility that 5HT may act directly on the anterior pituitary. The high affinity uptake of (3H)5HT into adult rat anterior pituitary tissue was examined in two types of experiments. 1) To test the specificity and saturability of uptake of 5HT in the anterior pituitary, pituitary tissue was incubated (37 C) with (3H)5HT (10(-8)-10(-6) M) in the presence and absence of excess (10(-5) M) unlabeled 5HT, norepinephrine, fluoxetine (FLUOX), metergoline, or cyproheptadine. A Hofstee analysis of the specific uptake of (3H)5HT gave an apparent Km value of 4.23 x 10(-7) M and a Vmax of 1576 pmol/g/10 min (3H)5HT. The total uptake of (3H)5HT was not altered by norepinephrine or metergoline, but was significantly reduced (P less than 0.01-0.001) by FLUOX and cyproheptadine. Uptake was shown to be temperature and sodium dependent and not directly dependent on energy derived from glycolysis or aerobic metabolism. 2) To study the site of uptake of 5 HT in the anterior pituitary, in concomitant radioautographic experiments, tissue was incubated with (3H)5HT with and without excess 5HT or FLUOX. Three patterns of silver grain distribution were observed: 1) nonrandom concentrations over select anterior pituitary cells near blood vessels, 2) heavy aggregates of silver grains usually associated with blood vessels, and 3) a seemingly random dispersal of grains over pituitary tissue. Tissue incubated with (3H)5HT alone contained 10% heavily labeled cells, 32% moderately labeled cells, and 58% weakly labeled cells. In contrast, no heavily labeled cells were seen when tissue was incubated with either excess 5HT or FLUOX in addition to (3H)5HT. Our findings of saturable and specific high affinity uptake of (3H)5HT into a subgroup of anterior pituitary cells suggest a direct pituitary action of 5HT.

  17. Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

    Science.gov (United States)

    Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2017-08-01

    The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

  18. Coordinate control of corticotropin, β-lipotropin, and β-endorphin release in mouse pituitary cell cultures

    Science.gov (United States)

    Allen, Richard G.; Herbert, Edward; Hinman, Michael; Shibuya, Haruo; Pert, Candace B.

    1978-01-01

    Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D16v line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 μM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10-6 M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (β-lipotropic hormone-size material) and 3500 (β-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts. PMID:217008

  19. Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors.

    Science.gov (United States)

    Hayashi, Yasuhiko; Kita, Daisuke; Watanabe, Takuya; Fukui, Issei; Sasagawa, Yasuo; Oishi, Masahiro; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi

    2016-12-01

    Diabetes insipidus (DI) remains a complication of transsphenoidal surgery (TSS) for sellar and parasellar tumors. Antidiuretic hormone (ADH) appears as hyper intensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport. This retrospective study included 172 patients undergoing TSS for sellar tumors at our institute from 2006 to 2014. Sequential T1-weighted MR images without enhancement were evaluated for HI in the pituitary stalk and the posterior lobe to assess the localization of ADH before and at intervals after TSS. DI was assessed pre- and postoperatively. HI in the pituitary stalk showed the following morphology: (1) ovoid in the distal end of the pituitary stalk (group A), (2) linear in the distal part of the pituitary stalk (group B), (3) linear in the whole pituitary stalk (group C). Preoperative DI occurred in 6 patients (3.5 %) with no HI observed in the posterior lobe. Postoperative DI was transient in 82 patients (47.7 %), and permanent in 11 (6.4 %). One week after surgery, HI was absent in the posterior lobe in 74 patients (43.0 %), and present in the pituitary stalk in 99 patients (57.6 %); both were significantly correlated with postoperative DI (p < 0.001). The absence of HI in the posterior lobe (A, 48.9 %; B, 68.3 %; C, 92.3 %), persistence of DI (A, 3.7 days; B, 45.9 days; C, 20.5 months), and duration until HI recovery in the posterior lobe (A, 3.6 months; B, 6.8 months; C, 22.9 months) were greatest in group C, followed by group B, and then group A. Fourteen group A patients did not have postoperative DI despite having HI in the pituitary stalk and the posterior lobe. Four group C patients developed permanent DI with persistence HI in the pituitary stalk. HI in the pituitary stalk and its

  20. Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas.

    Science.gov (United States)

    Matyja, Ewa; Maksymowicz, Maria; Grajkowska, Wiesława; Zieliński, Grzegorz; Kunicki, Jacek; Bonicki, Wiesław; Witek, Przemysław; Naganska, Ewa

    2015-01-01

    Ganglion cell tumours in the sellar region are uncommon. They are usually associated with pituitary adenomas, while isolated ganglion cell neoplasms are extremely rare. We report the clinicopathological studies of five cases diagnosed as ganglion cell tumours located in the intrasellar region: four mixed/collision tumours composed of gangliocytoma and pituitary adenoma, and one isolated ganglioglioma unrelated to adenoma. Clinically, two patients presented with acromegaly, while three others were initially diagnosed as non-functioning adenomas. In four cases, the histopathological examination of surgical specimens revealed intermixed lesions composed of pituitary adenoma and ganglion cell elements. The adenomas appeared to secrete growth hormone. Electron microscopy enabled identification of the sparsely granulated somatotroph cells. Neoplastic neuronal lesions were composed of mature ganglion cells, including binucleate or multinucleate cells. In all cases, boundaries between adenomatous and gangliocytic components were not clearly demarcated, and numerous gangliocytic cells were closely intermingled with adenomatous tissue. One case lacked endocrine symptoms, and no pituitary adenoma was identified in the surgically excised material; it was finally diagnosed as low-grade ganglioglioma. The etiopathogenesis of ganglion cell neoplasms in the sellar region is not clearly defined. Our study revealed that if ganglion cell neoplasms were combined with adenoma, both neoplastic components were closely related to each other, and numerous neuronal elements were strictly intermingled with adenoma cells. Such a tissue pattern indicates that these neoplastic changes, including their common respective etiopathogeneses, are closely related. The identification of both components in sellar regions may have some nosological implications.

  1. A case of pediatric virilizing adrenocortical tumor resulting in hypothalamic-pituitary activation and central precocious puberty following surgical removal.

    Science.gov (United States)

    Miyoshi, Yoko; Oue, Takaharu; Oowari, Mitsugu; Soh, Hideki; Tachibana, Makiko; Kimura, Sadami; Kiyohara, Yuki; Yamada, Hiroyuki; Bessyo, Kazuhiko; Mushiake, Sotaro; Homma, Keiko; Hasegawa, Tomonobu; Sasano, Hironobu; Ozono, Keiichi

    2009-01-01

    We present a 6-year-old boy with a virilizing adrenocortical tumor who initially presented with peripheral precocious puberty. Development of facial acne, pubic hair and a growth spurt were noted at the age of five. A low-pitched voice as well as maturation of external genitalia was noted at the age of six. Both serum and urinary levels of adrenal androgens were elevated. Abdominal computed tomography revealed a large right suprarenal mass and he underwent surgical resection without any complications. The histological diagnosis was adrenocortical carcinoma according to the criteria of Weiss. Following surgical removal of the androgen-producing tumor, the patient subsequently developed hypothalamic-pituitary activation and demonstrated central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist in order to delay further pubertal progression. Clinical follow-up of potential secondary effects of excess hormone secretion after removal is important in some pediatric patients with virilizing adrenocortical tumor.

  2. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma

    OpenAIRE

    Cheng-Chi Lee; Chung-Ming Chen; Shih-Tseng Lee; Kuo-Chen Wei; Ping-Ching Pai; Cheng-Hong Toh; Chi-Cheng Chuang

    2015-01-01

    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective...

  3. Ovarian Germ Cell Tumors Treatment

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  4. Tumorigenic potential of pituitary tumor transforming gene (PTTG in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/− transgenic mice

    Directory of Open Access Journals (Sweden)

    Fong Miranda Y

    2012-11-01

    Full Text Available Abstract Background Pituitary tumor-transforming gene (PTTG is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Methods Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. Results PTTG transgenic offspring (TgPTTG were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells

  5. Successful Pregnancy in a Female with a Large Prolactinoma after Pituitary Tumor Apoplexy

    Directory of Open Access Journals (Sweden)

    Butheinah A. Al-Sharafi

    2013-01-01

    Full Text Available Pituitary apoplexy is a rare condition which may cause death of the patient in severe cases and many times leads to hypopituitarism. We report a case of apoplexy in a large prolactinoma resulting in empty sella syndrome followed by a successful pregnancy. Our patient is a 32-year-old female with a history of a macroprolactinoma for approximately 17 years who presented to our hospital with a history of severe headache, decreased level of consciousness, fever, nausea, vomiting, and diplopia of 12 hours duration. Magnetic resonance imaging done on admission showed an increase in the size of the pituitary adenoma with a subtle hemorrhage. The patient was admitted to the intensive care unit and treated conservatively. The condition of the patient improved within a few days. A few months later, she started having regular menstrual periods. A magnetic resonance imaging of the pituitary 1.5 years later was reported as empty sella syndrome, and approximately one year later she became pregnant. With the pituitary adenoma being resolved after developing pituitary apoplexy and continuing on cabergoline, the patient had a successful pregnancy with no recurrence of the adenoma after delivery and breastfeeding.

  6. Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway.

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    Seung Mook Lim

    Full Text Available Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1 was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence-activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1. Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP-2 and MMP-9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05. Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4, ITGA5, and integrin beta 1 (ITGB1; otherwise, RhoA expression was significantly decreased (p < 0.05. Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development.

  7. Uptake of triiodothyroacetic acid and its effect on thyrotropin secretion in cultured anterior pituitary cells

    NARCIS (Netherlands)

    M.E. Everts (Maria); T.J. Visser (Theo); E.P.C.M. Moerings (Ellis); R. Docter (Roel); H. van Toor (Hans); A.M. Tempelaars; E.P. Krenning (Eric); G. Hennemann; M. de Jong (Marion)

    1994-01-01

    textabstractThe uptake of [125I]triiodothyroacetic acid ([125I]Triac) in anterior pituitary cells was investigated and compared with that of [125I]T3. Furthermore, the effects of Triac, T3, and T4 on TSH release were compared. Cells isolated from adult male Wistar rats

  8. Gene expression profiling of pituitary melanotrope cells during their physiological activation.

    NARCIS (Netherlands)

    Kuribara, M.; Bakel, N.H. van; Ramekers, D.; Gouw, D. de; Neijts, R.; Roubos, E.W.; Scheenen, W.J.; Martens, G.J.M.; Jenks, B.G.

    2012-01-01

    The pituitary melanotrope cells of the amphibian Xenopus laevis are responsible for the production of the pigment-dispersing peptide alpha-melanophore-stimulating hormone, which allows the animal to adapt its skin color to its environment. During adaptation to a dark background the melanotrope cells

  9. Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells

    DEFF Research Database (Denmark)

    Billestrup, Nils; Mitchell, R L; Vale, W;

    1987-01-01

    GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal...

  10. Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells.

    Directory of Open Access Journals (Sweden)

    Natália F Haddad

    Full Text Available Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2 and increased expression of p27(kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

  11. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  12. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  13. Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta [Niigata Univ. (Japan). School of Medicine

    1999-09-01

    To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

  14. Infantile pericardial round cell tumor

    Directory of Open Access Journals (Sweden)

    K H Sridevi

    2015-01-01

    Full Text Available Cardiac malignancies presenting in infancy are rare. Desmoplastic small round cell tumor (DSRCT is a rare occurrence in this age group. No case of intrapericardial DSRCT has been reported in the literature in infants.

  15. Long-term follow-up of patients with pituitary macroadenomas after postoperative radiation therapy. Analysis of tumor control and functional outcome

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, T.; Jakse, G.; Kapp, K.S.; Mayer, R. [Medical Univ. of Graz (Austria). Dept. of Therapeutic Radiology and Oncology; Stiegler, C. [Medical Univ. of Graz (Austria). Div. of Endocrinology and Nuclear Medicine; Quehenberger, F. [Medical Univ. of Graz (Austria). Inst. for Medical Informatics, Statistics and Documentation; Feigl, G.C. [Regensburg Univ. (Germany). Dept. of Neurosurgery; Mokry, M. [Medical Univ. of Graz (Austria). Dept. of Neurosurgery; Langsenlehner, U. [Medical Univ. of Graz (Austria). Div. of Oncology

    2007-05-15

    Purpose: Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas. Patients and Methods: In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46-54 Gy). Results: After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39-20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy. Conclusion: Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy. (orig.)

  16. Long-term follow-up of patients with pituitary macroadenomas after postoperative radiation therapy: analysis of tumor control and functional outcome.

    Science.gov (United States)

    Langsenlehner, Tanja; Stiegler, Claudia; Quehenberger, Franz; Feigl, Günther C; Jakse, Gabi; Mokry, Michael; Langsenlehner, Uwe; Kapp, Karin S; Mayer, Ramona

    2007-05-01

    Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas. In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46-54 Gy). After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39-20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy. Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy.

  17. 4-羟基他莫昔芬对泌乳素腺瘤GH3细胞PTTG表达的影响%Effect of 4-hydroxytamoxifen on the expression of pituitary tumor transforming gene in GH3 prolactinonm cells

    Institute of Scientific and Technical Information of China (English)

    崔友强; 汪建军; 滕良珠; 孔建新; 李猛; 郭建; 孙金龙

    2009-01-01

    目的 探讨雌激素受体拮抗剂4-羟基他莫昔芬(OHTam)对泌乳素腺瘤GH3细胞中垂体瘤转化基因(PTTG)表达的影响. 方法采用逆转录多聚酶链式反应(RT-PCR)和Westernblot法,测定GH3细胞中PTTG mRNA和PTTG蛋白表达.在去激素培养条件下观察不同浓度的4-羟基他莫昔芬(OHTam)和雌二醇(E2)对细胞生长速度、PTTG mRNA和PTTG蛋白表达水平的影响.结果 GH3细胞在去激素环境下细胞生长明显减慢,低浓度E2(1×10mol/L)可促进其生长,OHTam(1×10mol/L)可抑制E2(1×10mol/L)的生长刺激作用;GH3细胞中存在PTTGmRNA和PTTG蛋白的表达,且OHTam(1×10mol/L)可抑制它们的表达水平.结论泌乳素腺瘤GH3细胞的生长具有雌激素依赖性,应用雌激素受体拮抗剂OHTam能抑制GH3细胞生长和PTTG原癌基因的表达水平.%Objective To investigate the effect of 4-hydroxytamoxifen on the expression of pituitary tumor transforming gene (PTTG) in GH3 prolactinoma cells. Methods RT-PCR and Western blotting were employed to detect the expressions of PTTG mRNA and protein in human GH3 prolaetinoma cells. Different concentrations of estradiol (E2) or 4-hydroxytamoxifen (OHTam) were addedl into the hormone-depleted medium, and the viable cell number and expression levels of PTTG mRNA and protein were measured. Results The growth of OH3 prolaetinoma cells was significantly inhibited in hormone-depleted medium. E2 at a concentration of 1×10 mol/L obviously promoted the cell growth, the effect of which was inhibited by the application of OHTam (1×10 mol/L) to cause slowed cell growth. The expressions of PTTG at both the mRNA and protein levels were detected in detected in untreated GH3 prolactinoma cells, and OHTam at the concentration of 1×10 mol/L significantly inhibited their expressions. Conclusion The growth of GH3 cells is estrogen-dependant and can be inhibited by estrogen antagonist OHTam, which also results in reduced expression of PTTG gene in the cells.

  18. Pathobiology and oncogenesis of pituitary corticotroph adenomas in dogs

    NARCIS (Netherlands)

    Hanson, J.M.

    2007-01-01

    Pituitary-dependent hyperadrenocorticism (PDH) or Cushing's disease is a common endocrinopathy in the elderly dog caused by a pituitary adrenocorticotrophic hormone (ACTH) producing tumor (corticotroph adenoma) of unknown pathogenesis. Surgical removal of the pituitary tumor is applied as routine

  19. Central diabetes insipidus: Is it Langerhans cell histiocytosis of the pituitary stalk? A diagnostic pitfall.

    NARCIS (Netherlands)

    Prosch, H.; Grois, N.; Bökkerink, J.P.M.; Prayer, D.; Leuschner, I.; Minkov, M.; Gadner, H.

    2006-01-01

    Central diabetes insipidus (CDI) is a rare disorder that may be caused by a variety of diseases. In pediatric and adolescent patients the most common causes for CDI are Langerhans cell histiocytosis (LCH) and germinoma. To avoid a potentially hazardous biopsy of the hypothalamic pituitary region it

  20. Evolving radiological features of hypothalamo-pituitary lesions in adult patients with Langerhans cell histiocytosis (LCH)

    Energy Technology Data Exchange (ETDEWEB)

    Makras, P. [Athens General Hospital, Department of Endocrinology and Diabetes, Athens (Greece); Athens General Hospital, Department of Radiology, Athens (Greece); Samara, C.; Antoniou, M.; Nikolakopoulou, Z. [Athens Hospital, 9. Pulmonary Department, Athens (Greece); Zetos, A. [General Hospital, Department of Pathology, Athens (Greece); Papadogias, D.; Piaditis, G.; Kaltsas, G.A. [Athens General Hospital, Department of Endocrinology and Diabetes, Athens (Greece); Toloumis, G. [Athens General Hospital, Department of Radiology, Athens (Greece); Andreakos, E.; Kontogeorgos, G.

    2006-01-01

    Langerhans cell histiocytosis (LCH) is a rare, systemic disease caused by monoclonal expansion of dendritic cells that shows a particular predilection for the hypothalamic-pituitary system (HPS). We studied the function (anterior and posterior pituitary hormonal secretion) and morphology using magnetic resonance imaging (MRI) of the HPS in 17 adult patients (seven males, median age 35 years, range 18-59 years) with multisystem LCH. We also evaluated the evolution of structural HPS abnormalities in relation to pituitary function and response to treatment in 12 of these patients during a median follow-up period of 3.75 years (range 1.5-10 years). Of the 17 patients, 14 (82%) had abnormal HPS imaging, and 12 (70%) had more than one area involved. Lack of the bright spot of the posterior pituitary lobe was typically found in all patients with the diagnosis of diabetes insipidus (DI). Eight patients (47%) had infundibular enlargement, six (35%) pituitary infiltration, four (24%) partially or completely empty sella, three (18%) hypothalamic involvement, and two (12%) infundibular atrophy. DI was found in 16 patients (94%) and anterior pituitary hormonal deficiency (APHD) in 10 patients (59%); two patients had single (12%) and 8 (47%) multiple APHD. During the follow-up period there was improvement of the initially demonstrated HPS pathology in seven (47%) patients, and five (33%) of them had received at least one form of treatment. APHD and DI persisted in all patients except in one in whom established gonadotrophin deficiency recovered. In summary, DI and APHD are very common in patients with multisystem LCH and are almost always associated with abnormal HPS imaging. (orig.)

  1. The Marine Metabolite SZ-685C Induces Apoptosis in Primary Human Nonfunctioning Pituitary Adenoma Cells by Inhibition of the Akt Pathway in Vitro

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-03-01

    Full Text Available Nonfunctioning pituitary adenoma (NFPA is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403 which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.

  2. Expression Analysis of the Hippo Cascade Indicates a Role in Pituitary Stem Cell Development

    Directory of Open Access Journals (Sweden)

    Emily J Lodge

    2016-03-01

    Full Text Available The pituitary gland is a primary endocrine organ that controls major physiological processes. Abnormal development or homeostatic disruptions can lead to human disorders such as hypopituitarism or tumours. Multiple signalling pathways, including WNT, BMP, FGF and SHH regulate pituitary development but the role of the Hippo-YAP1/TAZ cascade is currently unknown. In multiple tissues, the Hippo kinase cascade underlies neoplasias; it influences organ size through the regulation of proliferation and apoptosis, and has roles in determining stem cell potential. We have used a sensitive mRNA in situ hybridisation method (RNAscope to determine the expression patterns of the Hippo pathway components during mouse pituitary development. We have also carried out immunolocalisation studies to determine when YAP1 and TAZ, the transcriptional effectors of the Hippo pathway, are active. We find that YAP1/TAZ are active in the stem/progenitor cell population throughout development and at postnatal stages, consistent with their role in promoting the stem cell state. Our results demonstrate for the first time the collective expression of major components of the Hippo pathway during normal embryonic and postnatal development of the pituitary gland.

  3. Adipokines (Leptin, Adiponectin, Resistin) Differentially Regulate All Hormonal Cell Types in Primary Anterior Pituitary Cell Cultures from Two Primate Species.

    Science.gov (United States)

    Sarmento-Cabral, André; Peinado, Juan R; Halliday, Lisa C; Malagon, María M; Castaño, Justo P; Kineman, Rhonda D; Luque, Raúl M

    2017-03-06

    Adipose-tissue (AT) is an endocrine organ that dynamically secretes multiple hormones, the adipokines, which regulate key physiological processes. However, adipokines and their receptors are also expressed and regulated in other tissues, including the pituitary, suggesting that locally- and AT-produced adipokines might comprise a regulatory circuit that relevantly modulate pituitary cell-function. Here, we used primary pituitary cell-cultures from two normal nonhuman-primate species [Papio-anubis/Macaca-fascicularis] to determine the impact of different adipokines on the functioning of all anterior-pituitary cell-types. Leptin and resistin stimulated GH-release, a response that was blocked by somatostatin. Conversely, adiponectin decreased GH-release, and inhibited GHRH-, but not ghrelin-stimulated GH-secretion. Furthermore: 1) Leptin stimulated PRL/ACTH/FSH- but not LH/TSH-release; 2) adiponectin stimulated PRL-, inhibited ACTH- and did not alter LH/FSH/TSH-release; and 3) resistin increased ACTH-release and did not alter PRL/LH/FSH/TSH-secretion. These effects were mediated through the activation of common (AC/PKA) and distinct (PLC/PKC, intra-/extra-cellular calcium, PI3K/MAPK/mTOR) signaling-pathways, and by the gene-expression regulation of key receptors/transcriptional-factors involved in the functioning of these pituitary cell-types (e.g. GHRH/ghrelin/somatostatin/insulin/IGF-I-receptors/Pit-1). Finally, we found that primate pituitaries expressed leptin/adiponectin/resistin. Altogether, these and previous data suggest that local-production of adipokines/receptors, in conjunction with circulating adipokine-levels, might comprise a relevant regulatory circuit that contribute to the fine-regulation of pituitary functions.

  4. Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3

    Science.gov (United States)

    Grindeland, R.; Hymer, W. C.; Farrington, M.; Fast, T.; Hayes, C.; Motter, K.; Patil, L.; Vasques, M.

    1987-01-01

    The effect of exposure to microgravity on pituitary gland was investigated by examining cells isolated from anterior pituitaries of rats flown on the 7-day Spacelab 3 mission and, subsequently, cultured for 6 days. Compared with ground controls, flight cells contained more intracellular growth hormone (GH); however, the flight cells released less GH over the 6-day culture period and after implantation into hypophysectomized rats than did the control cells. Compared with control rats, glands from large rats (400 g) contained more somatotrophs (44 percent compared with 37 percent in control rats); small rats (200 g) showed no difference. No major differences were found in the somatotroph ultrastructure (by TEM) or in the pattern of the immunoactive GH variants. However, high-performance liquid chromatography fractionation of culture media indicated that flight cells released much less of a biologically active high-molecular weight GH variant, suggesting that space flight may lead to secretory dysfunction.

  5. Tumor consistency of pituitary macroadenomas: predictive analysis on the basis of imaging features with contrast-enhanced 3D FIESTA at 3T.

    Science.gov (United States)

    Yamamoto, J; Kakeda, S; Shimajiri, S; Takahashi, M; Watanabe, K; Kai, Y; Moriya, J; Korogi, Y; Nishizawa, S

    2014-02-01

    Preoperative evaluation of pituitary macroadenoma tumor consistency is important for neurosurgery. Thus, we aimed to retrospectively assess the role of contrast-enhanced FIESTA in predicting the tumor consistency of pituitary macroadenomas. Twenty-nine patients with pituitary macroadenomas underwent conventional MR imaging sequences and contrast-enhanced FIESTA before surgery. Two neuroradiologists assessed the contrast-enhanced FIESTA, contrast-enhanced T1WI, and T2WI. On the basis of surgical findings, the macroadenomas were classified by the neurosurgeons as either soft or hard. Finally, Fisher exact probability tests and unpaired t tests were used to compare predictions on the basis of the MR imaging findings with the tumor consistency, collagen content, and postoperative tumor size. The 29 pituitary macroadenomas were classified as either solid or mosaic types. Solid type was characterized by a homogeneous pattern of tumor signal intensity without intratumoral hyperintense dots, whereas the mosaic type was characterized by many intratumoral hyperintense dots on each MR image. Statistical analyses revealed a significant correlation between tumor consistency and contrast-enhanced FIESTA findings. Sensitivity and specificity were higher for contrast-enhanced FIESTA (1.00 and 0.88-0.92, respectively) than for contrast-enhanced T1WI (0.80 and 0.25-0.33, respectively) and T2WI (0.60 and 0.38-0.54, respectively). Compared with mosaic-type adenomas, solid-type adenomas tended to have a hard tumor consistency as well as a significantly higher collagen content and lower postoperative tumor size. Contrast-enhanced FIESTA may provide preoperative information regarding the consistency of macroadenomas that appears to be related to the tumor collagen content.

  6. In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing.

    Science.gov (United States)

    Jomaa, Barae; Aarts, Jac M M J G; de Haan, Laura H J; Peijnenburg, Ad A C M; Bovee, Toine F H; Murk, Albertinka J; Rietjens, Ivonne M C M

    2013-01-01

    This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

  7. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, S.L.; Ham, R.G.; Stampfer, M.R.

    1984-09-01

    A serum-free medium with bovine pituitary extract as the only undefined supplement has been developed for long-term culture of human mammary epithelial cells. This medium supports serial subculture of normal cells for 10-20 passages (1:10 splits) without conditioning or special substrates, and it supports rapid clonal growth with plating efficiencies up to 35%. It consists of an optimized basal nutrient medium, (MCDB 170, supplemented with insulin, hydrocortisone, epidermal growth factor, ethanolamine, phosphoethanolamine, and bovine pituitary extract. Replacement of pituitary extract with prostaglandin E/sub 1/ and ovine prolactin yields a defined medium that supports rapid clonal growth and serial subculture for three of four passages. Cultures initiated in these media from normal reduction mammoplasty tissue remain diploid and maintain normal epithelia morphology, distribution of cell-associated fibronectin, expression of keratin fibrils, and a low level of expression of milk fat globule antigen. Large cell populations can now be generated and stored frozen, permitting multiple experiments over a period of time with cells from a single donor. These media greatly extend the range of experiments that can be performed both conveniently and reproducibly with cultured normal and tumor-derived human mammary epithelial cells. 31 references, 3 figures, 4 tables.

  8. Effect of atrial natriuretic peptide on gonadotropin release in superfused rat pituitary cells.

    OpenAIRE

    Horvath, J; Ertl, T.; Schally, A V

    1986-01-01

    Cardiac atrial muscle cells produce a polypeptide hormone that plays a role in the control of water and electrolyte balance and blood pressure. The circulating form of this hormone is the atrial natriuretic peptide (ANP), which contains 28 amino acids. Various immunohistochemical studies have shown that ANP is present in many areas of the central nervous system, including the median eminence. In our studies, we investigated the effect of ANP in a superfused rat pituitary cell system. When ANP...

  9. Pituitary Apoplexy Presented with Optic Neuritis

    Directory of Open Access Journals (Sweden)

    Mahsa Owji

    2013-07-01

    Full Text Available The patient is a 40-years-old woman presented with visual loss in the right eye since two days ago. The patient complained of headache with gradual onset in the right parietal area since 2 years ago. The headache pattern did not alter.The left eye was normal but the vision in the right eye was 50 cm finger counting. Marcus Gunn pupil could be observed during swinging-flashlight test in the right eye. According to these findings, the first diagnosis was optic neuritis which was corroborated with visual evoked potential (the latency of P100 was 122. According to magnetic resonance imaging (MRI, there was a big cystic tumor in sella turcica extended to the suprasellar region (Figure 1-A. It had a large liquid component. Optic chiasm was under pressure and was displaced (Figure 1-B. A faint enhancement was seen after the injection (Figure 1-C.The patient was operated with the transnasal-transsphenoidal approach. Blood and fibrin were among the small monomorphic round cells andfibro-connective tissue of the pituitary gland. Considering the bleeding inside the pituitary tumor, the final diagnosis was pituitary apoplexy. After recovery from the operation the symptoms were removed.Pituitary apoplexy presents with headache, loss of vision, ophthalmoplegia, and mental alterations which is caused by infarction or sudden bleeding inside the pituitary tumor.1In our review of literature, 3 patients afflicted with pituitary apoplexy presented with optic neuritis were reported.In a study conducted by Petersen et al., all three patients referred to them suffered from unilateral visual loss and headache. They were examined with the early diagnosis of optic neuritis. After taking a Brain Computerized tomography (CT scan, pituitary adenoma together with the formation of cyst were detected in patients. After transsphenoidal adenomectomy, the patient regained full vision. Therefore, the correct diagnosis of these patients, who had been incorrectly diagnosed with

  10. Impact of environmental chemicals on the thyroid hormone function in pituitary rat GH3 cells

    DEFF Research Database (Denmark)

    Ghisari, Mandana; Bonefeld-Jørgensen, Eva

    2005-01-01

    -nonylphenol, 4-octylphenol), pesticides (prochloraz, iprodion, chlorpyrifos), PCB metabolites (OH-PCB 106, OH-PCB 121, OH-PCB 69) and brominated flame-retardants (tetrabromobisphenol A). The ED potential of a chemical was determined by its effect on the cell proliferation of TH-dependent rat pituitary GH3 cell...... line. All tested chemicals significantly interfered with the cell proliferation alone or upon co-treatment with T3. The growth of GH3 cells was stimulated by all tested chemicals, but 4-n-nonylphenol, 4-octylphenol, prochloraz and iprodion elicited an inhibitory effect on cell growth. In conclusion...

  11. Human pituitary tissue secretes a potent growth factor for chondrocyte proliferation.

    Science.gov (United States)

    Kasper, S; Friesen, H G

    1986-01-01

    We report the secretion from human pituitary tumor fragments in organ culture of a potent mitogen for chondrocyte proliferation. Primary human pituitary cell and organ cultures were established from pituitary fragments obtained from patients with acromegaly, prolactinomas, and nonfunctional adenomas. The conditioned culture medium contained a mitogenic factor(s) that stimulated rabbit fetal chondrocyte proliferation, causing up to an 8-fold increase in cell number when added to Ham's F-10 medium in the presence of 10% fetal bovine serum. Blood leaking into the surgical field after the adenomectomy is known to contain very high concentrations of pituitary hormones. Serum samples, obtained from this venous "ooze" collected at the site of pituitary surgery, also were found to contain chondrocyte growth-promoting activity. Some venous serum samples stimulated chondrocyte proliferation in a dose-dependent manner down to a 1:10 dilution of 1 microliter serum, indicating that the material being secreted was very potent indeed. Gel filtration on Sephadex G-100 and analytical gel isoelectric focusing of culture media or serum samples from the pituitary fossa demonstrated that the growth factor secreted from the pituitary tumor fragments as well as from the venous serum is similar, if not identical, to chondrocyte growth factor (mol wt, 43,000; pI 7.6-7.9) purified from human pituitaries collected at autopsy. These results suggest that the chondrocyte growth-promoting factor(s) may not only be secreted by pituitary tumor fragments but by normal human pituitary tissue as well.

  12. MicroRNAs in Human Pituitary Adenomas

    Directory of Open Access Journals (Sweden)

    Xu-Hui Li

    2014-01-01

    Full Text Available MicroRNAs (miRNAs are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers.

  13. Pituitary Gland Disorders Overview

    Science.gov (United States)

    ... reducing the amount of water lost in urine Oxytocin – causes milk to flow from the breasts in breastfeeding women, and may also help labor to progress Pituitary Tumors The most frequent type ...

  14. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

    Directory of Open Access Journals (Sweden)

    Carolina Cristina

    2014-01-01

    Full Text Available The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives.

  15. [Practice guideline for diagnosis and treatment of craniopharyngioma and parasellar tumors of the pituitary gland].

    Science.gov (United States)

    Venegas, Eva; Concepcion, Blanco; Martin, Tomas; Soto, Alfonso

    2015-01-01

    Craniopharyngiomas are rare, locally aggressive epithelial tumors usually located in the sellar and suprasellar region. Diagnosis of craniopharyngioma is usually suggested by clinical and radiological findings that should be confirmed histologically. Surgery is the treatment of choice for most patients. The goal of surgery is to relieve compressive symptoms and to remove as much tumor as safely possible. Radiation therapy is the usual treatment to control postoperative tumor remnants and local recurrences. Parasellar lesions are low prevalent lesions and include neoplastic, inflammatory, infectious, developmental, and vascular diseases. Both their diagnosis and treatment depend on the type of lesion. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  16. Microenvironments Dictating Tumor Cell Dormancy

    Science.gov (United States)

    Bragado, Paloma; Sosa, Maria Soledad; Keely, Patricia; Condeelis, John

    2012-01-01

    The mechanisms driving dormancy of disseminated tumor cells (DTCs) remain largely unknown. Here, we discuss experimental evidence and theoretical frameworks that support three potential scenarios contributing to tumor cell dormancy. The first scenario proposes that DTCs from invasive cancers activate stress signals in response to the dissemination process and/or a growth suppressive target organ microenvironment inducing dormancy. The second scenario asks whether therapy and/or micro-environmental stress conditions (e.g. hypoxia) acting on primary tumor cells carrying specific gene signatures prime new DTCs to enter dormancy in a matching target organ microenvironment that can also control the timing of DTC dormancy. The third and final scenario proposes that early dissemination contributes a population of DTCs that are unfit for immediate expansion and survive mostly in an arrested state well after primary tumor surgery, until genetic and/or epigenetic mechanisms activate their proliferation. We propose that DTC dormancy is ultimately a survival strategy that when targeted will eradicate dormant DTCs preventing metastasis. For these non-mutually exclusive scenarios we review experimental and clinical evidence in their support. PMID:22527492

  17. Mechanisms of tumor cell necrosis.

    Science.gov (United States)

    Proskuryakov, Sergey Y; Gabai, Vladimir L

    2010-01-01

    Until recently, necrosis, unlike apoptosis, was considered as passive and unregulated form of cell death. However, during the last decade a number of experimental data demonstrated that, except under extreme conditions, necrosis may be a well-regulated process activated by rather specific physiological and pathological stimuli. In this review, we consider mechanisms and the role of necrosis in tumor cells. It became recently clear that the major player in necrotic cascade is a protein kinase RIP1, which can be activated by number of stumuli including TNF, TRAIL, and LPS, oxidative stress, or DNA damage (via poly-ADP-ribose polymerase). RIP1 kinase directly (or indirectly via another kinase JNK) transduces signal to mitochondria and causes specific damage (mitochondrial permeability transition). Mitochondrial collapse activates various proteases (e.g., calpains, cathepsin) and phospholipases, and eventually leads to plasma membrane destruction, a hallmark of necrotic cell death. Necrosis, in contrast to apoptosis, usually evokes powerful inflammatory response, which may participate in tumor regression during anticancer therapy. On the other hand, excessive spontaneous necrosis during tumor development may lead to more aggressive tumors due to stimulatory role of necrosis-induced inflammation on their growth.

  18. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  19. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    Science.gov (United States)

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  20. Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects?

    Science.gov (United States)

    Xekouki, Paraskevi; Stratakis, Constantine A

    2012-12-01

    Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney-Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity at the SDHD locus, indicating the possibility that SDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.

  1. The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors.

    Science.gov (United States)

    Di Ieva, A; Grizzi, F; Ceva-Grimaldi, G; Aimar, E; Serra, S; Pisano, P; Lorenzetti, M; Tancioni, F; Gaetani, P; Crotti, F; Tschabitscher, M; Matula, C; Rodriguez Y Baena, R

    2010-06-01

    In geometrical terms, tumor vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic, together with the highly variable vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological features have now been well established, quantitative analyses of neovascularity in two-dimensional histological sections still fail to view tumor architecture in non-Euclidean terms, and this leads to errors in visually interpreting the same tumor, and discordant results from different laboratories. A review of the literature concerning the application of microvessel density (MVD) estimates, an Euclidean-based approach used to quantify vascularity in normal and neoplastic pituitary tissues, revealed some disagreements in the results and led us to discuss the limitations of the Euclidean quantification of vascularity. Consequently, we introduced fractal geometry as a better means of quantifying the microvasculature of normal pituitary glands and pituitary adenomas, and found that the use of the surface fractal dimension is more appropriate than MVD for analysing the vascular network of both. We propose extending the application of this model to the analysis of the angiogenesis and angioarchitecture of brain tumors.

  2. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  3. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... Germ Cell Tumors Treatment Extragonadal Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  4. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  5. Studies on prolactin-secreting cells in aging rats of different strains. I. Alterations in pituitary histology and serum prolactin levels as related to ageing.

    NARCIS (Netherlands)

    Putten, van L.J.A.; Zwieten, van M.J.; Mattheij, J.A.M.; Kemenade, J.A.M.

    1988-01-01

    Serum PRL levels and histologically tumor-free pituitary glands of 91 aging rats of the BN/BiRij strain, the WAG/Rij strain and their F1 hybrid were studied. In rats with pituitary glands without signs of hyperplasia, serum PRL levels were, in comparison to rats of 15-24 months, increased 25-29-mont

  6. High Population Density of Juvenile Chum Salmon Decreased the Number and Sizes of Growth Hormone Cells in the Pituitary

    OpenAIRE

    Salam, Md. Abdus; Ota, Yuki; Ando, Hironori; Fukuwaka, Masa-aki; Kaeriyama, Masahide; Urano, Akihisa

    1999-01-01

    Juveniles of chum salmon (Oncorhynchus keta) held at high population density were apparently smaller than those held at medium and low population densities. The effects of high population density on pituitary growth hormone (GH) cells in juvenile chum salmon were examined using immunocytochemical and in situ hybridization techniques. The ratio of GH-immunoreactive (ir) area to the whole pituitary was almost constant in all of the high, medium and low population density groups, although the nu...

  7. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan

    2017-01-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors...... on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs....

  8. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  9. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  10. Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness in pituitary macroadenomas without optic chiasmal compression

    Science.gov (United States)

    Cennamo, G; Auriemma, R S; Cardone, D; Grasso, L F S; Velotti, N; Simeoli, C; Di Somma, C; Pivonello, R; Colao, A; de Crecchio, G

    2015-01-01

    Purpose The aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression. Patients and methods Twenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. Results Patients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in controls. The average GCC (r=0.306, P=0.046) significantly correlated with the presence of arterial hypertension. OCT parameters did not differ significantly between patients with a tumour volume above the median and those with a tumour volume below the median. Conclusion Pituitary macroadenomas, even in the absence of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours. PMID:25853400

  11. Cushing-type ectopic pituitary adenoma with unusual pathologic features

    Directory of Open Access Journals (Sweden)

    Kristopher T. Kimmell, MD

    2014-06-01

    Full Text Available Ectopic pituitary adenomas comprise, by varying reports, approximately 1-2% of all pituitary adenomas. They are often located in the nasopharyngeal region associated with the pharyngeal pituitary. The location and pathologic features of these masses make them atypical when compared with intrasellar pituitary adenomas. A 54-year-old man presented with vertebral compression fracture and physical stigmata of Cushing’s disease. Biochemical testing confirmed hypercortisolemia responsive to high dose dexamethasone suppression. MRI of the head demonstrated an enhancing mass in the posterior aspect of the sphenoid sinus not involving the sella turcica. Endoscopic biopsy followed by resection confirmed this mass to be a pituitary adenoma with unusual pathologic features. Most notably, the tumor cells demonstrated large, eosinophilic, vacuolated cytoplasm. Immunohistochemical profile of the tumor was typical of an ACTH secreting tumor, notably with positivity for ACTH. The patient did well from his surgery. Post-operatively his serum cortisol level normalized and he remains in chemical remission one year after surgery. Ectopic pituitary adenomas are an unusual manifestation of hormonally active pituitary neoplastic disease. Their atypical clinical presentations, location, and pathologic features can make them a diagnostic challenge. Clinicians should be aware of these entities, especially when considering differential diagnosis for a mass in the sphenoid sinus and nasopharyngeal region.

  12. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    Science.gov (United States)

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism.

  13. Experimental Modification of Rat Pituitary Prolactin Cell Function During and After Spaceflight

    Science.gov (United States)

    Hymer, W. C.; Salada, T.; Avery, L.; Grindeland, R. E.

    1996-01-01

    Experimental modification of rat pituitary prolactin cell function during and after spaceflight. This study was done to evaluate the effects of microgravity on prolactin (PRL) cells of the male rat pituitary gland. We used the identical passive closed-vial cell culture system that was described for the culture of growth hormone cells (W C. Hymer, R. E. Grindeland, T. Salada, P. Nye, E. Grossman, and R Lane). After an 8-day spaceflight, all flight media (containing released PRL), as well as extracts (containing intracellular PRL), contained significantly lower amounts of immunoreactive PRL than their corresponding ground control samples. On the other hand, these same samples, when assessed for their biological activities by two different in vitro lymphocyte assays, yielded disparate results that may reflect posttranslational modifications to the hormone molecule. Other data showed that: (1) the apparent molecular weights of released PRL molecules were not altered by microgravity; but (2) the region from which the PRL cells came (dorsal or ventral) made a significant difference in the amount and activity of PRL released from the flight cells. Because there is much current interest in the role that PRL may play in the regulation of the immune system and because changes in both cellular and humoral immunity accompany spaceflight, this study could help define future microgravity research in this area.

  14. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma.

    Science.gov (United States)

    Lee, Cheng-Chi; Chen, Chung-Ming; Lee, Shih-Tseng; Wei, Kuo-Chen; Pai, Ping-Ching; Toh, Cheng-Hong; Chuang, Chi-Cheng

    2015-11-05

    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement.

  15. Hypothalamic corticotropin-releasing factor immunoreactivity is reduced during induction of pituitary tumors by chronic estrogen treatment

    Energy Technology Data Exchange (ETDEWEB)

    Haas, D.A.; Borgundvaag, B.; Sturtridge, W.C.; George, S.R.

    1987-11-02

    The role that estrogen plays in the regulation of corticotropin-releasing factor (CRF) is not known. A radioimmunoassay specific for rat CRF was utilized to measure the CRF-like immunoreactivity (CRF-ir) in the hypothalamus of ovariectomized rats treated with estradiol for periods up to 12 weeks. Compared to ovariectomized controls, estradiol treatment resulted in significantly reduced CRF-ir after 3 and 12 weeks, although no significant change was seen after 8 weeks. Anterior pituitary (AP) weight was greatly increased by estradiol treatment at all time points studied. Bromocriptine treatment for the last 3 weeks of the 12-week period, or removal of estradiol for 3 weeks after 9 weeks of treatment did not reverse the changes in CRF-ir even though significant regressions of tumor size was achieved. There was no correlation between AP weight and CRF-ir in individual animals. These data show that chronic treatment with estrogen reduced hypothalamic CRF-ir content. Neither a direct estrogenic effect or an indirect effect mediated through alterations in the adenohypophysis could be ruled out. 21 references, 3 figures.

  16. [Effect of transcutaneous acupoint electric stimulation on perioperative intravenous anesthesia in patients of transsphenoidal pituitary tumor resection].

    Science.gov (United States)

    Chen, Xue; Wang, Bao-Guo; Li, Jin; An, Li-Xin

    2013-08-01

    To observe the impacts of transcutaneous acupoint electric stimulation on hemodynamics, anesthetic and relevant complications in patients of transsphenoidal pituitary tumor resection (TPTR). Ninety cases of the selective TPTR were randomized into a transcutaneous acupoint electric stimulation group (group T), a sham-acupoint group (group S) and a control group (group C); 30 cases in each one. In group T, the transcutaneous acupoint electric stimulation at Hegu (LI 4), Waiguan (TE 5), Jinmen (BL 63), Taichong (LR 3), Zusanli (ST 36) and Qiuxu (GB 40). In group S, the transcutaneous acupoint electric stimulation was applied to the sham-acupoints. In group C, the acupoints selected were same as those in group T, but the electrode pads were just attached on the related points with no-electric stimulation. The electric stimulation lasted from analgesic induction till the end of the operation. The endotracheal intubation was done under the induction by propofol, fentanyl and vecuronium bromide. Propofol and remifentanil were maintained till the end of operation. Blood pressure, heart rate, bispectral index (BIS) value, anesthetic and postoperative recovery situation were recorded. The hemodynamics maintained stably in each group. In group T, the mean arterial pressure 1 min after intubation, after extubation and during directional force recovery was all lower than the other two groups respectively (all Pelectric stimulation improves the stability of hemodynamics in perioperative stage, reduces the intraoperative opi oids dosages and improves the quality of anesthetic recovery.

  17. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma.

  18. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  19. Adiponectin regulates ACTH secretion and the HPAA in an AMPK-dependent manner in pituitary corticotroph cells.

    Science.gov (United States)

    Chen, Maopei; Wang, Zhiquan; Zhan, Ming; Liu, Ruixin; Nie, Aifang; Wang, Jiqiu; Ning, Guang; Ma, Qinyun

    2014-03-05

    It is known that adipokines can regulate the hypothalamic-pituitary-adrenal axis (HPAA). In this study, we confirmed that adiponectin regulates the HPAA by affecting pituitary corticotroph cells. Using RT-PCR and immunofluorescence, we determined that adiponectin receptors were expressed in pituitary corticotroph tumour cells (AtT-20 cells and human corticotroph tumours). Adiponectin stimulated calcium influx and increased basal ACTH secretion without affecting corticotrophin-releasing hormone (CRH)-stimulated ACTH secretion, which was most likely due to the expression of adiponectin repressing CRH receptor 1 (CRHR1). Adiponectin also acutely stimulated ACTH release in primary culture pituitary cells. Lastly, adiponectin directly phosphorylated 5' AMP-activated protein kinase (AMPK) in AtT-20 cells. The effects of adiponectin were mimicked by AICAR, which was blocked by compound C. Taken together, our results suggested that adiponectin stimulated ACTH secretion and down-regulated CRHR1, possibly via an AMPK-dependent mechanism in pituitary corticotroph cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. The mechanism of mimecan transcription induced by glucocorticoid in pituitary corticotroph cells.

    Science.gov (United States)

    Zhang, Xiao Na; Xue, Li Qiong; Jiang, He; Yang, Shao Ying; Song, Huai Dong; Ma, Qin Yun

    2012-01-01

    Mimecan, a secretary protein that is expressed in mouse and human pituitary corticotroph cells, is up-regulated by glucocorticoids (GC) in the corticotroph cells via classical glucocorticoid receptor (GR) pathways. In this study, we further explore the GC mechanism for mimecan expression in these cells. Five putative GR response elements (GREs) were identified in ~2 kb of the mimecan promoter by programme analysis. An EMSA assay further indicated that these putative GREs were bound by the GR. Moreover, three proximal GREs are conserved between species. Although luciferase assays showed that the -1474/+43 region of the mimecan promoter achieved the highest expression of mimecan, the -803/+43 mimecan promoter region was sufficient for the GC-mediated expression of mimecan. The mutations of three conserved GREs located in the -1474/+43 mimecan promoter region did not affect mimecan transcription, which suggests that the effects of GC on mimecan are independent of the GREs in the promoter. In addition, cycloheximide, a protein synthesis inhibitor, blocked GC-induced mimecan expression in AtT-20 cells. Taken together, these results suggest that, although there are 3-5 GREs in the mimecan promoter, GC may regulate mimecan transcription indirectly through the synthesis of intermediate proteins and not through the GREs in pituitary corticotroph cells.

  1. Expression of Neuropeptide Y in Human Pituitary Adenoma

    Institute of Scientific and Technical Information of China (English)

    Laizhao Chen; Jingjian Ma; Anchao Zheng; Honggang Zheng

    2006-01-01

    OBJECTIVE Neuropeptid e Y (NPY) acts as a neuroendocrine modulator in the anterior pituitary, and NPY mRNA and NPY-immunoreactivity have been detected in normal human anterior pituitaries. However, only a few studies of NPY expression in human pituitary adenomas have been published. Our study was conducted to determine whether or not adenomatous cells express NPY, to investigate the relationship between NPY expression and the subtypes of pituitary adenoma and to explore the clinical significance of NPY.METHODS The study included tissues from 58 patients with pituitary adenomas who underwent surgery because of their clinical diagnosis.Using a highly specific anti-NPY polyclonal antibody, immunohistochemical analysis was performed on the surgically removed pituitary adenomas. Six fresh specimens also were examined using immuno-electron microscopy. NPY was labeled with colloidal gold in order to study the distribution of NPY at the subcellular level.RESULTS The NPY expression level was significantly different among subgroups of pituitary adenomas (P<0.05). NPY was immuno-detected in 58.6% of all adenomas, in 91.7% of gonadotrophic adenomas and in 14.3% of prolactinomas. NPY expression was slightly lower in invasive pituitary adenomas compared to noninvasive adenomas, but the difference was not significant (t=1.81, P>0.05). Of particular interest was the finding that vascular endothelial cells showed positive NPY expression in some pituitary adenomas. Parts of strongly positive tumor cells were seen in channels formed without endothelial cells, but which contained some red blood cells in a formation similar to so-called vasculogenic mimicry. Immuno-electron microscopy demonstrated that 4 of the 6 fresh specimens displayed positive NPY staining with a high density of gold particles located mainly in the secretory granulas. In addition, gold particles were sparsely detected in the rough endoplasmic reticulum and cell matrix.CONCLUSION NPY exists in pituitary adenomas

  2. Control of anterior pituitary cell excitability by calcium-activated potassium channels.

    Science.gov (United States)

    Shipston, Michael J

    2017-06-05

    In anterior pituitary endocrine cells, large (BK), small (SK) and intermediate (IK) conductance calcium activated potassium channels are key determinants in shaping cellular excitability in a cell type- and context-specific manner. Indeed, these channels are targeted by multiple signaling pathways that stimulate or inhibit cellular excitability. BK channels can, paradoxically, both promote electrical bursting as well as terminate bursting and spiking dependent upon intrinsic BK channel properties and proximity to voltage gated calcium channels in somatotrophs, lactotrophs and corticotrophs. In contrast, SK channels are predominantly activated by calcium released from intracellular IP3-sensitive calcium stores and mediate membrane hyperpolarization in cells including gonadotrophs and corticotrophs. IK channels are predominantly expressed in corticotrophs where they limit membrane excitability. A major challenge for the future is to determine the cell-type specific molecular composition of calcium-activated potassium channels and how they control anterior pituitary hormone secretion as well as other calcium-dependent processes. Copyright © 2017. Published by Elsevier B.V.

  3. Modulations of prolactin and growth hormone gene expression and chromatin structure in cultured rat pituitary cells.

    OpenAIRE

    Levy-Wilson, B

    1983-01-01

    I have measured the effect of hormones and other regulatory factors present in the serum component of the culture medium on the levels of growth hormone and prolactin mRNAs in rat pituitary (GH4) cells. Hybridization of cytoplasmic RNA with growth hormone or prolactin cDNA clones indicate that serum depletion reduces significantly the amount of these two mRNAs. The localization of these two genes in chromatin was also analysed using micrococcal nuclease as a probe. At intermediate levels of d...

  4. Growth hormone-releasing hormone stimulates cAMP release in superfused rat pituitary cells.

    OpenAIRE

    Horváth, J E; Groot, K. de; Schally, A V

    1995-01-01

    The release of growth hormone (GH) and cAMP was studied in superfused rat pituitary cells by infusing growth hormone-releasing hormone (GHRH) at different doses or a combination of GHRH and somatostatin 14 (SS-14). Three-minute pulses of GHRH caused a dose-dependent GH and cAMP release (effective concentration of 50% of the maximal biological effect is 0.21 nM and 52.5 nM, respectively). The lowest effective doses of GHRH in the superfusion system were 0.03 nM for GH release and 0.3 nM for cA...

  5. NK cells in the tumor microenvironment

    DEFF Research Database (Denmark)

    Larsen, Stine K; Gao, Yanhua; Basse, Per H

    2014-01-01

    The presence of natural killer (NK) cells in the tumor microenvironment correlates with outcome in a variety of cancers. However, the role of intratumoral NK cells is unclear. Preclinical studies have shown that, while NK cells efficiently kill circulating tumor cells of almost any origin...

  6. Imaging Tumor Cell Movement In Vivo

    OpenAIRE

    Entenberg, David; Kedrin, Dmitriy; Wyckoff, Jeffrey; Sahai, Erik; Condeelis, John; Segall, Jeffrey E

    2013-01-01

    This unit describes the methods that we have been developing for analyzing tumor cell motility in mouse and rat models of breast cancer metastasis. Rodents are commonly used both to provide a mammalian system for studying human tumor cells (as xenografts in immunocompromised mice) as well as for following the development of tumors from a specific tissue type in transgenic lines. The Basic Protocol in this unit describes the standard methods used for generation of mammary tumors and imaging th...

  7. The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration.

    Science.gov (United States)

    Fu, Qiuli; Gremeaux, Lies; Luque, Raul M; Liekens, Daisy; Chen, Jianghai; Buch, Thorsten; Waisman, Ari; Kineman, Rhonda; Vankelecom, Hugo

    2012-07-01

    The pituitary gland constitutes, together with the hypothalamus, the regulatory core of the endocrine system. Whether the gland is capable of cell regeneration after injury, in particular when suffered at adult age, is unknown. To investigate the adult pituitary's regenerative capacity and the response of its stem/progenitor cell compartment to damage, we constructed a transgenic mouse model to conditionally destroy pituitary cells. GHCre/iDTR mice express diphtheria toxin (DT) receptor after transcriptional activation by Cre recombinase, which is driven by the GH promoter. Treatment with DT for 3 d leads to gradual GH(+) (somatotrope) cell obliteration with a final ablation grade of 80-90% 1 wk later. The stem/progenitor cell-clustering side population promptly expands after injury, concordant with the immediate increase in Sox2(+) stem/progenitor cells. In addition, folliculo-stellate cells, previously designated as pituitary stem/progenitor cells and significantly overlapping with Sox2(+) cells, also increase in abundance. In situ examination reveals expansion of the Sox2(+) marginal-zone niche and appearance of remarkable Sox2(+) cells that contain GH. When mice are left after the DT-provoked lesion, GH(+) cells considerably regenerate during the following months. Double Sox2(+)/GH(+) cells are observed throughout the regenerative period, suggesting recovery of somatotropes from stem/progenitor cells, as further supported by 5-ethynyl-2'-deoxyuridine (EdU) pulse-chase lineage tracing. In conclusion, our study demonstrates that the adult pituitary gland holds regenerative competence and that tissue repair follows prompt activation and plausible involvement of the stem/progenitor cells.

  8. The pituitary gland of the coelacanth fish Latimeria chalumnae Smith: general structure and adenohypophysial cell types.

    Science.gov (United States)

    van Kemenade, J A; Kremers, J W

    1975-11-12

    The pituitary gland of Latimeria chalumnae is situated rostroventral to the telencephalon. The hollow pituitary stalk is bent forward and is ventrally connected to a saccus-vasculosus-like organ, rostrally to a neurointermediate lobe. The infundibular lumen protrudes far into the neurohypophysial lobules. The elongated principal part (pars cerebralis) of the pars distalis is partly embedded in a dorsal depression of the pars intermedia and caudally invaded by the neurohypophysis. It may be divided into rostral and proximal pars distalis and includes a ramified hypophysial cleft, which continues rostrally as a duct with adjacent islets of pars distalis tissue (parts of a pars buccalis). The adenohypophysis consists of cell cords and follicles. Eight tinctorial cell types can be distinguished: in the rostral islets: large basophils with acidophil globules, in the rostral pars distalis: small basophils, large basophils with amphiphil characters and erythrosin-, orange G-positive acidophils; in the proximal pars distalis: orange G-positive acidophils and small and large basophils, having similar staining properties; in the pars intermedia: one amphiphil cell type.

  9. Regulation of GnRH receptors by progesterone and inhibin in ovine pituitary cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Laws, S.C.

    1988-01-01

    The effects of progesterone (P{sub 4}) and the gonadal protein, inhibin, on gonadotropin-releasing hormone (GnRH) receptor number and binding affinity were investigated in vitro, using ovine pituitary cells in culture. Changes in GnRH binding were correlated with GnRH-stimulated luteinizing hormone (LH) release following pretreatment with P{sub 4} and inhibin. Ovine pituitary cells in culture were preincubated with P{sub 4} or porcine inhibin (I{sub P}) for 24 or 48 hours (h). Cells were collected and analyzed for GnRH binding using a radioligand-receptor assay. des-Gly{sup 10}-(D-Ala{sup 6})-LHRH-ethyl-amide was used as the radiolabeled GnRh superagonist analog (mono-{sup 125}I-GnRH-A) and as competing ligand. Treatment with P{sub 4} progressively decreased GnRH-A binding capacity by 44.3% and 71.8% of the control following pretreatment for 24 or 48 h, respectively. When P{sub 4} was removed from the cultures, GnRH-A binding capacity partially returned to control levels within 24 h. Decreased GnRH-A binding was closely correlated with the reduction in GnRH-stimulated LH release which was observed following 24 or 48 h pretreatment with P{sub 4}.

  10. SUNCT syndrome associated with pituitary tumor: case report Síndrome SUNCT associada a tumor de hipófise: relato de caso

    Directory of Open Access Journals (Sweden)

    Pedro A.S. Rocha Filho

    2006-06-01

    Full Text Available For twelve years, the subject of this report, a 38-year-old man, presented a clinical condition compatible with the SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. He presented a stabbing and intense daily pain located in the left pre-auricular and temporal regions. Each of these intense pain attacks lasted around one minute and presented a frequency of two to eight times per day. The pain was associated with ipsilateral lacrimation, conjunctival injection and rhinorrhea. MRI revealed a pituitary tumor with little suprasellar extent. The subject’s serial assays of prolactin, GH, TSH and ACTH were within normal levels. Following transsphenoidal hypophysectomy, with complete removal of the tumor, the subject no more presented pain. The pathological diagnosis was non-secreting adenoma. Fourteen months after the surgery, he remains symptom-free.O paciente relatado neste artigo apresentou uma condição clínica compatível com síndrome SUNCT (cefaléia de curta duração, unilateral, neuralgiforme com hiperemia conjuntival e lacrimejamento. Ele referia dor diária, intensa, em facada, localizada na região pré-auricular e temporal esquerdas. Cada ataque de dor permanecia por cerca de um minuto, com freqüência de duas a oito vezes por dia. A dor se acompanhava de lacrimejamento ipsolateral, congestão conjuntival e rinorréia. A RM mostrou um tumor de hipófise com pouca extensão suprasselar. Dosagens de prolactina, GH, TSH e ACTH estavam em níveis normais. Foi então submetido a hipofisectomia transesfenoidal com remoção completa do tumor após o que a dor cessou completamente. O diagnóstico anátomo-patológico foi adenoma não secretor. Quatorze meses após a cirurgia, o paciente permanecia livre de dor.

  11. The pathology of pituitary adenomas from a clinical perspective.

    Science.gov (United States)

    Dworakowska, Dorota; Korbonits, Marta; Aylwin, Simon; McGregor, Alan; Grossman, Ashley B

    2011-01-01

    Pituitary adenomas present with a variety of clinical endocrine manifestations and arise in a sporadic setting or rarely as part of hereditary genetic syndromes. Molecular analysis of familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of identified genes involved in pituitary tumorigenesis is progressively increasing. The possible resulting mechanisms of action involve abnormalities in signal transduction pathways, cell cycle regulators, growth factors, chromosome stability and others. Further studies are needed to evaluate the clinical significance of genetic alterations and their implications for patient prognosis, as well as to identify targets for existing and new therapeutic options. The aim of this review is to focus on the molecular pathology of pituitary adenomas from a practical perspective and discuss the possible clinical implications which may relate to particular molecular alterations. We have summarised familial syndromes related to pituitary adenomas and considered the prognostic value of selected molecular alterations in these tumors.

  12. Ikaros and its interacting partner CtBP target the metalloprotease ADAMTS10 to modulate pituitary cell function.

    Science.gov (United States)

    Shen, Zhongyi; Asa, Sylvia L; Ezzat, Shereen

    2017-01-05

    We have previously described the expression and up-regulation of the C-terminal Binding Protein (CtBP) in response to pituitary hypoxia. This co-repressor interacts with the hematopoietic factor Ikaros to target several components implicated in cellular growth and apoptotic pathways. To identify common transcriptional pituitary targets we performed promoter arrays using Ikaros and CtBP chromatin immunoprecipitated (ChIP) DNA from pituitary AtT20 cells. This approach yielded a finite list of gene targets common to both transcription factors. Of these, the metalloprotease ADAMTS10 emerged as a validated target. We show the ability of Ikaros to bind the ADAMTS10 promoter, influence its transfected activity, and induce endogenous gene expression. ADAMTS10 is expressed in primary pituitary cells and is down-regulated in Ikaros null mice. Further, knockdown of ADAMTS10 in AtT20 cells recapitulates the impact of Ikaros deficiency on POMC/ACTH hormone expression. These results uncover a novel role for the metalloprotease ADAMTS10 in the pituitary. Additionally, they position this metalloprotease as a potential functional integrator of the Ikaros-CtBP chromatin remodeling network.

  13. Functional differentiation of the anterior pituitary cells in the fetal pig. An ultrastructural immunocytochemical study.

    Science.gov (United States)

    Dacheux, F

    1984-01-01

    The fetal porcine pituitary was investigated by means of ultrastructural immunocytochemistry (1) to identify the first cells synthesizing the adenohypophyseal hormones, (2) to follow their differentiation during fetal development, and (3) to compare their ultrastructural characteristics with those of mature adult cells. The first ACTH-cells, which produced and stored ACTH, beta-LPH, beta-MSH, and alpha- and beta-endorphin in the same granules, were very numerous at day 34 and displayed a uniform morphology. At day 50 and thereafter, until the end of gestation, the ACTH-cells differed in their appearance probably reflecting various stages of differentiation of one cell type. The GH-cells gained rapidly ultrastructural features comparable to those of mature GH-cells. In contrast, in the case of PRL-cells, which appeared only at the end of the gestation period as immature elements containing very small secretory granules, the morphological maturation seemed to take place only after birth. The first cells synthesizing the glycoprotein hormones (LH alpha, LH beta, FSH and TSH) displayed ultrastructural features of immature cells. At day 50, their ultrastructural organization started to show a different pattern. At the end of gestation, the TSH-cells and the gonadotropic cells displayed the ultrastructural features of mature cells.

  14. Selective use of peri-operative steroids in pituitary tumor surgery: escape from dogma

    Directory of Open Access Journals (Sweden)

    Jacqueline Marie Regan

    2013-03-01

    Full Text Available Objective: Traditional neurosurgical practice calls for administration of peri-operative stress-dose steroids for sellar-suprasellar masses undergoing operative treatment. This practice is considered critical to prevent peri-operative complications associated with hypoadrenalism, such as hypotension and circulatory collapse. However, stress-dose steroids complicate the management of these patients. It has been our routine practice to use stress steroids during surgery only if the patient has clinical or biochemical evidence of hypocortisolism pre-operatively. We wanted to be certain that this practice was safe.Methods: We present our retrospective analysis from a consecutive series of 114 operations in 109 patients with sellar and/or suprasellar tumors, the majority of whom were managed without empirical stress-dose steroid coverage. Only patients who were hypoadrenal pre-operatively or who had suffered apoplexy were given stress dose coverage during surgery. We screened for biochemical evidence of hypoadrenalism as a result of surgery by measuring immediate post-operative AM serum cortisol levels.Results: There were no adverse events related to the selective use of cortisol replacement in this patient population. Conclusions: Our experience demonstrates that selective use of corticosteroid replacement is safe; it simplifies the management of the patients, and has advantages over empiric dogmatic steroid coverage.

  15. A SELF-PRIMING EFFECT OF LHRH ON LH SECRETION IN DISPERSED ANTERIOR PITUITARY CELLS OF ADULT MALE RAT

    Institute of Scientific and Technical Information of China (English)

    QUZhi-Chao; GUOJing; GUOJian

    1989-01-01

    LHRH self-priming effect is simply defmed as an enhancement of LH response to LHRH, i. e., a second challenge with LHRH elicits more LH secretion as compared to the first challenge. The present study is to observe whether this phenomenon exists in perfused anterior pituitary (AP) cells of adult male rat. Dispersed AP cells of adult SD

  16. DIAGNOSIS AND TREATMENT OF THE PITUITARY METASTASES

    Institute of Scientific and Technical Information of China (English)

    连伟; 任祖渊; 苏长保

    2004-01-01

    Thee cases of pituitary metastases were reported. They all had operations and the pathological examination confirming the diagnosis. The clinical features of diabetes insipidus and extraocular nerve palsy were presented. In two cases, the original tumors were bronchioloalveolar carcinoma; in the other one, the original tumor was unknown. All three cases had poor outcome. These cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary benign tumor, such as pituitary adenoma. Especially in the presence of suggestive symptoms such as diabetes insipidus and/or cranical nerve paralysis, the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.

  17. Robo-Enabled Tumor Cell Extrusion.

    Science.gov (United States)

    Richardson, Helena E; Portela, Marta

    2016-12-19

    How aberrant cells are removed from a tissue to prevent tumor formation is a key question in cancer biology. Reporting in this issue of Developmental Cell, Vaughen and Igaki (2016) show that a pathway with an important role in neural guidance also directs extrusion of tumor cells from epithelial tissues.

  18. Evolution of cooperation among tumor cells.

    Science.gov (United States)

    Axelrod, Robert; Axelrod, David E; Pienta, Kenneth J

    2006-09-01

    The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

  19. Effect of tumor cells and tumor microenvironment on NK-cell function.

    Science.gov (United States)

    Vitale, Massimo; Cantoni, Claudia; Pietra, Gabriella; Mingari, Maria Cristina; Moretta, Lorenzo

    2014-06-01

    The ability of tumors to manage an immune-mediated attack has been recently included in the "next generation" of cancer hallmarks. In solid tumors, the microenvironment that is generated during the first steps of tumor development has a pivotal role in immune regulation. An intricate net of cross-interactions occurring between tumor components, stromal cells, and resident or recruited immune cells skews the possible acute inflammatory response toward an aberrant ineffective chronic inflammatory status that favors the evasion from the host's defenses. Natural killer (NK) cells have powerful cytotoxic activity, but their activity may be eluded by the tumor microenvironment. Immunosubversion, immunoediting or immunoselection of poorly immunogenic tumor cells and interference with tumor infiltration play a major role in evading NK-cell responses to tumors. Tumor cells, tumor-associated fibroblasts and tumor-induced aberrant immune cells (i.e. tolerogenic or suppressive macrophages, dendritic cells (DCs) and T cells) can interfere with NK-cell activation pathways or the complex receptor array that regulate NK-cell activation and antitumor activity. Thus, the definition of tumor microenvironment-related immunosuppressive factors, along with the identification of new classes of tissue-residing NK-like innate lymphoid cells, represent key issues to design effective NK-cell-based therapies of solid tumors.

  20. Simultaneous measurement of hormone release and secretagogue binding by individual pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P.F.; Neill, J.D.

    1987-08-01

    The quantitative relationship between receptor binding and hormone secretion at the single-cell level was investigated in the present study by combining a reverse hemolytic plaque assay for measurement of luteinizing hormone (LH) secretion from individual pituitary cells with an autoradiographic assay of /sup 125/I-labeled gonadontropin-releasing hormone (GnRH) agonist binding to the same cells. In the plaque assay, LH secretion induces complement-mediated lysis of the LH-antibody-coated erythrocytes around the gonadotropes, resulting in areas of lysis (plaques). LH release from individual gonadotropes was quantified by comparing radioimmunoassayable LH release to hemolytic area in similarly treated cohort groups of cells; plaque area was linearly related to the amount of LH secreted. Receptor autoradiography was performed using /sup 125/I-labeled GnRH-A (a superagonist analog of GnRH) both as the ligand and as the stimulant for LH release in the plaque assay. The grains appeared to represent specific and high-affinity receptors for GnRH because (i) no pituitary cells other than gonadotropes bound the labeled ligand and (ii) grain development was progressively inhibited by coincubation with increasing doses of unlabeled GnRH-A. The authors conclude that GnRH receptor number for any individual gonadotrope is a weak determinant of the amount of LH it can secrete; nevertheless, full occupancy of all its GnRH receptors is required for any gonadotrope to reach its full LH-secretory capacity. Apparently the levels of other factors comprising the steps along the secretory pathway determine the secretory capacity of an individual cell.

  1. Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats.

    Science.gov (United States)

    Magri, María Laura; Gottardo, María Florencia; Zárate, Sandra; Eijo, Guadalupe; Ferraris, Jimena; Jaita, Gabriela; Ayala, Mariela Moreno; Candolfi, Marianela; Pisera, Daniel; Seilicovich, Adriana

    2016-03-01

    Hormones locally synthesized in the anterior pituitary gland are involved in regulation of pituitary cell renewal. In the pituitary, testosterone (T) may exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17β-estradiol (E2) by 5α-reductase and aromatase activity, which are expressed in this gland. Previous reports from our laboratory showed that estrogens modulate apoptosis of lactotropes and somatotropes from female rats. Now, we examined the in vitro and in vivo effects of gonadal steroids on apoptosis of anterior pituitary cells from adult male rats. T in vitro did not modify apoptosis in anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non-aromatizable androgen, exerted direct antiapoptotic action on total anterior pituitary cells and folliculo-stellate cells, but not on lactotropes, somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic effect on total cells as well as on lactotropes and somatotropes. Incubation of anterior pituitary cells with T in presence of Finasteride, an inhibitor of 5α-reductase, increased the percentage of TUNEL-positive cells. In vivo administration of DHT to GNX rats reduced apoptosis in the anterior pituitary whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the cell cycle. In summary, our results indicate that DHT and E2 have opposite effects on apoptosis in the anterior pituitary gland suggesting that local metabolization of T to these steroids could be involved in pituitary cell turnover in males. Changes in expression and/or activity of 5α-reductase and aromatase may play a role in the development of anterior pituitary tumors.

  2. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    Science.gov (United States)

    2016-08-25

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  3. Isolation of dendritic-cell-like S100β-positive cells in rat anterior pituitary gland.

    Science.gov (United States)

    Horiguchi, Kotaro; Fujiwara, Ken; Yoshida, Saishu; Higuchi, Masashi; Tsukada, Takehiro; Kanno, Naoko; Yashiro, Takashi; Tateno, Kozue; Osako, Shunji; Kato, Takako; Kato, Yukio

    2014-07-01

    S100β-protein-positive cells in the anterior pituitary gland appear to possess multifunctional properties. Because of their pleiotropic features, S100β-positive cells are assumed to be of a heterogeneous or even a non-pituitary origin. The observation of various markers has allowed these cells to be classified into populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. The isolation and characterization of each heterogeneous population is a prerequisite for clarifying the functional character and origin of the cells. We attempt to isolate two of the subpopulations of S100β-positive cells from the anterior lobe. First, from transgenic rats that express green fluorescent protein (GFP) driven by the S100β protein promoter, we fractionate GFP-positive cells with a cell sorter and culture them so that they can interact with laminin, a component of the extracellular matrix. We observe that one morphological type of GFP-positive cells possesses extended cytoplasmic processes and shows high adhesiveness to laminin (process type), whereas the other is round in shape and exhibits low adherence to laminin (round type). We successfully isolate cells of the round type from the cultured GFP-positive cells by taking advantage of their low affinity to laminin and then measure mRNA levels of the two cell types by real-time polymerase chain reaction. The resultant data show that the process type expresses vimentin (mesenchymal cell marker) and glial fibrillary acidic protein (astrocyte marker). The round type expresses dendritic cell markers, CD11b and interleukin-6. Thus, we found a method for isolating dendritic-cell-like S100β-positive cells by means of their property of adhering to laminin.

  4. Cancer Stem Cells and Pediatric Solid Tumors

    Directory of Open Access Journals (Sweden)

    Gregory K. Friedman

    2011-01-01

    Full Text Available Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC, has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

  5. Pituitary infiltration by non-Hodgkin's lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Aral Ferihan

    2009-11-01

    Full Text Available Abstract Introduction Pituitary adenomas represent the most frequently observed type of sellar masses; however, the presence of a rapidly growing sellar tumor, diabetes insipidus, ophthalmoplegia and headaches in an older patient strongly suggests metastasis to the pituitary. Since the anterior pituitary has a great reserve capacity, metastasis to the pituitary and pituitary involvement in lymphoma are usually asymptomatic. Whereas diabetes insipidus is the most frequent symptom, patients can present with headaches, ophthalmoplegia and bilateral hemianopsia. Case presentation A 70-year-old woman with no previous history of malignancy presented with headaches, right oculomotor nerve palsy and diabetes insipidus. As magnetic resonance imaging revealed a sellar mass involving the pituitary gland and infundibular stalk, which also extended into the right cavernous sinus and sphenoid sinus, the patient underwent an immediate transsphenoidal decompression surgery. Her prolactin was 102.4 ng/ml, whereas her gonadotropic hormone levels were low. A low level of urine osmolality after overnight water deprivation, along with normal plasma osmolality suggested diabetes insipidus. Histological examination revealed that the mass had been the infiltration of a high grade B-cell non-Hodgkin's lymphoma involving respiratory system epithelial cells. Paranasal sinus computed tomography scanning and magnetic resonance imaging of the thorax and abdomen were performed. Since magnetic resonance imaging did not reveal any abnormality, after paranasal sinus computed tomography was performed, we concluded that the primary lymphoma originated from the sphenoid sinus and infiltrated the pituitary. Chemotherapy and radiotherapy to the sellar area were planned, but the patient died and her family did not permit an autopsy. Conclusion Lymphoma infiltration to the pituitary is difficult to differentiate from pituitary adenoma, meningioma and other sellar lesions. To plan the

  6. Cloning of Porcine Pituitary Tumor Transforming Gene 1 and Its Expression in Porcine Oocytes and Embryos

    Science.gov (United States)

    Liu, Shuai; Nong, Suqun; Ma, Qingyan; Chen, Baojian; Liu, Mingjun; Pan, Tianbiao; Liao, D. Joshua

    2016-01-01

    The maternal-to-embryonic transition (MET) is a complex process that occurs during early mammalian embryogenesis and is characterized by activation of the zygotic genome, initiation of embryonic transcription, and replacement of maternal mRNA with embryonic mRNA. The objective of this study was to reveal the temporal expression and localization patterns of PTTG1 during early porcine embryonic development and to establish a relationship between PTTG1 and the MET. To achieve this goal, reverse transcription-polymerase chain reaction (RT-PCR) was performed to clone porcine PTTG1. Subsequently, germinal vesicle (GV)- and metaphase II (MII)-stage oocytes, zygotes, 2-, 4-, and 8-cell-stage embryos, morulas, and blastocysts were produced in vitro and their gene expression was analyzed. The results revealed that the coding sequence of porcine PTTG1 is 609-bp in length and that it encodes a 202-aa polypeptide. Using qRT-PCR, PTTG1 mRNA expression was observed to be maintained at high levels in GV- and MII-stage oocytes. The transcript levels in oocytes were also significantly higher than those in embryos from the zygote to blastocyst stages. Immunohistochemical analyses revealed that porcine PTTG1 was primarily localized to the cytoplasm and partially localized to the nucleus. Furthermore, the PTTG1 protein levels in MII-stage oocytes and zygotes were significantly higher than those in embryos from the 2-cell to blastocyst stage. After fertilization, the level of this protein began to decrease gradually until the blastocyst stage. The results of our study suggest that porcine PTTG1 is a new candidate maternal effect gene (MEG) that may participate in the processes of oocyte maturation and zygotic genome activation during porcine embryogenesis. PMID:27058238

  7. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus

    Science.gov (United States)

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I131 therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH. PMID:27656301

  8. Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs

    OpenAIRE

    Matsumoto, Itsuro; Inoue, Yasuhisa; Shimada, Toshio; Aikawa, Tadaomi

    2001-01-01

    Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebro...

  9. Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone.

    OpenAIRE

    Hellerman, J G; Cone, R C; Potts, J. T.; Rich, A; Mulligan, R C; Kronenberg, H M

    1984-01-01

    In order to study the functions of precursors to secreted proteins, we expressed cloned DNA encoding human preproparathyroid hormone (preproPTH) in rat pituitary cells. We first constructed a recombinant plasmid containing human preproPTH cDNA and retroviral control signals. This recombinant plasmid was transfected into psi-2 cells, a packaging cell line that produces Moloney murine leukemia viral particles containing no retroviral RNA. The transfected psi-2 cells generated helper-free recomb...

  10. Metastasis and circulating tumor cells

    NARCIS (Netherlands)

    Dalum, van G.; Holland, L.; Terstappen, L.W.M.M.

    2012-01-01

    Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulati

  11. 垂体瘤切除术后低钠血症32例分析%Clinical Analysis of Postoperative Hyponatremia of Pituitary Tumor In 32 patients

    Institute of Scientific and Technical Information of China (English)

    高建洲; 常祥平; 陈亢实; 潘乐坤; 孔昕

    2009-01-01

    Objective To explore clinical treatment of postoperative hyponatremia of pituitary tumor. Meth-ods 32 cases of patients with postoperative hyponatremia of pituitary tumor were randomly divided into control group and treatment group. The control group(n = 15) was treated with routine western medicine, and the treatment group(n = 17) was treated with water limited and sodium supplemented based on the control group. The clinical effect was observed between control group and treatment group. Results The clinical effect in the treatment group was signifi-cantly higher than that of the control group(P <0.05). Conclusion The treatment of water limited and sodium sup-plemented on postoperative hyponatremia of pituitary tumor is better.%目的 探讨垂体瘤切除术后低钠血症的临床处理方法 .方法 32例垂体瘤切除术后低钠血症患者,随机分为对照组(n=15)和治疗组(n=17),其中对照组予以西医常规处理,治疗组在对照组基础上限水补钠,比较两组患者的临床疗效.结果 治疗组临床疗效明显高于对照组(P<0.05).结论 应用限水补钠对垂体瘤切除术后低钠血症的治疗效果好.

  12. SYNOVIAL GIANT CELL TUMOR OF THE KNEE.

    Science.gov (United States)

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2009-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  13. Intrasellar pituitary mucocele: diagnostic dilemma.

    Science.gov (United States)

    Tang, Ing Ping; Chai, Chun Kian; Kumar, Gnana; Prepageran, Narayanan; Waran, Vicknes

    2014-06-01

    Isolated intrasellar pituitary mucocele following transsphenoidal sinus surgery is extremely rare. The clinical features resemble a pituitary tumor, therefore careful radiological interpretation is crucial to reach the correct diagnosis. We report a case of intrasellar mucocele who had transsphenoidal sinus surgery performed 15 years prior.

  14. Heterogeneity of secretory granules of silent pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R

    1988-01-01

    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...... approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas....

  15. [Granular cell tumor of the larynx].

    Science.gov (United States)

    Modrzyński, M; Wróbel, B; Zawisza, E; Drozd, K

    1999-09-01

    Granular cell tumor is an unusual growth of probably neuroectodermal histogenesis, first reported by Abrikossoff in 1926 with the name of myoblastenmyoma. Authors described a case of a 54 year man with laryngeal seat of granular-cell myoblastoma. In this case Abrikossoff tumor was located in the right vocal chord. The tumor was treated successfully surgically by microlaryngoscopy. The etiology, clinical features and diagnostic difficulties are discussed.

  16. Generation of immortal cell lines from the adult pituitary: role of cAMP on differentiation of SOX2-expressing progenitor cells to mature gonadotropes.

    Directory of Open Access Journals (Sweden)

    Ginah L Kim

    Full Text Available The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages.

  17. Granular cell tumors of the tracheobronchial tree.

    NARCIS (Netherlands)

    Maten, van der J; Blaauwgeers, JL; Sutedja, G.; Kwa, HB; Postmus, P.E.; Wagenaar, SS

    2003-01-01

    OBJECTIVE: To describe the population-based incidence and clinical characteristics of granular cell tumors of the tracheobronchial tree. METHODS: All newly registered tracheobronchial granular cell tumors in the Dutch Network and National Database for Pathology for 10 consecutive years (1990-1999) w

  18. Treatment Option Overview (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  19. General Information about Ovarian Germ Cell Tumors

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  20. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  1. Tumor Evasion from T Cell Surveillance

    Directory of Open Access Journals (Sweden)

    Katrin Töpfer

    2011-01-01

    Full Text Available An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.

  2. The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling

    NARCIS (Netherlands)

    Budry, L.; Balsalobre, A.; Gauthier, Y.; Khetchoumian, K.; L'Honore, A.; Vallette-Kasic, S.; Brue, T; Figarella-Branger, D.; Meij, B.P.; Drouin, J.

    2012-01-01

    Genes Dev. 2012 Oct 15;26(20):2299-310. doi: 10.1101/gad.200436.112. The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling. Budry L, Balsalobre A, Gauthier Y, Khetchoumian K, L'honoré A, Vallette S, Brue T, Figarella-Branger D, Meij B, Drou

  3. Genetics Home Reference: familial isolated pituitary adenoma

    Science.gov (United States)

    ... named? Additional Information & Resources MedlinePlus (6 links) Encyclopedia: Acromegaly Encyclopedia: Gigantism Encyclopedia: Pituitary Tumor Encyclopedia: Prolactinoma Health Topic: Endocrine ...

  4. Pituitary Tumors Fact Sheet

    Science.gov (United States)

    ... include fatigue, dizziness, dry skin, irregular periods in women, and sexual dysfunction in men. Other symptoms depend on the hormone ... can cause irregular or absent menstrual periods in women. They can also cause a ... dysfunction and breast enlargement. These conditions can have serious ...

  5. Stages of Pituitary Tumors

    Science.gov (United States)

    ... reflexes work. This may also be called a neuro exam or a neurologic exam. MRI (magnetic resonance ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

  6. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  7. Pituitary stalk lesion in a 13-year-old female.

    Science.gov (United States)

    Zilbermint, Mihail; Ramnitz, Mary S; Lodish, Maya B; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J; Quezado, Martha M; Stratakis, Constantine A

    2014-03-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.

  8. Pituitary stalk lesion in a 13-year-old female

    Science.gov (United States)

    Zilbermint, Mihail; Ramnitz, Mary S.; Lodish, Maya B.; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J.; Quezado, Martha M.

    2016-01-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI. PMID:24129100

  9. Tumor's other immune targets: dendritic cells.

    Science.gov (United States)

    Esche, C; Lokshin, A; Shurin, G V; Gastman, B R; Rabinowich, H; Watkins, S C; Lotze, M T; Shurin, M R

    1999-08-01

    The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co-culture of murine or human DC with different tumor cell lines for 4-48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time- and dose-dependent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apoptosis involved regulation of Bcl-2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC-based immunotherapies for cancer and other immune diseases.

  10. Inhibitory effect of resveratrol on the proliferation of GH3 pituitary-adenoma cells and voltage-dependent potassium current

    Institute of Scientific and Technical Information of China (English)

    Ming Chu; Lanlan Wei; Chao Wang; Yu Cheng; Kongbin Yang; Baofeng Yang

    2006-01-01

    BACKGROUND:Recent researches indicate that activation of potassium channel is likely to cause many kinds of cells to proliferate and differentiate;using chemical to block the potassium channel can restrain the proliferation of small lung-cancer cells.breast cancer.prostate cancer and human lymphocyte,etc.Previous researches proved that resveratrol(RE),a selective estrogen receptor modulator(SERM).could inhibit growth of GH3 calls,induce apoptosis,and resist tumor through interfering K+ channel.OBJECTIVE:To investigate the effects of RE on Voltage-dependent K+ current [Ik(v)] and cell proliferation in GH3 pituitary-tumor cells.DESIGN:Observational contrast study.SETTING:Department of Neurosurgery.the First Clinical Hospital of Harbin Medical University;Department of Microbiology,Harbin Medical University;Department of Pharmacology,Harbin Medical University.MATERIALS: GH3 pituitary-tumor cell line of rats was purchased from the American Type Culture Collection (ATCC).RE and[3-(4,5-dimethylthiazo1-2-y1)-2.5-diphenyl-tetrazolium bromide](MTT)were obtained from Sigma Chemical CO,St Louis,USA;Ham's F-10 medium from Gibco BRL;Equine serum and fetal bovine serum from Hyclone Laboratories,Logan,UT;FACSCalibur flow cytometer from BD Company,USA.RE was dissolved in ethanol and stored at-20 ℃.It was diluted to different concentrations (10.50,100 μmol/L)with medium and extra cellular solution when needed.rhe final concentration of ethanol was Jess than 0.01%.METHODS:The experiment was carried out in the Department of Microbiology and Pharmacology of Harbin Medical University from March 2005 to January 2006.①Cell preparation:Proliferating indexes affected by 10.50 and 100 μmol/L RE were measured with MTT,respectively.0.0001 volume fraction of ethan ol was added into control group.Inhibitory rate of cellular growth was calculated as the following formula:Inhibitory rate (%)=(1-A value in experimental group/A value in control group)x100%.The experiments mentioned above were

  11. [Involution of gonadotrophic cells of the pituitary gland in the male frog, Rana esculenta, after section of the pituitary stem].

    Science.gov (United States)

    Legait, H; Helas, G

    1976-01-01

    One and two months after section of the hypophyseal stalk in the male frog. Rana esculenta, and involution of numerous gonadotrophic cells, contrasting with the normal aspect of the eosinophilic cells can be observed.

  12. Influência dos níveis de prolactina e tamanho tumoral na função hipofisária pós-operatória em macroadenomas hipofisários clinicamente não-funcionantes Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfuncioning pituitary macroadenomas

    Directory of Open Access Journals (Sweden)

    Ana Luiza Vidal Fonseca

    2002-09-01

    Full Text Available OBJETIVO: Estudar a influência da hiperprolactinemia e de tamanho tumoral na função hipofisária em macroadenomas hipofisários clinicamente não funcionantes. MÉTODOS: Foram analisados 23 pacientes com macroadenomas hipofisários clinicamente não funcionantes, com exames de imagem (tomografia computadorizada ou ressonância magnética e dosagens hormonais basais; 16 tinham provas de função hipotálamo-hipofisária (megateste pré-operatórios. Todos os tumores tiveram diagnóstico histológico e em 17 foi realizado também estudo imuno-histoquímico para os hormônios adeno-hipofisários. A análise estatística foi feita por meio dos testes t de Student, qui-quadrado, exato de Fisher e de Mc Neman. O nível de significância adotado foi 5% (pOBJECTIVE: To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfuncioning pituitary macroadenomas. METHODS: Twenty three patients with clinically nonfuncioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests. All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis . The level of significance adopted was 5% (p<0.05. RESULTS: Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm ± 1.04. In the preoperative, 5 (21.7% patients did not show laboratorial hormonal deficit, 9 (39.1% developed hyperprolactinemia, 13 (56,5% normal levels of prolactin (PRL and 1 (4.3% subnormal; 18 (78.3% patients developed hypopituitarism (4 pan-hypopituitarism. Nineteen patients (82.6% underwent transsfenoidal approach, 3 (13% craniotomy and 1 (4.4% combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical

  13. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2009-09-01

    Full Text Available Abstract Background Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH3/B6/F10, originally subcloned from GH3 cells based on its ability to express high levels of the membrane estrogen receptor-α. Methods We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Results Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH3/B6/F10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Conclusion Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell

  14. Enhanced nestin expression and small blood vessels in human pituitary adenomas.

    Science.gov (United States)

    Perez-Millan, María Inés; Berner, Silvia Inés; Luque, Guillermina María; De Bonis, Cristian; Sevlever, Gustavo; Becu-Villalobos, Damasia; Cristina, Carolina

    2013-09-01

    The role of angiogenesis in human pituitary tumor progression is questioned. Our aim was to characterize the morphologic changes that occur in the vasculature of pituitary adenomas, in correlation with the expression of nestin, a protein found in endothelial cells of newly formed vessels of developing organs. We also evaluated the relation of angiogenic markers and nestin with Ki-67 index. Immunohistochemical studies were performed on paraffin embedded samples of 47 pituitary adenomas and six normal pituitaries. We determined microvessel density (number of CD31+ or CD34+ vessels per square millimetre), vascular area (cumulative area occupied by vessels), average vessel size, and further classified vessels as small ( 100 μm2). We correlated the above parameters with nestin expression and Ki-67 index. Lower vascular area compared to normal tissue was found in adenomas (p vessels than control pituitaries (p controls, so that nestin positive area was significantly higher in tumors. Furthermore, nestin area correlated positively with the % of small vessels. Ki-67 correlated neither with vascular area nor with nestin expression. In human pituitary tumors there was a predominance of small capillaries in correlation with increased expression of the progenitor marker nestin. We suggest that angiogenesis is an active process in these tumors, in spite of their low total vascular area when compared to normal pituitaries.

  15. CellTracks cytometer for detection of circulating tumor cells

    NARCIS (Netherlands)

    Tibbe, A.G.J.; Kooi, van der A.; Groot, de M.R.; Vermes, I.

    2003-01-01

    Introduction: In patients with carcinomas, tumor cells are shed into the circulation. The number of the circulating tumor cells is low and technology is needed that has sufficient sensitivity and specificity to enumerate and characterize these cells. The CellTracks system was developed to provide an

  16. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  17. Giant cell tumor in adipose package Hoffa

    Science.gov (United States)

    Etcheto, H. Rivarola; Escobar, G.; Blanchod, C. Collazo; Palanconi, M.; Zordan, J.; Salinas, E. Alvarez; Autorino₁, Carlos

    2017-01-01

    Tumors of adipose Hoffa package are very uncommon, with isolated cases reported in the literature. His presentation in pediatric patients knee is exceptional. The most frequently described tumors are benign including vellonodular synovitis. The extra-articular localized variant there of is known as giant cell tumor of the tendon sheath. It is characterized by locally aggressive nature, and has been described in reports of isolated cases. Objective: A case of giant cell tumor of the tendon sheath in adipose presentation package Hoffa in pediatric patients is presented in this paper. Methods: male patient eleven years with right knee pain after sports practice was evaluated. Physical examination, showed limited extension -30º, joint effusion, stable negative Lachman maneuver without peripheral knee laxity. MRI hyperintense on tumor is observed in T2 and hypointense on T1 homogeneous and defined edges content displayed prior to LCA related to adipose Hoffa package. Results: The tumor specimen was obtained and histopathology is defined as densely cellular tissue accumulation of xantomisados fibrocollagenous with histiocytes and multinucleated giant cells, compatible with giant cell tumor of tendon sheath. Conclusion: The presentation of giant cell tumors of the tendon sheath in Hoffa fat pad is exceptional. However, his suspicion allows adequate preoperative surgical planning, as a whole resection is the only procedure that has been shown to decrease the rate of recurrence of this disease.

  18. HIF-1α Inhibition Sensitized Pituitary Adenoma Cells to Temozolomide by Regulating Presenilin 1 Expression and Autophagy.

    Science.gov (United States)

    Kun, Zhang; Yuling, Yang; Dongchun, Wang; Bingbing, Xie; Xiaoli, Li; Bin, Xu

    2016-12-01

    Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1α has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1α could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1α knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1α knockdown could inhibit temozolomide-induced autophagy in rat pituitary adenoma GH3 cells and thus increase antitumor efficacy of temozolomide. Furthermore, we found hypoxia-inducible factor 1α knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1α could regulate lysosomal pH value through regulating full length presenilin 1 expression, and exogenous reexpression of presenilin 1could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1α knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.

  19. Multimodal Navigation in Endoscopic Transsphenoidal Resection of Pituitary Tumors Using Image-Based Vascular and Cranial Nerve Segmentation: A Prospective Validation Study.

    Science.gov (United States)

    Dolati, Parviz; Eichberg, Daniel; Golby, Alexandra; Zamani, Amir; Laws, Edward

    2016-11-01

    Transsphenoidal surgery (TSS) is the most common approach for the treatment of pituitary tumors. However, misdirection, vascular damage, intraoperative cerebrospinal fluid leakage, and optic nerve injuries are all well-known complications, and the risk of adverse events is more likely in less-experienced hands. This prospective study was conducted to validate the accuracy of image-based segmentation coupled with neuronavigation in localizing neurovascular structures during TSS. Twenty-five patients with a pituitary tumor underwent preoperative 3-T magnetic resonance imaging (MRI), and MRI images loaded into the navigation platform were used for segmentation and preoperative planning. After patient registration and subsequent surgical exposure, each segmented neural or vascular element was validated by manual placement of the navigation probe or Doppler probe on or as close as possible to the target. Preoperative segmentation of the internal carotid artery and cavernous sinus matched with the intraoperative endoscopic and micro-Doppler findings in all cases. Excellent correspondence between image-based segmentation and the endoscopic view was also evident at the surface of the tumor and at the tumor-normal gland interfaces. Image guidance assisted the surgeons in localizing the optic nerve and chiasm in 64% of cases. The mean accuracy of the measurements was 1.20 ± 0.21 mm. Image-based preoperative vascular and neural element segmentation, especially with 3-dimensional reconstruction, is highly informative preoperatively and potentially could assist less-experienced neurosurgeons in preventing vascular and neural injury during TSS. In addition, the accuracy found in this study is comparable to previously reported neuronavigation measurements. This preliminary study is encouraging for future prospective intraoperative validation with larger numbers of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Herceptin conjugates linked by EDC boost direct tumor cell death via programmed tumor cell necrosis.

    Directory of Open Access Journals (Sweden)

    Jiemiao Hu

    Full Text Available Tumor-targeted antibody therapy is one of the safest biological therapeutics for cancer patients, but it is often ineffective at inducing direct tumor cell death and is ineffective against resistant tumor cells. Currently, the antitumor efficacy of antibody therapy is primarily achieved by inducing indirect tumor cell death, such as antibody-dependent cell cytotoxicity. Our study reveals that Herceptin conjugates, if generated via the crosslinker EDC (1-ethyl-3-(3-dimethylaminopropyl carbodiimide hydrochloride, are capable of engendering human epidermal growth factor receptor 2 (Her2 positive tumor cells death. Using a high-performance liquid chromatography (HPLC system, three peaks with estimated molecular weights of antibody monomer, dimer, and trimer were isolated. Both Herceptin trimer and dimer separated by HPLC induced significant levels of necrotic tumor cell death, although the trimer was more effective than the dimer. Notably, the Herceptin trimer also induced Herceptin-resistant tumor cell death. Surprisingly different from the known cell death mechanism that often results from antibody treatment, the Herceptin trimer elicited effective and direct tumor cell death via a novel mechanism: programmed cell necrosis. In Her2-positive cells, inhibition of necrosis pathways significantly reversed Herceptin trimer-induced cell death. In summary, the Herceptin trimer reported herein harbors great potential for overcoming tumor cell resistance to Herceptin treatment.

  1. Suprasellar/pineal bifocal germ cell tumors.

    Science.gov (United States)

    Cuccia, Vicente; Alderete, Daniel

    2010-08-01

    Intracranial germ cell tumors (GCT) arise from embryonal rests of germinal cells. The aim of this report is to analyze a small group of GCT located simultaneously in the suprasellar and pineal regions without seeding either between both tumors or to other places. We named this group as suprasellar/pineal bifocal germ cell tumors (SPBT). A retrospective review of a series of 25 GCT showed a) 16 cases of unifocal non-disseminated pineal or sellar GCT, b) one case of unifocal disseminated pineal GCT, c) three cases with suprasellar and pineal double tumors with dissemination, and d) five cases with SPBT. The analysis is focused on the latter group. The series includes four pure germinomas and one germinal non-germinoma. MRI and endoscopic exploration were necessary to define SPBT. Endocrine, ocular, and increased intracranial pressure syndromes were identified and related to the size of the tumors. Chemotherapy and radiotherapy were performed in all SPBT. Radical or partial resection of SPBT offered no benefits over biopsy. Prognosis for bifocal groups was similar to unifocal tumors of the same histological type. Complete remission without recurrence and mortality were achieved in all cases. SPBT seem to be an entity defined by a) one tumor in the suprasellar and another in the pineal region, b) GCT with predominance of PG, but not exclusively, and c) MRI and endoscopy without any dissemination. The presence of two tumors does not indicate dissemination; SPBT were non-disseminated but focal tumors, and spinal radiotherapy was not necessary.

  2. Destruction of solid tumors by immune cells

    Science.gov (United States)

    López, Álvaro G.; Seoane, Jesús M.; Sanjuán, Miguel A. F.

    2017-03-01

    The fractional cell kill is a mathematical expression describing the rate at which a certain population of cells is reduced to a fraction of itself. In order to investigate the fractional cell kill that governs the rate at which a solid tumor is lysed by a cell population of cytotoxic CD8+ T cells (CTLs), we present several in silico simulations and mathematical analyses. When the CTLs eradicate efficiently the tumor cells, the models predict a correlation between the morphology of the tumors and the rate at which they are lysed. However, when the effectiveness of the immune cells is decreased, the mathematical function fails to reproduce the process of lysis. This limit is thoroughly discussed and a new fractional cell kill is proposed.

  3. Xanthomatous Hypophysitis Mimicking a Pituitary Adenoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Laura Aste

    2010-01-01

    Full Text Available Background. Hypophysitis is an inflammatory disease of the pituitary gland that may mimic pituitary tumors clinically and radiologically. Case Description. We report a case of a xanthomatous hypophysitis initially diagnosed as pituitary adenoma. A 31-year-old woman presented with headache, diabetes insipidus, and amenorrhea. A head CT scan showed no intrasellar changes, while an MRI scan showed a sellar cystic mass. An endocrinological work up revealed mild hypocortisolism and diabetes insipidus (DI. Transsphenoidal surgery was performed. The intraoperative histological examination suggested a pituitary adenoma. The removed tissue showed central necrosis surrounded by accumulation of foamy cells and xanthomatous epithelioid cells. The patient made an uneventful postoperative recovery, Nevertheless, DI persisted and the adenohypophysis hypofunction did not recover. Conclusion. We describe an unusual inflammatory lesion of the pituitary gland mimicking an adenoma. A high level of clinical suspicion of inflammatory disorders is necessary for correct diagnosis and optimal management.

  4. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  5. "The Lower Threshold" phenomenon in tumor cells toward endogenous digitalis-like compounds: Responsible for tumorigenesis?

    Directory of Open Access Journals (Sweden)

    Heidrun Weidemann

    2012-01-01

    Full Text Available Since their first discovery as potential anti-cancer drugs decades ago, there is increasing evidence that digitalis-like compounds (DLC have anti-tumor effects. Less is known about endogenous DLC (EDLC metabolism and regulation. As stress hormones synthesized in and secreted from the adrenal gland, they likely take part in the hypothalamo-pituitary-adrenal (HPA axis. In a previous study, we revealed reduced EDLC concentrations in plasma and organs from immune-compromised animals and proposed that a similar situation of a deregulated HPA axis with "adrenal EDLF exhaustion" may contribute to tumorigenesis in chronic stress situations. Here, we put forward the hypothesis that a lowered EDLC response threshold of tumor cells as compared with normal cells increases the risk of tumorigenesis, especially in those individuals with reduced EDLC plasma concentrations after chronic stress exposure. We will evaluate this hypothesis by (a summarizing the effects of different DLC concentrations on tumor as compared with normal cells and (b reviewing some essential differences in the Na/K-ATPase of tumor as compared with normal cells (isoform pattern, pump activity, mutations of other signalosome receptors. We will conclude that (1 tumor cells, indeed, seem to have their individual "physiologic" EDLC response range that already starts at pmolar levels and (2 that individuals with markedly reduced (pmolar EDLC plasma levels are predisposed to cancer because these EDLC concentrations will predominantly stimulate the proliferation of tumor cells. Finally, we will summarize preliminary results from our department supporting this hypothesis.

  6. Receptor-mediated binding and uptake of GnRH agonist and antagonist by pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Jennes, L.; Stumpf, W.E.; Conn, P.M.

    1984-01-01

    The intracellular pathway of an enzyme resistant GnRH agonist (D- Lys6 -GnRH) conjugated to ferritin or to colloidal gold was followed in cultured pituitary cells. After an initial uniform distribution over the cell surface of gonadotropes, the electrondense marker was internalized, either individually or in small groups. After longer incubation times, the marker appeared in the lysosomal compartment and the Golgi apparatus, where it could be found in the vesicular as well as cisternal portion. In addition, the receptor-mediated endocytosis of the GnRH antagonist D-p-Glu1-D-Phe2-D-Trp3-D- Lys6 -GnRH was studied by light and electron microscopic autoradiography after 30 and 60 min of incubation to ensure uptake. At both time points, in in vitro as well as in vivo studies, silver grains were localized over cytoplasmic organelles of castration cells, including dilated endoplasmic reticulum, lysosomes, and clear vesicles. No consistent association with cell nuclei, mitochondria, or secretory vesicles could be observed. The results suggest that both agonist and antagonist are binding selectively to the plasma membrane of gonadotropes and subsequently are taken up via receptor-mediated endocytosis for degradation or possible action on synthetic processes.

  7. [Two autopsy cases of primary pituitary carcinoma].

    Science.gov (United States)

    Negishi, K; Suzuki, T; Masuda, Y; Masugi, Y; Teramoto, A; Ohama, E

    1988-05-01

    We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 垂体瘤手术及其并发症的防治%Clinical analysis of pituitary tumor operation and complication prevention

    Institute of Scientific and Technical Information of China (English)

    阳永东; 周晓坤; 杜怡庆; 王文波; 唐乐建

    2013-01-01

    Objective To retrospectively analyze and record the operation method of transsphenoidal approach for the treatment of pituitary tumors and complications,and put forward the prevention and treatment of complications strategies according to the clinical experience.Methods 256 cases of pituitary tumor patients with transsphenoidal operation resection of the tumor treatment,postoperative complications,and with Chen Longyi in 2010 reported results of a comparative analysis.Results 256 cases of patients with diabetes insipidus and cerebrospinal fluid leakage incidence was significantly lower than Chen Long-yi's Group (P < 0.01) ; other complications include water and electrolyte disorders,secondary hemorrhage,visual impairment worsened,hypothalamic function disorder,ophthalmoplegia and death,the two groups had no significant difference (P > 0.05).Conclusions More complications of pituitary tumor after operation,clinical should emphasize the operation method of operation,a clear approach,fit,and doctors should improve their own responsibility,to summarize the clinical experience,effective prevention and treatment of complications.%目的 分析经蝶入路治疗垂体瘤手术方法及并发症发生情况,提出并发症防治策略.方法 256例垂体瘤患者行经蝶入路手术切除肿瘤治疗,术后观察并发症发生情况,并与文献报道结果进行比较分析.结果 256例患者尿崩和脑脊液漏发生率明显低于文献报道(P<0.01);其他并发症包括水电解质紊乱、继发性出血、视力障碍加重、下丘脑功能紊乱、眼肌麻痹和死亡等,两组间比较差异无统计学意义(P>0.05).结论 垂体瘤手术后并发症较多,临床应强调手术操作方法、明确入路、适当填充,同时应有效防治并发症.

  9. NI-18MULTIMODAL NAVIGATION IN ENDOSCOPIC TRANS-SPHENOIDAL RESECTION OF PITUITARY TUMORS USING IMAGE-BASED VASCULAR AND CRANIAL NERVE SEGMENTATION: A PROSPECTIVE VALIDATION STUDY

    Science.gov (United States)

    Dolati, Parviz; Raber, Michael; Golby, Alexandra; Laws, Edward

    2014-01-01

    Trans-Sphenoidal surgery (TSS) is a well-known approach for treatment of pituitary tumors. However, in inexperienced hands, the risk of lateral misdirection and vascular damage, intraoperative CSF leakage, and optic nerve injury are all well-known complications of this procedure. This prospective study was conducted to validate the accuracy of image-based segmentation in localization of neurovascular structures during TSS. METHODS: Eight patients with pituitary tumor underwent preoperative 3TMRI, which included thin sectioned 3D space T2, 3D Time of Flight and MPRAGE sequences. Images were reviewed by an expert independent neuroradiologist. Imaging sequences were loaded in BrainLab iPlanNet (6/8) and Stryker (2/8) for segmentation and pre-op planning. After patient registration to the intra-op neuronavigation system and surgical exposure, each segmented neural or vascular element was validated by manual placement of the navigation probe. The pulses of the bilateral ICA were confirmed using micro-Doppler. RESULTS: Pre-operative segmentation of the ICA and cavernous sinus matched with the intra-operative endoscopic and micro-Doppler findings in all cases (Dice-coefficient =1). This information reassured surgeons regarding the lateral extent of bone removal at the sellar floor and the limits of lateral explorations. Perfect correspondence between image-based segmentation and endoscopic view was also found at the surface of the tumor and tumor-normal gland interfaces. This helped in preventing unnecessary removal of the normal pituitary gland. Image-guidance helped surgeon to localize the optic nerve and chiasm in 63% of case and Diaphragma sella in 50% of cases, which helped to determine the limits of upward exploration and decrease the risk of CSF leakage. CONCLUSION: Image-based pre-operative vascular and neural element segmentation especially with 3D reconstruction is highly informative preoperatively and helps young and inexperienced neurosurgeons to prevent

  10. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar

    2011-01-01

    Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...... that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 appears to be dispensable for its tumor-promoting effect. Interestingly, we demonstrate that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence...... tumor progression, but that ADAM12 expression by tumor cells is necessary for tumor progression in these mice. This finding is consistent with our observation that in human breast carcinoma ADAM12 is almost exclusively located in tumor cells and only rarely seen in the tumor-associated stroma. We...

  11. Characterization of cell suspensions from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.

    1985-07-10

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs.

  12. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  13. Shift of the pituitary stalk in intrasellar pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Jusuke; Tokiguchi, Susumu; Nakamori, Akitoshi (Niigata Univ. (Japan). School of Medicine); Watanabe, Akira; Yokoyama, Motoharu

    1982-08-01

    Fifty-one patients from a group of 344 patients undergoing the evaluation of intrasellar or parasellar tumors were diagnosed on CT as having an intrasellar pituitary adenoma. Axial transverse sections were performed at -10/sup 0/ to Reid's basal line, using 1.5-mm-thick slices and sagittal and coronal reformation. Of these 51 patients, 17 showed a shift of the pituitary stalk. The area where a tumor was thought to be located within the sella turcica on preoperative CT became defective on CT after transsphenoidal surgery in all cases. Histological verification was obtained in all cases. Also, the shift of the pituitary stalk was normalized or markedly improved after surgery in all cases. In functioning tumors, all cases except two showed an endocrinologically normal state or a marked improvement after transsphenoidal surgery. On the basis of the above-mentioned facts, it was concluded that the shift of the pituitary stalk in intrasellar pituitary adenomas indicated the evidence of a mass and its location in the sella turcica. However, a shift of the pituitary stalk was also observed under other conditions, such as empty sella and tuberculum sellae meningioma, and so it is not a pathognomonic finding in intrasellar pituitary adenomas.

  14. Ovarian steroid cell tumors: sonographic characteristics.

    Science.gov (United States)

    Monteagudo, A; Heller, D; Husami, N; Levine, R U; McCaffrey, R; Timor-Tritsch, I E

    1997-10-01

    The goal of the gynecologist is to detect ovarian tumors in their earliest stages. Small virilizing tumors, which barely affect the size of the ovaries, are such lesions. Since the introduction of transvaginal sonography it is technically possible to detect small intraovarian neoplasms. Three cases of virilizing steroid cell tumors in postmenopausal women with ovarian volumes just exceeding the normal sizes for age are presented. High-frequency transvaginal ultrasound and color Doppler studies to measure flow parameters were used. These small tumors had different echogenicity from the surrounding ovarian tissue and two had low impedance-to-flow values. Gray-scale transvaginal sonography combined with color Doppler studies can make the diagnosis of small steroid cell tumors easier and, at times, better than other, more costly imaging modalities.

  15. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  16. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    Science.gov (United States)

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  17. Prevention Strategies of Pituitary Tumor Surgery and Postoperative Complications%垂体瘤手术与术后并发症的防治策略

    Institute of Scientific and Technical Information of China (English)

    陈爱明

    2016-01-01

    Objective Explore pituitary tumor surgery, treatment and prevention methods of postoperative complications.Methods 20 patients diagnosed as pituitary tumor surgery patients in parallel, take transsphenoidal surgery under a microscope to analyze the effect of surgery and postoperative complications.Results The group of 20 patients with total resection of 13 cases, accounting for 65.0%, partially cut two cases, accounting for 10.0%, subtotal ifve cases, accounting for 25.0%, diabetes insipidus, electrolyte imbalance, decreased vision in 1 case, 1 case of hypopituitarism, cerebrospinal fluid rhinorrhea one case, two cases of other complications.Conclusion Microscope Transsphenoidal treatment of pituitary tumor effect is remarkable, relieve symptoms signiifcantly higher total resection rate, fewer complications, can be used as the ifrst choice of treatment.%目的:探究垂体瘤手术的治疗效果及术后并发症的防治方法。方法选择20例诊断为垂体瘤并行手术的患者,采取显微镜下经蝶入路手术治疗,分析手术效果及术后并发症情况。结果本组20例患者全切13例,占65.0%,部分切2例,占10.0%,次全切5例,占25.0%;尿崩症、电解质紊乱、视力下降各1例,垂体功能低下1例,脑脊液鼻漏1例,其他并发症2例。结论显微镜经蝶入路手术治疗垂体瘤效果显著,患者的症状缓解显著,全切率较高,并发症少,可作为治疗的首选方案。

  18. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

    Science.gov (United States)

    Ibáñez-Costa, Alejandro; Gahete, Manuel D; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D; Dieguez, Carlos; Castaño, Justo P; Luque, Raúl M

    2015-03-04

    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.

  19. Escape from Tumor Cell Dormancy

    Science.gov (United States)

    2012-10-01

    Pouliot, K. L. Stanley, J. Chia , J. M. Moseley, D. K. Hards and R. L. Anderson: Tumor-specific expression of alphavbeta3 integrin promotes...deep, measured by confocal imaging of microwells filled with 20-mm-diameter fluores - cent beads (Fig. 1). Evaluation of mechanical properties of PEG...

  20. [Sertoli cell tumor of the testis].

    Science.gov (United States)

    Hita Rosino, E; López Hidalgo, J; Mellado Mesa, P; Olivar Buera, M

    2001-01-01

    Sertoli cell tumors (TCS) derivated from sex-cord estroma cells, are an uncommon variety of testicles neoplasms. A 66 year-old patient that came to the consultation for an increased scrotum of size present. Ultrasound viewed a hipoecoic nodule capable with testicular tumor, more secondary hidrocele. After undergoing the standard treatment, by means of groin radical orchiectomy, its pathologic analysis identified the lesion as Sertoli cell tumor conventional. The pathologic features that best correlate with a clinically benign course are as follows: a lower size tumor to 5 cm, mild nuclear atypia, a mitotic rate of less than 5 mitosis per 10 high power fields, and absent necrosis. Our case presented with these features. Follow-up of these neoplasms should be prolonged by the unusual of its presentation and a small percentage of cases are clinically malignant.

  1. Radiosensitivity of tumor cells. Oncogenes and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Peltenburg, L. T. C. [Leiden Univ., Leiden (Netherlands). Dept. of Clinical Oncology

    2000-12-01

    The success of treatment of cancer patients by radiotherapy largely depends on tumor radiosensitivity. Several molecular factors that determine the sensitivity of tumor cells to ionizing radiation have been identified during the last couple of years. Some of these factors are known as oncogenes and tumor suppressor genes. This review focuses on the influence of some of these molecular factors on a major determinant of radiosensitivity: i. e. programmed cell death or apoptosis. The crucial molecular step in ionizing radiation-induced apoptosis is the release of mitochondrial cytochrome c into the cell's cytosol. The ways the tumor suppressor protein p53, as well as the oncogenes ras and raf, c-myc and Bcl-2 can influence this process at different stages are presented. As will be discussed, the result of activation of an oncoprotein on tumor radiosensitivity depends on its mechanism of action and on the presence of other (oncogenic) factors, since complex interactions among many molecular factors determine the delicate balance between cell proliferation and cell death. The ongoing identification and characterization of factors influencing apoptosis will eventually make it possible to predict tumor radiosensitivity and thereby improve cancer treatment.

  2. Pituitary Adenoma Segmentation

    CERN Document Server

    Egger, Jan; Kuhnt, Daniela; Freisleben, Bernd; Nimsky, Christopher

    2011-01-01

    Sellar tumors are approximately 10-15% among all intracranial neoplasms. The most common sellar lesion is the pituitary adenoma. Manual segmentation is a time-consuming process that can be shortened by using adequate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm we developed recently in previous work where the novel segmentation scheme was successfully used for segmentation of glioblastoma multiforme and provided an average Dice Similarity Coefficient (DSC) of 77%. This scheme is used for automatic adenoma segmentation. In our experimental evaluation, neurosurgeons with strong experiences in the treatment of pituitary adenoma performed manual slice-by-slice segmentation of 10 magnetic resonance imaging (MRI) cases. Afterwards, the segmentations were compared with the segmentation results of the proposed method via the DSC. The average DSC for all data sets was 77.49% +/- 4.52%. Compared with a manual segmentation that took, on the...

  3. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

    Directory of Open Access Journals (Sweden)

    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  4. Characterization of tumor cells and stem cells by differential nuclear methylation imaging

    Science.gov (United States)

    Tajbakhsh, Jian; Wawrowsky, Kolja A.; Gertych, Arkadiusz; Bar-Nur, Ori; Vishnevsky, Eugene; Lindsley, Erik H.; Farkas, Daniel L.

    2008-02-01

    DNA methylation plays a key role in cellular differentiation. Aberrant global methylation patterns are associated with several cancer types, as a result of changes in long-term activation status of up to 50% of genes, including oncogenes and tumor-suppressor genes, which are regulated by methylation and demethylation of promoter region CpG dinucleotides (CpG islands). Furthermore, DNA methylation also occurs in nonisland CpG sites (> 95% of the genome), present once per 80 dinucleotides on average. Nuclear DNA methylation increases during the course of cellular differentiation while cancer cells usually show a net loss in methylation. Given the large dynamic range in DNA methylation load, the methylation pattern of a cell can provide a valuable distinction as to its status during differentiation versus the disease state. By applying immunofluorescence, confocal microscopy and 3D image analysis we assessed the potential of differential nuclear distribution of methylated DNA to be utilized as a biomarker to characterize cells during development and when diseased. There are two major fields that may immediately benefit from this development: (1) the search for factors that contribute to pluripotency and cell fate in human embryonic stem cell expansion and differentiation, and (2) the characterization of tumor cells with regard to their heterogeneity in molecular composition and behavior. We performed topological analysis of the distribution of methylated CpG-sites (MeC) versus heterochromatin. This innovative approach revealed significant differences in colocalization patterns of MeC and heterochromatin-derived signals between undifferentiated and differentiated human embryonic stem cells, as well as untreated AtT20 mouse pituitary tumor cells compared to a subpopulation of these cells treated with 5-azacytidine for 48 hours.

  5. Non-pituitary origin sellar tumours mimicking pituitary macroadenomas

    Energy Technology Data Exchange (ETDEWEB)

    Abele, T.A., E-mail: travaus@gmail.com [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States); Yetkin, Z.F.; Raisanen, J.M.; Mickey, B.E.; Mendelsohn, D.B. [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States)

    2012-08-15

    Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

  6. Osteoclastic giant cell tumor of the pancreas: an immunohistochemical study

    DEFF Research Database (Denmark)

    Dizon, M A; Multhaupt, H A; Paskin, D L

    1996-01-01

    A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor.......A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor....

  7. Gene expression profiling of pituitary melanotrope cells during their physiological activation.

    Science.gov (United States)

    Kuribara, Miyuki; van Bakel, Nick H M; Ramekers, Dyan; de Gouw, Daan; Neijts, Roel; Roubos, Eric W; Scheenen, Wim J J M; Martens, Gerard J M; Jenks, Bruce G

    2012-01-01

    The pituitary melanotrope cells of the amphibian Xenopus laevis are responsible for the production of the pigment-dispersing peptide α-melanophore-stimulating hormone, which allows the animal to adapt its skin color to its environment. During adaptation to a dark background the melanotrope cells undergo remarkable changes characterized by dramatic increases in cell size and secretory activity. In this study we performed microarray mRNA expression profiling to identify genes important to melanotrope activation and growth. We show a strong increase in the expression of the immediate early gene (IEG) c-Fos and of the brain-derived neurotrophic factor gene (BDNF). Furthermore, we demonstrate the involvement of another IEG in the adaptation process, Nur77, and conclude from in vitro experiments that the expression of both c-Fos and Nur77 are partially regulated by the adenylyl cyclase system and calcium ions. In addition, we found a steady up-regulation of Ras-like product during the adaptation process, possibly evoked by BDNF/TrkB signaling. Finally, the gene encoding the 105-kDa heat shock protein HSPh1 was transiently up-regulated in the course of black-background adaptation and a gene product homologous to ferritin (ferritin-like product) was >100-fold up-regulated in fully black-adapted animals. We suggest that these latter two genes are induced in response to cellular stress and that they may be involved in changing the mode of mRNA translation required to meet the increased demand for de novo protein synthesis. Together, our results show that microarray analysis is a valuable approach to identify the genes responsible for generating coordinated responses in physiologically activated cells.

  8. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  9. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  10. Myeloid cells contribute to tumor lymphangiogenesis.

    Science.gov (United States)

    Zumsteg, Adrian; Baeriswyl, Vanessa; Imaizumi, Natsuko; Schwendener, Reto; Rüegg, Curzio; Christofori, Gerhard

    2009-09-17

    The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation.

  11. Myeloid cells contribute to tumor lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Adrian Zumsteg

    Full Text Available The formation of new blood vessels (angiogenesis and lymphatic vessels (lymphangiogenesis promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation.

  12. Unusual mixed gangliocytoma-pituitary adenoma in sellar region

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    Jie-tian JIN

    2016-10-01

    Full Text Available Background The presence of ganglion cells within an endocrine pituitary adenoma in sellar region is rare, and is usually diagnosed as "mixed gangliocytoma-pituitary adenoma". Due to lack of radiological characteristics, it is very difficult to make an accurate diagnosis preoperatively. Herein we describe one case of unusual mixed gangliocytoma - growth hormone (GH secreting pituitary adenoma in sellar region and review related literatures, so as to summarize the clinicopathological characteristics and improve the diagnosis and differential diagnosis of this tumor. Methods and Results A 28 - year - old female presented with headache and blurred vision for 8 months. She also complained of acromegaly and amenorrhea. Head CT and MRI examinations showed a sellar and suprasellar mass with clear boundary compressing the optic chiasm and buttom of the third ventricle. The mass exhibited isointense signal or mild hypointensity on T1WI and mild hyperintensity on T2WI with heterogeneous enhancement on the contrast MRI. The tumor was removed totally. The histological sections demonstrated two parts of intermixed areas. One part of areas was marked by a proliferation of scattered gangliocyte - like cells arranged in a fibrillary background. Other areas were marked by a sheet - like or locally papillary proliferation of round and oval cells. Immunohistochemically, cytoplasm of gangliocyte-cells were diffusely positive for synaptophysin (Syn, and negative for adenohypophysial hormones; cytoplasm of round and oval cells were diffusely positive for Syn, and almost 30% cells were positive for GH, and negative for other neurohypophysial hormones. A final diagnosis of mixed gangliocytoma-GH secreting pituitary adenoma in sellar region (WHO grade Ⅰ was made. The patient did not receive postoperatively adjuvant therapy and was followed-up for one year, without any neurological deficit or signs of recurrence. Conclusions Mixed gangliocytoma - pituitary

  13. Metastatic pituitary carcinoma: a case report and review of literature

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    ZHANG Shang-fu

    2013-02-01

    Full Text Available Background As a kind of rare tumor, metastatic pituitary carcinoma is very difficult to diagnose clinically and is easy to be misdiagnosed. This article aims to discuss the clinical manifestations and histopathological features of this tumor. Methods The clinical presentations, histopathological features and immunophenotype were studied in one case of poorly differentiated lung adenocarcinoma metastatic to pituitary gland, and related literature was reviewed. Results A 47-year-old woman mainly presented with faint, headache and blurred vision. CT scan demonstrated abnormal signals in suprasellar cistern. During the resection, the tumor could be seen locating in sellar region, the size of which was about 2 cm × 1 cm × 1 cm. Histopathological examination revealed that the structure of pituitary gland was damaged and the tumor was composed of atypical round or oval cells arranged in nest or glandular patterns, in which a number of enlarged plump tumor cells contained abundant eosinophilic cytoplasm with eccentrical caryogenesis. The immunohistochemistry showed that epithelial membrane antigen (EMA, pan cytokeratin (PCK, thyroid transcription factor-1 (TTF-1 and cytokeratin 7 (CK7 were positive in tumor cells with Ki-67 labeling index being 15%, but chromogranin (CgA, cancer embryo antigen (CEA, human chorionic gonadotropin (hCG, placental alkaline phosphatase (PLAP, CD117, leukocyte common antigen (LCA, CD30, anaplastic lymphoma kinase-1 (ALK-1 were negative in tumor cells. After operation the patient received treatment with levothyroxine sodium and γ knife, but died 4 months later. Conclusion Histopathological examination and immunohistochemistry can confirm the diagnosis of metastatic pituitary carcinoma and locate the primary lesion. Postoperative comprehensive therapy is necessary.

  14. Cytomorphology of metastatic pituitary carcinoma to the bone.

    Science.gov (United States)

    Chandler, Christopher M; Lin, Xiaoqi

    2017-03-07

    Metastatic pituitary carcinoma to bone is rare. In this report, we present a case of a 59-year-old female with recurrent pituitary adenoma of the sparsely granulated somatotroph subtype with metastasis to a few bony sites 10 years later. Needle core biopsy (NCB) with touch preparations was performed on a 5 mm lesion in left ilium. Diff-Quik stained NCB touch preparation slides showed a few loosely cohesive epithelial polygonal cells that were arranged in nests or acini, or singly, had scant vacuolated cytoplasm and eccentrically located round nuclei (plasmacytoid) with slight nuclear pleomorphism, fine granular chromatin, conspicuous nucleoli, and smooth nuclear membrane. Trilineage hematopoietic cells of bone marrow were also appreciated in the background. H&E stained core sections showed fragments of bone and bone marrow with nests of bland epithelial cells with similar cytomorphology as seen in NCB touch preparation slides. The tumor cells were immunoreactive for juxtanuclear dot-like staining of pan-cytokeratin (CAM 5.2 and AE1/AE3) (a specific feature), neuroendocrine markers (CD56, synaptophysin, and chromogranin. Additionally, scattered cells were immunoreactive for growth hormone. Molecular test showed that tumor cells were negative for the promoter methylation of O-6-Methylguanine-DNA Methyltransferase (MGMT). Final diagnosis of metastatic pituitary carcinoma was rendered. Morphology of metastatic pituitary carcinoma, its differential, clinical presentation and treatment were discussed. Diagn. Cytopathol. 2017. © 2017 Wiley Periodicals, Inc.

  15. Pituitary adenylate cyclase activating polypeptide modulates catecholamine storage and exocytosis in PC12 cells.

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    Yan Dong

    Full Text Available A number of efforts have been made to understand how pituitary adenylate cyclase activating polypeptide (PACAP functions as a neurotrophic and neuroprotective factor in Parkinson's disease (PD. Recently its effects on neurotransmission and underlying mechanisms have generated interest. In the present study, we investigate the effects of PACAP on catecholamine storage and secretion in PC12 cells with amperometry and transmission electron microscopy (TEM. PACAP increases quantal release induced by high K+ without significantly regulating the frequency of vesicle fusion events. TEM data indicate that the increased volume of the vesicle is mainly the result of enlargement of the fluidic space around the dense core. Moreover, the number of docked vesicles isn't modulated by PACAP. When cells are acutely treated with L-DOPA, the vesicular volume and quantal release both increase dramatically. It is likely that the characteristics of amperometric spikes from L-DOPA treated cells are associated with increased volume of individual vesicles rather than a direct effect on the mechanics of exocytosis. Treatment with PACAP versus L-DOPA results in different profiles of the dynamics of exocytosis. Release via the fusion pore prior to full exocytosis was observed with the same frequency following treatment with PACAP and L-DOPA. However, release events have a shorter duration and higher average current after PACAP treatment compared to L-DOPA. Furthermore, PACAP reduced the proportion of spikes having rapid decay time and shortened the decay time of both fast and slow spikes. In contrast, the distributions of the amperometric spike decay for both fast and slow spikes were shifted to longer time following L-DOPA treatment. Compared to L-DOPA, PACAP may produce multiple favorable effects on dopaminergic neurons, including protecting dopaminergic neurons against neurodegeneration and potentially regulating dopamine storage and release, making it a promising

  16. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  17. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.

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    Murakami,Kazuharu

    1984-08-01

    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  18. Gangliosides regulate tumor cell adhesion to collagen.

    Science.gov (United States)

    Kazarian, Tamara; Jabbar, Adnan A; Wen, Fei-Qui; Patel, Dharmesh A; Valentino, Leonard A

    2003-01-01

    The ability of tumor cells to adhere to extracellular matrix proteins is critical for migration and invasion. The factors that regulate tumor cell adhesion are poorly characterized. Gangliosides promote platelet adhesion and may also play a role in the adhesion of other cell types. We hypothesized that pharmacological depletion of membrane gangliosides from adherent cells would abrogate adhesion to collagen and promote migration and invasion. To test these hypotheses, LA-N1 neuroblastoma cells, which avidly adhere to collagen and are rich with membrane gangliosides (43.69 nmol/10(8) cells), were cultured in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl. Endogenous gangliosides were reduced by 98% (0.76 nmol/10(8) cells) and adhesion to collagen decreased by 67%. There were no changes in cell morphology, viability, proliferation rate or apoptosis. Pre-incubation of ganglioside-depleted cells in conditioned medium from control cells restored adhesion to collagen (0.45 +/- 0.002), comparable to that of control cells (0.49 +/- 0.035). Similarly, pre-incubation of ganglioside-depleted cells with purified GD2 completely restored adhesion in a concentration-dependent manner. When LA-N1 cells were cultured with retinoic acid, a biological response modifier known to increase endogenous gangliosides, adhesion to collagen increased. Next, we questioned whether changes in adhesion would be reflected as changes in migration and invasion. Cells depleted of endogenous cellular gangliosides migrated more than control cells. Finally, control cells replete with their endogenous gangliosides demonstrated less invasive potential than control cells. The data demonstrate that endogenous tumor gangliosides increase neuroblastoma cell adhesion to collagen and reduce migration and invasion in vitro.

  19. Pituitary infarction

    Science.gov (United States)

    ... during or right after childbirth, it is called Sheehan syndrome . This is a very rare condition. Risk factors ... commonly, pituitary dysfunction may appear more slowly. In Sheehan syndrome, for example, the first symptom may be a ...

  20. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

    Science.gov (United States)

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

    2017-02-09

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca(2+) signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca(2+) concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca(2+) concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca(2+) signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

  1. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

    Science.gov (United States)

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

    2017-01-01

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

  2. Giant cell tumor of bone: Multimodal approach

    Directory of Open Access Journals (Sweden)

    Gupta A

    2007-01-01

    Full Text Available Background: The clinical behavior and treatment of giant cell tumor of bone is still perplexing. The aim of this study is to clarify the clinico-pathological correlation of tumor and its relevance in treatment and prognosis. Materials and Methods: Ninety -three cases of giant cell tumor were treated during 1980-1990 by different methods. The age of the patients varied from 18-58 yrs with male and female ratio as 5:4. The upper end of the tibia was most commonly involved (n=31, followed by the lower end of the femur(n=21, distal end of radius(n=14,upper end of fibula (n=9,proximal end of femur(n=5, upper end of the humerus(n=3, iliac bone(n=2,phalanx (n=2 and spine(n=1. The tumors were also encountered on uncommon sites like metacarpals (n=4 and metatarsal(n=1. Fifty four cases were treated by curettage and bone grafting. Wide excision and reconstruction was performed in twenty two cases . Nine cases were treated by wide excision while primary amputation was performed in four cases. One case required only curettage. Three inaccessible lesions of ilium and spine were treated by radiotherapy. Results: 19 of 54 treated by curettage and bone grafting showed a recurrence. The repeat curettage and bone grafting was performed in 18 cases while amputation was done in one. One each out of the cases treated by wide excision and reconstruction and wide excision alone recurred. In this study we observed that though curettage and bone grafting is still the most commonly adopted treatment, wide excision of tumor with reconstruction has shown lesser recurrence. Conclusion: For radiologically well-contained and histologically typical tumor, curettage and autogenous bone grafting is the treatment of choice . The typical tumors with radiologically deficient cortex, clinically aggressive tumors and tumors with histological Grade III should be treated by wide excision and reconstruction.

  3. The pathophysiology of pituitary adenomas.

    Science.gov (United States)

    Dworakowska, Dorota; Grossman, Ashley B

    2009-10-01

    The pathogenesis of tumour formation in the anterior pituitary has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain elusive. Most pituitary tumours are sporadic, but some arise as a component of genetic syndromes such as the McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, the most recently described, a MEN1-like phenotype (MEN4) and pituitary adenoma predisposition syndromes. Some specific genes have been identified that predispose to pituitary neoplasia (GNAS, MEN1, PRKAR1A, CDKN1B and AIP), but these are rarely involved in the pathogenesis of sporadic tumours. Mutations of tumour suppressor genes or oncogenes, as seen in more common cancers, do not seem to play an important role in the great majority of pituitary adenomas. The pituitary tumour transforming gene (PTTG; securin) was the first transforming gene found to be highly expressed in pituitary tumour cells, and seems to play an important role in the process of oncogenesis. Many tumour suppressor genes, especially those involved in the regulation of the cell cycle, are under-expressed, most often by epigenetic modulation - usually promoter hypermethylation - but the regulator of these co-ordinated series of methylations is also unclear. Cell signalling abnormalities have been identified in pituitary tumours, but their genetic basis is unknown. Both Raf/MEK/ERK and PI3K/Akt/mTOR pathways are over-expressed and/or over-activated in pituitary tumours: these pathways share a common root, including initial activation related to the tyrosine kinase receptor, and we speculate that a change to these receptors or their relationship to membrane matrix-related proteins may be an early event in pituitary tumourigenesis.

  4. Ultrasound features of orbital granular cell tumor.

    Science.gov (United States)

    Ayres, Bernadete; Miller, Neil R; Eberhart, Charles G; Dibernardo, Cathy W

    2009-01-01

    The authors report the echographic characteristics of a rare orbital granular cell tumor and correlate these findings with histopathology. A 56-year-old woman presented with proptosis. Complete ophthalmic and ultrasound examinations were performed. Ultrasound revealed an oval, well-outlined orbital mass in the intraconal space with low-medium reflectivity and regular internal structure. An orbitotomy with complete excision of the tumor was performed. Histopathologic evaluation showed sheets and nests of cells with abundant eosinophilic and granular cytoplasm in a uniform distribution throughout the lesion. The echographic characteristics correlated well with the morphologic surgical findings and the histologic architecture. This is the first report describing the echographic characteristics of orbital granular cell tumor.

  5. In vivo photolabeling of tumor-infiltrating cells reveals highly regulated egress of T-cell subsets from tumors.

    Science.gov (United States)

    Torcellan, Tommaso; Hampton, Henry R; Bailey, Jacqueline; Tomura, Michio; Brink, Robert; Chtanova, Tatyana

    2017-05-30

    Immune therapy is rapidly gaining prominence in the clinic as a major weapon against cancer. Whereas much attention has been focused on the infiltration of tumors by immune cells, the subsequent fate of these infiltrates remains largely unexplored. We therefore established a photoconversion-based model that allowed us to label tumor-infiltrating immune cells and follow their migration. Using this system, we identified a population of tumor-experienced cells that emigrate from primary tumors to draining lymph nodes via afferent lymphatic vessels. Although the majority of tumor-infiltrating cells were myeloid, T cells made up the largest population of tumor-egressing leukocytes. Strikingly, the subset composition of tumor-egressing T cells was greatly skewed compared with those that had infiltrated the tumor and those resident in the draining lymph node. Some T-cell subsets such as CD8(+) T cells emigrated more readily; others including CD4(-)CD8(-) T cells were preferentially retained, suggesting that specific mechanisms guide immune cell egress from tumors. Furthermore, tumor-egressing T cells were more activated and displayed enhanced effector function in comparison with their lymph node counterparts. Finally, we demonstrated that tumor-infiltrating T cells migrate to distant secondary tumors and draining lymph nodes, highlighting a mechanism whereby tumor-experienced effector T cells may mediate antitumor immunity at metastatic sites. Thus, our results provide insights into migration and function of tumor-infiltrating immune cells and the role of these cells in tumor immunity outside of primary tumor deposits.

  6. Cirurgia da hipófise por via trans-esfenoidal sob controle radiofluoroscópico e microdissecção novo tratamento da retinopatia diabética, tumores selares e neoplasias endocrinodependentes The surgery of the pituitary gland using a transphenoidal approach under radiofluoroscopic control and microdisection: a new treatment for diabetic retinopathy, pituitary tumors and endocrinodependent growths

    Directory of Open Access Journals (Sweden)

    Jules Hardy

    1968-03-01

    Full Text Available É apresentada nova técnica para a ablação total ou seletiva da hipófise utilizando via de acesso trans-esfenoidal, controle radiofluoroscópico e microdissecção, com traumatismo desprezível às estruturas circunvizinhas. Os autores comentam as aplicações do método à prática neurocirúrgica, relatando parte de uma série de mais 140 casos já operados. São discutidos os resultados obtidos no tratamento de 17 casos de retinopatia diabética, em 11 dos quais apenas o lobo anterior da hipófise foi removido, assim como aqueles obtidos na exérese de 20 casos de tumores selares. As indicações da hipofisectomia por via trans-esfenoidal no controle da sintomatologia das neoplasias endòcrinodependentes é estudada à luz dos resultados obtidos em 17 casos, sendo os resultados comparados com casos nos quais foi feita a implantação selar de ítrio90. As complicações operatorias em relação às três entidades nosológicas acima estudadas são também analisadas. Os autores salientam que a técnica descrita constitui, no presente estado das técnicas neurocirúrgicas utilizadas para a produção de uma insuficiência hipofisária duradoura, a intervenção de escolha.A new neurosurgical technique for the partial or total exéresis of the pituitary gland, using a transphenoidal approach under radiofluoroscopic control and microdisection is described. Part of a series of more than 140 cases operated upon by this method is reported. Results obtained in the treatment of diabetic retinopathy in 17 cases, 11 of which had only the pars anterior removed, are discussed. The applications of the transphenoidal route in 20 cases of pituitary fossa tumors are analysed. The indications of this type of operation in the management of endocrinodependent cancer is studied in 17 cases and compared with the results of 36 cases submitted to implant of Yttrium90 in the sella turcica. The operative complications following transphenoidal exéresis of the

  7. Pituitary apoplexy

    Directory of Open Access Journals (Sweden)

    Salam Ranabir

    2011-01-01

    Full Text Available Pituitary apoplexy is rare endocrine emergency which can occur due to infarction or haemorrhage of pituitary gland. This disorder most often involves a pituitary adenoma. Occasionally it may be the first manifestation of an underlying adenoma. There is conflicting data regarding which type of pituitary adenoma is prone for apoplexy. Some studies showed predominance of non-functional adenomas while some other studies showed a higher prevalence in functioning adenomas amongst which prolactinoma have the highest risk. Although pituitary apoplexy can occur without any precipitating factor in most cases, there are some well recognizable risk factors such as hypertension, medications, major surgeries, coagulopathies either primary or following medications or infection, head injury, radiation or dynamic testing of the pituitary. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic instability may be result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI should be performed in suspected cases. Intravenous fluid and hydrocortisone should be administered after collection of sample for baseline hormonal evaluation. Earlier studies used to advocate urgent decompression of the lesion but more recent studies favor conservative approach for most cases with surgery reserved for those with deteriorating level of consciousness or increasing visual defect. The visual and endocrine outcomes are almost similar with either surgery or conservative management. Once the acute phase is over, patient should be re-evaluated for hormonal deficiencies.

  8. Immunosuppressive cells in tumor immune escape and metastasis.

    Science.gov (United States)

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

  9. Oriented collagen fibers direct tumor cell intravasation

    KAUST Repository

    Han, Weijing

    2016-09-24

    In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

  10. The inactivating K+ current in GH3 pituitary cells and its modification by chemical reagents.

    Science.gov (United States)

    Oxford, G S; Wagoner, P K

    1989-01-01

    1. Whole-cell and single-channel recording techniques were applied to the study of the permeability and gating of inactivating K+ channels from clonal pituitary cells. 2. The cation selectivity sequence (measured from reversal potentials) for the channels underlying the inactivating K+ current was Tl+ greater than K+ greater than Rb+ greater than NH4+. The conductance sequence (determined from current amplitudes) was K+ = Tl+ greater than Rb+ greater than NH4+. 3. The inactivating current (IK(i] which was blocked by 4-aminopyridine (4-AP), activated at voltages more positive than -40 mV and half-inactivated at that voltage. Inactivation proceeded as the sum of two exponentials with mean time constants of 21 and 82 ms. Deactivation followed a single-exponential time course. 4. Recovery from inactivation was slow, voltage dependent and multi-exponential, taking more than 50 s near the cell's resting potential. 5. The magnitudes of outward current and of slope conductance increased as the concentration of external K+ was increased. 6. On-cell and outside-out membrane patches revealed minicurrents with gating and pharmacological properties identical to whole-cell currents. Single channels with inactivating characteristics, while rarely observed, had an average slope conductance of 6-8 pS. 7. Intracellular application of the disulphonic stilbene derivative, SITS, and the protein-modifying reagent, N-bromoacetamide (NBA), at concentrations of 0.2-1 mM for several tens of minutes dramatically slowed the decay (inactivation) of K+ currents and caused coincident increases in the magnitude of outward IK(i). 8. Extracellular application of NBA at much lower concentrations (1-100 microM) and much shorter exposure times (1-30 s) also slowed inactivation. This effect was reversible for brief applications at low doses, but became irreversible after longer exposures. 9. Both internal and external NBA shifted the steady-state inactivation-voltage relation by +10 mV and reduced

  11. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors.

    Science.gov (United States)

    Wyckoff, Jeffrey B; Wang, Yarong; Lin, Elaine Y; Li, Jiu-feng; Goswami, Sumanta; Stanley, E Richard; Segall, Jeffrey E; Pollard, Jeffrey W; Condeelis, John

    2007-03-15

    Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.

  12. Recruiting of somatotroph cells after combined somatostatin, GHRH and growth hormone (GH) secretagogue stimulation in a study of pituitary GH reserve in prepuberal female rats

    OpenAIRE

    Jiménez Reina, L.; García-Martínez, E.; Rojas, J.P.; Cañete, M.D.; G. Bernal; Cañete, R.

    2006-01-01

    Diagnostic confirmation of growth hormone (GH) deficiency in children and adults is based on stimulation tests designed to assess the pituitary reserve by measuring the amount of GH released into the bloodstream; however, the results obtained by this means cannot provide any direct indication of the amount of GH actually produced by pituitary somatotroph cells. The present paper sought to test the hypothesis that release of GH following administration of sp...

  13. Management of desmoplastic small round cell tumor.

    Science.gov (United States)

    Hayes-Jordan, Andrea; LaQuaglia, Michael P; Modak, Shakeel

    2016-10-01

    Desmoplastic small round cell tumor (DSRCT) is a soft tissue sarcoma of mesenchymal cell origin that typically presents with multiple intra-abdominal tumors and exhibits a multi-phenotypic pattern of immunohistochemical staining. The specific organ or tissue type of origin has yet to be identified. DSRCT rarely arises as a singular tumor in the abdomen; in most cases, there are dozens to hundreds of abdominal peritoneal tumors that are detected on diagnosis. One very large dominant mass is usually present in the omentum, with an additional one or two large conglomerates of tumors in the pelvis and right peritoneum, respectively. Despite an often overwhelmingly large number of abdominal tumors, symptoms of bowel obstruction are rare. Ascites may be present. In late stages, pleural effusions, pleural implants, mediastinal adenopathy, supraclavicular adenopathy, or bone metastasis may be present. With this challenging disease, multidisciplinary therapy, including aggressive surgery, is warranted. This review will address DSRCT biology and treatment options and discuss outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Notch signaling-mediated cell-to-cell interaction is dependent on E-cadherin adhesion in adult rat anterior pituitary.

    Science.gov (United States)

    Batchuluun, Khongorzul; Azuma, Morio; Yashiro, Takashi; Kikuchi, Motoshi

    2016-12-10

    The rat anterior pituitary is composed of hormone-producing cells, non-hormone-producing cells (referred to as folliculostellate cells) and marginal layer cells. In the adult rat, progenitor cells of hormone-producing cells have recently been reported to be maintained within this non-hormone-producing cell population. In tissue, non-hormone-producing cells construct homophilic cell aggregates by the differential expression of the cell adhesion molecule E-cadherin. We have previously shown that Notch signaling, a known regulator of progenitor cells in a number of organs, is activated in the cell aggregates. We now investigate the relationship between Notch signaling and E-cadherin-mediated cell adhesion in the pituitary gland. Immunohistochemically, Notch signaling receptor Notch2 and the ligand Jagged1 were localized within E-cadherin-positive cells in the marginal cell layer and in the main part of the anterior lobe, whereas Notch1 was localized in E-cadherin-positive and -negative cells. Activation of Notch signaling within E-cadherin-positive cells was confirmed by immunostaining of the Notch target HES1. Notch2 and Jagged1 were always co-localized within the same cells suggesting that homologous cells have reciprocal effects in activating Notch signaling. When the E-cadherin function was inhibited by exposure to a monoclonal antibody (DECMA-1) in primary monolayer cell culture, the percentage of HES1-positive cells among Notch2-positive cells was less than half that of the control. The present results suggest that E-cadherin-mediated cell attachment is necessary for the activation of Notch signaling in the anterior pituitary gland but not for the expression of the Notch2 molecule.

  15. Inhibitory effects of Melatonin on the proliferation of 17-β-estrogen-induced pituitary prolactin-secreting tumor cells in rats%褪黑激素对17-β-雌二醇诱致的大鼠垂体催乳素瘤细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    高列; 单惠敏; 许荣焜; 许建萍

    2001-01-01

    In present study,we have examined the effect of melatonin at different concentrations on the proliferation of 17-β-estrogen(E2)-induced prolactinoma cells of rats.The prolactinomas were established by implanting E2-laden silastic capsule subcutaneously in 80~100 g weight Sprague-Dawley (SD) male rats.Ninety days after E2 capsules implantation,the animals were killed,and prolactinomas were removed.The suspension of tumor cells was obtained by enzymatic digestion,filtration,centrifugation,and resuspension in incubating medium.1 ml aliquot of the cell suspension containing 0.75×106 cells were distributed into each well of 24 well cell culture plate respectively.Then MLT was added to appropriate wells to make the final concentration 10-5 to 10-13 mol/L.Respective quantity of ethanol was added to control wells.Then the cells were incubated at 37℃ in 5 % CO2.After 1 h,74KBq(2μCi) / 2 μL of [3H]-TdR was added in 50 μL of the medium.The incubation was terminated 24 h later,and then the radioactivity was counted.The result showed that the radioactivity (counts/min) of [3H]-TdR in tumor cells in control group and test group at doses of 10-5 ,10-7 ,10-9 ,10-11 and 10-13 mol/L melatonin were 2038.75 ±186.84,1421.75 ±64.49,1238.25 ± 61.72,924 ± 64.44,1033.25± 127.22 and 1103.25 ±151.53,respectively.The results suggested that Melatonin in the concentration range 10-5~10-13 mol/L could inhibit the proliferation of 17-β-estrogen-induced rat prolactinoma cells.%观察不同浓度的褪黑激素 (Melatonin, MLT) 对原代培养的大鼠垂体催乳素瘤细胞增殖的影响。用80~100 g体重的雄性Sprague-Dawley(SD)大鼠,皮下埋置雌二醇诱致垂体催乳素瘤(prolactinoma)形成后,取出瘤体,经消化、过滤、离心,用SFFD培养基重悬细胞,得细胞悬液,浓度为0.75×106/mL,转入24孔培养板中并加入相应剂量的MLT使其终浓度 (mol/L) 分别为10-5、 10-7 、10-9、10-11 和 10-13

  16. Laminin in the anterior pituitary gland of the rat. Laminin in the gonadotrophic cells correlates with their functional state

    DEFF Research Database (Denmark)

    Holck, S; Albrechtsen, R; Wewer, U M

    1987-01-01

    The distribution pattern of laminin in the rat anterior pituitary gland under physiological and hormonally altered conditions was studied immunohistochemically. Intense immunoreactivity of the capillaries and of the basement membranes surrounding parenchymal cells was found. Five to 10% of the pa......The distribution pattern of laminin in the rat anterior pituitary gland under physiological and hormonally altered conditions was studied immunohistochemically. Intense immunoreactivity of the capillaries and of the basement membranes surrounding parenchymal cells was found. Five to 10...... laminin and tubulin. After treatment with estrogen, which is known to suppress the function of the gonadotrophic cells, virtually no cytoplasmic laminin was found. Ultrastructurally, the number of light bodies in the gonadotrophic cells diminished significantly, from approximately 3 to 8 per cell to 0...... to 1 per cell in a given section. In contrast, after castration, the number of laminin positive cells increased to a number above that found in the normal adult male rat, and the number of light bodies increased two to four times. Based on these results, it appears that the presence of cytoplasmic...

  17. Management of nonfunctioning islet cell tumors

    Institute of Scientific and Technical Information of China (English)

    Han Liang; Pu Wang; Xiao-Na Wang; Jia-Cang Wang; Xi-Shan Hao

    2004-01-01

    AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years.METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests.RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twentyeight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%),nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients.Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than :10 cm were positive prognostic factors in females younger than 30years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007.CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are

  18. Neutrophil-tumor cell cannibalism in oral squamous cell carcinoma.

    Science.gov (United States)

    Sarode, Sachin C; Sarode, Gargi S

    2014-07-01

    Cannibalism was recognized as a phenomenon seen mainly with the tumor cells ingesting other tumor cells. Recent reports have shown tumor cell engulfing other cells (xeno-cannibalism) as well, such as neutrophils, lymphocytes and erythrocytes. But no such finding has been reported in oral squamous cell carcinoma (OSCC) in the literature till date. Retrospective histopathological analysis of OSCC for identification of neutrophil-tumor cell cannibalism (NTCC) and its correlation with clinico-pathological parameters. The hematoxylin and eosin stained tissue sections of 500 OSCC cases were thoroughly screened at high power magnification (400X) for NTCC. Cases showing only frank NTCC were selected. Cases were subjected to immunohistochemical analysis using CD68 and lysozyme. Seven (1.4%) cases of OSCC which showed classical features of extreme NTCC on histopathological examination. Seventeen Cases (3.4%) showing occasional isolated NTCC were excluded. All the cases were poorly differentiated and showed cervical lymph node metastasis. Immunohistochemical analysis showed mild (+) to moderate (++) positivity in tumor cells for CD68 and lysozyme markers. NTCC in OSCC can predict the biological behavior and could serve as a useful prognostic marker in future. Tumor cell displaying macrophage phenotype and cell digestion could be mediated through lysosomal enzyme activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

    Science.gov (United States)

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

    2015-08-01

    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

  20. Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

    Directory of Open Access Journals (Sweden)

    Huei-Fang Wang

    2007-09-01

    Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

  1. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  2. Cyberknife radiosurgery for cranial plasma cell tumor.

    Science.gov (United States)

    Alafaci, Cetty; Grasso, Giovanni; Conti, Alfredo; Caffo, Mariella; Salpietro, Francesco Maria; Tomasello, Francesco

    2014-01-01

    Cranial and intracranial involvement by myelomatous disease is relatively uncommon. Furthermore, systemic manifestations of multiple myeloma are present in the majority of these cases at the time of symptom onset. The authors report the case of a patient with serial appearance of multiple intracranial plasma cell tumor localizations as the first manifestations of a multiple myeloma. The patient was treated with CyberKnife radiosurgery for a lesion localized at the clivus and sella turcica with complete local control. With such a technique, based on high-dose conformality, the tumor was centered with an ablative dose of radiation and, at the same time, with a low dose spreading to the surrounding critical structures. The radiosensitivity of plasma cell tumors renders this treatment modality particularly advantageous for their localized manifestation. A technical description of this case is provided. To our knowledge, this is the first case of successful Cyberknife radiosurgery of multifocal intracranial plasmacytoma.

  3. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology.

  4. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

    Directory of Open Access Journals (Sweden)

    Shiva Mansouri

    Full Text Available Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP and the glucagon-like peptide-1 receptor (GLP-1R agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia.

  5. Syndecans in tumor cell adhesion and signaling

    Directory of Open Access Journals (Sweden)

    Rapraeger Alan C

    2004-01-01

    Full Text Available Abstract Anchorage of cells to "heparin" – binding domains that are prevalent in extracellular matrix (ECM components is thought to occur primarily through the syndecans, a four-member family of transmembrane heparan sulfate proteoglycans that communicate environmental cues from the ECM to the cytoskeleton and the signaling apparatus of the cell. Known activities of the syndecans trace to their highly conserved cytoplasmic domains and to their heparan sulfate chains, which can serve to regulate the signaling of growth factors and morphogens. However, several emerging studies point to critical roles for the syndecans' extracellular protein domains in tumor cell behavior to include cell adhesion and invasion. Although the mechanisms of these activities remain largely unknown, one possibility involves "co-receptor" interactions with integrins that may regulate integrin function and the cell adhesion-signaling phenotype. Thus, alterations in syndecan expression, leading to either overexpression or loss of expression, both of which take place in tumor cells, may have dramatic effects on tumor cell invasion.

  6. Redefining circulating tumor cells by image processing

    NARCIS (Netherlands)

    Ligthart, Sjoerd

    2012-01-01

    Circulating tumor cells (CTC) in the blood of patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. However, CTC are very heterogeneous in size and shape, and are present at very low frequencies. Missing or misjudging a few events may have great

  7. Multifunctional Nucleic Acids for Tumor Cell Treatment

    DEFF Research Database (Denmark)

    Pofahl, Monika; Wengel, Jesper; Mayer, Günter

    2014-01-01

    -proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor targeting...

  8. Redefining circulating tumor cells by image processing

    NARCIS (Netherlands)

    Ligthart, S.T.

    2012-01-01

    Circulating tumor cells (CTC) in the blood of patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. However, CTC are very heterogeneous in size and shape, and are present at very low frequencies. Missing or misjudging a few events may have great cons

  9. Redefining circulating tumor cells by image processing

    NARCIS (Netherlands)

    Ligthart, Sjoerd

    2012-01-01

    Circulating tumor cells (CTC) in the blood of patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. However, CTC are very heterogeneous in size and shape, and are present at very low frequencies. Missing or misjudging a few events may have great cons

  10. Metabolic Hallmarks of Tumor and Immune Cells in the Tumor Microenvironment

    Science.gov (United States)

    Renner, Kathrin; Singer, Katrin; Koehl, Gudrun E.; Geissler, Edward K.; Peter, Katrin; Siska, Peter J.; Kreutz, Marina

    2017-01-01

    Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response. Immunosuppression in the tumor microenvironment is often based on the mutual metabolic requirements of immune cells and tumor cells. Cytotoxic T and NK cell activation leads to an increased demand for glucose and amino acids, a well-known feature shown by tumor cells. These close metabolic interdependencies result in metabolic competition, limiting the proliferation, and effector functions of tumor-specific immune cells. Moreover, not only nutrient restriction but also tumor-driven shifts in metabolite abundance and accumulation of metabolic waste products (e.g., lactate) lead to local immunosuppression, thereby facilitating tumor progression and metastasis. In this review, we describe the metabolic interplay between immune cells and tumor cells and discuss tumor cell metabolism as a target structure for cancer therapy. Metabolic (re)education of tumor cells is not only an approach to kill tumor cells directly but could overcome metabolic immunosuppression in the tumor microenvironment and thereby facilitate immunotherapy. PMID:28337200

  11. Metabolic Hallmarks of Tumor and Immune Cells in the Tumor Microenvironment.

    Science.gov (United States)

    Renner, Kathrin; Singer, Katrin; Koehl, Gudrun E; Geissler, Edward K; Peter, Katrin; Siska, Peter J; Kreutz, Marina

    2017-01-01

    Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response. Immunosuppression in the tumor microenvironment is often based on the mutual metabolic requirements of immune cells and tumor cells. Cytotoxic T and NK cell activation leads to an increased demand for glucose and amino acids, a well-known feature shown by tumor cells. These close metabolic interdependencies result in metabolic competition, limiting the proliferation, and effector functions of tumor-specific immune cells. Moreover, not only nutrient restriction but also tumor-driven shifts in metabolite abundance and accumulation of metabolic waste products (e.g., lactate) lead to local immunosuppression, thereby facilitating tumor progression and metastasis. In this review, we describe the metabolic interplay between immune cells and tumor cells and discuss tumor cell metabolism as a target structure for cancer therapy. Metabolic (re)education of tumor cells is not only an approach to kill tumor cells directly but could overcome metabolic immunosuppression in the tumor microenvironment and thereby facilitate immunotherapy.

  12. Immunohistochemical study of pituitary cells in wild and captive Salminus hilarii (Characiformes: Characidae) females during the annual reproductive cycle.

    Science.gov (United States)

    Honji, Renato Massaaki; Nóbrega, Rafael Henrique; Pandolfi, Matias; Shimizu, Akio; Borella, Maria Inês; Moreira, Renata Guimarães

    2013-01-01

    Freshwater fish that live exclusively in rivers are at particular risk from fragmentation of the aquatic system, mainly the species that migrate upriver for reproduction. That is the case of Salminus hilarii, an important migratory species currently classified as "almost threatened" in the São Paulo State (Brazil), facing water pollution, dam construction, riparian habitat destruction and environmental changes that are even more serious in this State. Additionally, this species show ovulation dysfunction in captivity. Our studies focused on the identification and distribution of the pituitary cell types in the adenohypophysis of S. hilarii females, including a morphometric analysis that compares pituitary cells from wild and captive broodstocks during the reproductive annual cycle. The morphology of adenohypophysial cells showed differences following the reproductive cycle and the environment. In general, optical density suggested a higher cellular activity during the previtellogenic (growth hormone) and vitellogenic (somatolactin) stages in both environments. Additionally, the nucleus/cell ratio analysis suggested that growth hormone and somatolactin cells were larger in wild than in captive females in most reproductive stages of the annual cycle. In contrast, prolactin hormone showed no variation throughout the reproductive cycle (in both environments). Morphometrical analyses related to reproduction of S. hilarii in different environmental conditions, suggest that somatolactin and growth hormone play an important role in reproduction in teleost and can be responsible for the regulation of associated processes that indirectly affect reproductive status.

  13. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

    OpenAIRE

    Frohman, L A; Szabo, M; Berelowitz, M.; Stachura, M E

    1980-01-01

    Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amount...

  14. Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Chen; Chung-Wei Wu; Wen-Chen Wang; Li-Min Lin; Yuk-Kwan Chen

    2013-01-01

    We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

  15. CCAAT/Enhancer Binding Protein alpha uses distinct domains to prolong pituitary cells in the Growth 1 and DNA Synthesis phases of the cell cycle

    Directory of Open Access Journals (Sweden)

    Day Richard N

    2002-03-01

    Full Text Available Abstract Background A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα is a basic/leucine zipper transcription factor that integrates transcription with proliferation to regulate the differentiation of tissues involved in energy balance. In the pituitary, C/EBPα regulates the transcription of a key metabolic regulator, growth hormone. Results We examined the consequences of C/EBPα expression on proliferation of the transformed, mouse GHFT1-5 pituitary progenitor cell line. In contrast to mature pituitary cells, GHFT1-5 cells do not contain C/EBPα. Ectopic expression of C/EBPα in the progenitor cells resulted in prolongation of both growth 1 (G1 and the DNA synthesis (S phases of the cell cycle. Transcription activation domain 1 and 2 of C/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as full-length C/EBPα in prolonging G1 and S. Conclusion We found that C/EBPα utilizes mechanistically distinct activities to prolong the cell cycle in G1 and S in pituitary progenitor cells. G1 and S phase prolongation did not require that C/EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation.

  16. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  17. Lung metastasis of benign giant cell tumor: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Bosi, Thiago Carneiro da Cunha; Andrade, Fernando Coelho Goulart de; Turtelli, Celso Montenegro; Ribeiro Junior, Helio Antonio [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: tccbosi@yahoo.com.br; Fatureto, Marcelo Cunha [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Thoracic Surgery; Etchebehere, Renata Margarida [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Pathology

    2008-05-15

    Giant cell tumor is the sixth most frequent primary bone neoplasm, affecting long bone metaphysis, most frequently in young adults. On radiological images, this tumor appears as a lytic, well-defined, eccentric lesion. The authors report a case of benign giant cell tumor in a patient who presented with lung metastases five years after undergoing resection of the primary tumor. (author)

  18. The biology of circulating tumor cells.

    Science.gov (United States)

    Pantel, K; Speicher, M R

    2016-03-10

    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice.

  19. NMR exposure sensitizes tumor cells to apoptosis.

    Science.gov (United States)

    Ghibelli, L; Cerella, C; Cordisco, S; Clavarino, G; Marazzi, S; De Nicola, M; Nuccitelli, S; D'Alessio, M; Magrini, A; Bergamaschi, A; Guerrisi, V; Porfiri, L M

    2006-03-01

    NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3-66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95-102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8-2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies.

  20. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    Science.gov (United States)

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  1. Prothymosin-alpha and Ki-67 expression in pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Iga Wierzbicka-Tutka

    2016-11-01

    Full Text Available Introduction: Prothymosin alpha (PTMA, a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation.Material/Methods: We conducted a retrospective analysis of a group of 27 patients, including 15 females (56% and 12 males (44% with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n and PTMA-cytoplasmic (PTMA-c indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression.Results: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009. We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045 and was higher in the case of gonadotropinomas (p=0.026.Conclusions: The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

  2. Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription.

    OpenAIRE

    Shimon, I; Hüttner, A; Said, J; Spirina, O M; Melmed, S

    1996-01-01

    We have shown previously that human prolactinomas express transforming sequences of the heparin-binding secretory transforming gene (hst) which encodes fibroblast growth factor-4 (FGF-4). To elucidate the role of hst in pituitary tumorigenesis we treated primary rat pituitary and pituitary tumor cell cultures with recombinant FGF-4 and also stably transfected pituitary cell lines with full-length human hst cDNA. Transfectants were screened for hst mRNA expression and FGF-4 production. FGF-4 (...

  3. Granular cell tumors of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Kayani Naila

    2007-03-01

    Full Text Available Abstract Background Granular cell tumors (GCTs are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. Materials and methods We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. Results Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100 and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13, neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin and sarcoma (desmin, vimentin markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. Conclusion We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively.

  4. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  5. Does Royal jelly affect tumor cells?

    Directory of Open Access Journals (Sweden)

    Shirzad Maryam

    2013-04-01

    Full Text Available Introduction: Royal jelly is a substance that appears to be effective on immune system and it appears to be effective on both prevention and growth of cancer cells. In this study, we aimed to carry out a research to investigate the effect of royal jelly on the growth of WEHI-164 fibrosarcoma cell in syngenic Balb/c mice. Methods: In an experimental study, 28 male Balb/c mice were designated into four equal groups. The mice were subcutaneously injected with 5x105 WEHI-164 tumor cells on the day zero in the chest area of the animal. Animals in groups 1 to 4 were orally given 100, 200, 300 mg/kg of royal jelly or vehicle, respectively. In every individual mouse, the tumour size was measured every 2 days from day 5 (days 5, 7, 9, 11, 13, 15 and 17. Data were statistically analyzed using Kruskal-Wallis and Mann Whitney-U tests. Result: Our results showed that the mean size of tumor in case group was significantly smaller than the control group in days 11, 13, 15 and 17 (P<0.05. No metastasis was seen in test and control groups. Conclusion: With emphasize on antitumor effect of royal jelly, it seems that royal jelly has important role in control and regression of fibrosarcoma cells. Since royal jelly showed a delayed effect in control of fibrosarcoma, we suggest that royal jelly be used at least 10 days before tumor inoculation.

  6. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  7. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-04-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

  8. Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

    Science.gov (United States)

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2014-02-01

    In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH.

  9. Pediatric Suprasellar Tumors.

    Science.gov (United States)

    McCrea, Heather J; George, Emilie; Settler, Allison; Schwartz, Theodore H; Greenfield, Jeffrey P

    2016-10-01

    The various childhood suprasellar tumors, while pathologically distinct, present similar clinical and surgical challenges as a result of their common anatomic location. These lesions are in close proximity to or may invade the optic nerve and chiasm, pituitary gland and infundibulum, hypothalamus, and third ventricle, leading to presenting features including visual field loss, impairment in visual acuity, endocrine dysfunction, and hydrocephalus. Though many suprasellar lesions are relatively benign in pathology, treatment may be complicated by high surgical morbidity resulting from damage to the hypothalamic-pituitary axis. Here we review the most frequent pediatric lesions occurring in the suprasellar region: craniopharyngioma, chiasmatic glioma, germ cell tumor, Rathke cleft and arachnoid cysts, pituitary adenoma, and histiocytosis. This review outlines both common presenting features and differentiating aspects of these lesions. It also includes classic radiographic presentations and treatment considerations for each lesion.

  10. Distribution Patterns and Developmental Changes of GnRH and GnRHR-Immunopositive Cells in the Pituitary of Ji Ning Gray Goats

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    Liu Xiao, Wang Shu-Ying, Huang Li-Bo, Hou Yan-Meng and Shi Yun-Zhi

    2014-01-01

    Full Text Available Immunohistochemical Strept Avidin Biotin-Peroxidase Complex (SABC three-step method was used to investigate the distribution patterns and developmental changes of GnRH and GnRHR immunopositive (GnRH-ip and GnRHR-ip cells in the pituitary of Ji Ning Gray goats during 0-180 days of age. The results showed that GnRH-ip and GnRHR-ip cells were detected only in the pars distalis of adenohypophysis. There were no positive cells in the pars intermedia and neurohypophysis. GnRH-ip and GnRHR-ip cells were not observed in the anterior pituitary at birth day and 30 days of age. At 60 days, a number of GnRH-ip and GnRHR-ip cells were found in the anterior pituitary. GnRH-ip cells were pale brown which scattered or clustered around the sinusoid capillary; GnRHR-ip cells were brown and the cytomembrane was darker. The size and percentage of GnRH-ip and GnRHR-ip cells increased with the age growth. The numbers of GnRH-ip and GnRHR-ip cells after sexual maturity were significantly bigger than that before sexual maturity. The results above suggested that GnRH and GnRHR in the pituitary of Ji Ning Gray goats play a pivotal role in the sexual development and sexual maturity.

  11. Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy

    Science.gov (United States)

    2016-12-01

    AD_________________ Award Number: W81XWH-14-1-0350 TITLE: Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy PRINCIPAL...30 Sep 2014 - 29 Sep 2016 4. TITLE AND SUBTILE Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy 5a. CONTRACT NUMBER... cancer . To eradicate chemoresistant tumor cells, it is important to identify the subset of tumor cells that can survive from chemotherapy and

  12. Ectopic Adrenocorticotropic Hormone-Secreting Pituitary Adenomas: An Underestimated Entity.

    Science.gov (United States)

    Knappe, Ulrich J; Jaspers, Christian; Buschsieweke, Desirée; Reinbold, Wolf-Dieter; Alomari, Ali; Saeger, Wolfgang; Ehlenz, Klaus; Mann, W Alexander; Kann, Peter Herbert; Feldkamp, Joachim

    2017-04-01

    The diagnosis of Cushing disease is based on endocrinological pa-rameters, with no single test being specific. In some patients, dynamic thin-slice sellar magnetic resonance imaging fails to detect a pituitary tumor. The purpose of this study is to investigate the role of ectopic pituitary adenoma in this situation. In a retrospective chart review, 5 patients (6%) with ectopic adenomas were identified in 83 consecutive patients undergoing transsphenoidal surgery for adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas by 1 surgeon. In all 5 patients (all female, 32-41 years of age), an exclusively extrasellar ACTH-secreting adenoma was excised. Three adenomas were located in the cavernous sinus, 1 in the sphenoid sinus, and 1 in the ethmoidal cells. Histologically, none of the tumors showed signs of aggressiveness. Three of the 5 adenomas specifically expressed somatostatin receptor 5. In 4 patients with Cushing disease, postoperative remission was obtained, with 1 recurrence after 14 months. In the patient with Nelson syndrome, ACTH decreased from >800 to ectopic adenoma (positive for somatostatin receptor 5) in the ethmoidal cells turned out to be positive on gallium 68 DOTATATE positron emission tomography/computed tomography. The incidence of primarily ectopic ACTH-secreting adenomas in this series was 6%. In cases of negative MRI findings, an ectopic ACTH-secreting adenoma should be taken into account. 68 Ga DOTATATE positron emission tomography/computed tomography may identify ectopic pituitary adenomas. Hypophysectomy should always be avoided in primary surgery for CD.

  13. Stem Cells and the Origin and Propagation of Brain Tumors

    OpenAIRE

    2008-01-01

    In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of “cancer stem cells” that is crucial for tumor maintenance or propagation. While all these concepts are interesting and provide insi...

  14. Multicentric giant cell tumor around the knee

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    Salgia Anil

    2007-01-01

    Full Text Available A case of multicentric giant cell tumor with synchronous occurrence in all three bones around the knee is reported here in view of its rarity. A 33-year-old average built male reported with complaints of severe pain, gradually increasing swelling around the right knee. A 3 x 2 cm swelling was present on the lateral aspect of the distal end of the right femur and a 3 x 3 cm swelling on the proximal part of the right tibia. Plain X-ray of right knee showed subarticular eccentrically located expansile lytic lesion in the lateral tibia condyle, lateral condyle of femur and patella. Fine needle aspiration cytology and subsequent histology ascertained the diagnosis of giant cell tumor of the bone. The patient was treated successfully with curettage, bone grafting and methyl methacrylate cementing (Sandwich technique.

  15. Expression of p53 protein in pituitary adenomas

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    Oliveira M.C.

    2002-01-01

    Full Text Available Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40% male, 60% female. In 35% of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2% of the cases with available neuroimage evaluation, of which 28% invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3%. Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior.

  16. Both pituitary and placental growth hormone transcripts are expressed in human peripheral blood mononuclear cells (PBMC)

    NARCIS (Netherlands)

    Melen, L; Hennen, G; Dullaart, RPF; Igout, A

    1997-01-01

    The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at t

  17. IMAGING IN PITUITARY APOPLEXY

    Directory of Open Access Journals (Sweden)

    Madhukar

    2015-09-01

    Full Text Available Pituitary apoplexy is an acute clinical condition characterized by sudden onset of headache, vomiting, visual disturbance, ophthalmoplegia and altered sensorium occurring due to infarction or haemorrhage of pituitary gland and often involving the pituita ry adenoma. Predominantly seen in non - functional adenomas and in functioning adenomas with prolactinomas having the highest risk. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic i nstability may result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI is performed in suspected cases. On CT, a recent hemorrhage appears as a single or multiple hyperdense lesions with no or little contrast enhancement. MR I is useful in estimating the onset of bleeding and to show the relationship between the tumor and the surrounding structures. CT or MR Angiography is done to rule out aneurysm. Treatment is conservative and surgery is reserved for those cases with deterio rating level of consciousness or increasing visual defect. Here we present a 47 year old male who presented with history of headache and visual disturbances for 6 weeks and was evaluated with radiograph, CT and MRI. A 47 year old male patient presented to the Neurosurgical Department of Vydehi Medical College and Research Centre with history of gradual blurring of vision in the left eye for 2 months. History of diabetes or hypertension was present. The man was hemodynamically stable. Radiograph of the skull showed widening of sella with erosion of the floor. He was advised CT. CT showed widening of sella and a pituitary lesion with fluid level. MRI was advocated for further evaluation. MRI axial and coronal showed sellar and suprasellar mass with figure of e ight appearance mass suggesting pituitary mass. Hyper intense fluid level was seen suggesting bleed within the mass. Contrast MRI showed peripheral enhancement. Diagnosis of

  18. Salivary duct carcinoma with striking neutrophil-tumor cell cannibalism

    OpenAIRE

    Payam Arya; Khalbuss, Walid E.; Monaco, Sara E.; Liron Pantanowitz

    2011-01-01

    Cannibalism of neutrophils by tumor cells has previously been reported in certain carcinomas, lymphoma and melanoma. Tumor cannibalism is believed to serve as a tumor-immune escape mechanism, associated with high-grade aggressive cancers with a significantly increased metastatic potential. This interesting phenomenon has not been previously documented in association with salivary gland tumors. We report, for the first time, striking neutrophil-tumor cell cannibalism associated with a high gra...

  19. Diagnosis and treatment of pituitary adenomas.

    Science.gov (United States)

    Chanson, P; Salenave, S

    2004-12-01

    Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is

  20. Single-cell analyses of circulating tumor cells

    Institute of Scientific and Technical Information of China (English)

    Xi-Xi Chen; Fan Bai

    2015-01-01

    Circulating tumor cells (CTCs) are a population of tumor cells mediating metastasis, which results in most of the cancer related deaths. hTe number of CTCs in the peripheral blood of patients is rare, and many platforms have been launched for detection and enrichment of CTCs. Enumeration of CTCs has already been used as a prognosis marker predicting the survival rate of cancer patients. Yet CTCs should be more potential. Studies on CTCs at single cell level may help revealing the underlying mechanism of tumorigenesis and metastasis. Though far from developed, this area of study holds much promise in providing new clinical application and deep understanding towards metastasis and cancer development.

  1. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  2. Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.

    Science.gov (United States)

    Joshi, Nikhil S; Akama-Garren, Elliot H; Lu, Yisi; Lee, Da-Yae; Chang, Gregory P; Li, Amy; DuPage, Michel; Tammela, Tuomas; Kerper, Natanya R; Farago, Anna F; Robbins, Rebecca; Crowley, Denise M; Bronson, Roderick T; Jacks, Tyler

    2015-09-15

    Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLSs). TA-TLSs have been described in human lung cancers, but their function remains to be determined. TLSs in this model were spatially associated with >90% of tumors and facilitated interactions between T cells and tumor-antigen-presenting dendritic cells (DCs). Costimulatory ligand expression by DCs and T cell proliferation rates increased in TA-TLSs upon Treg cell depletion, leading to tumor destruction. Thus, we propose that Treg cells in TA-TLSs can inhibit endogenous immune responses against tumors, and targeting these cells might provide therapeutic benefit for cancer patients.

  3. A transseptal approach in transsphenoidal surgery for pituitary (hypophyseal) tumors; Dojscie przez przegrode nosowa w operacjach transsfenoidalnych guzow przysadki mozgowej

    Energy Technology Data Exchange (ETDEWEB)

    Gierek, T.; Galuszko-Ignasiak, B.; Krauze, J.; Rudnik, A. [Slaska Akademia Medyczna, Katowice (Poland)]|[Poradnia Otolaryngologiczna dla Dzieci, Zaklad Opieki Zdrowotnej, Swietochlowice (Poland)

    1994-12-31

    The authors described the direct transseptal approach in transsphenoidal surgery for hypophyseal tumors. This route gives a good insight into the area of the sella. The above mentioned method is also less destructive to nasal structures in the nasal cavity, because preserves the anterior nasal septum. It is uniformity of actually views of rhinological school. 20 patients were operated using this method and none of them noticed the changes of nasal airway and the sense of smell. (author)

  4. Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Gulubova M.

    2016-10-01

    Full Text Available The current review reveals the seven subclasses of CD4+ T helper cells, i.e. Th1, Th2, Th9, Th17, Th22, regulatory T cells and Tfh, the cytokines produced by them and their role in tumor microenvironment. Main attention was paid to IL-17 and Th17 cells. IL-17-producing cells were described, among which were Treg17 cells and Tc17 cells. The transcription factors, engaged in the activation of Th17 cell differentiation were reviewed. It was shown that Th17 cells might possess regulatory functions in tumor microenvironments that directs toward immunosuppression. The reciprocity between Treg and Th17 cells is realized when the production of a large amount of TGF-β in tumors causes Treg cell differentiation, and the addition of IL-6 shifts the differentiation of naïve T cells to Th17 cells. The main pro-tumor role of IL-17 is the promotion of tumor angiogenesis through stimulation of fibroblasts and endothelial cells. The antitumor functions of IL-17 are associated with enhancement of cytotoxic activity of tumor specific CTL cells and with angiogenesis that provide channels through which immune cells might invade tumor and promote antitumor immunity.

  5. Photobiomodulation on tumor cells in vitro and tumor tissue in vivo

    Science.gov (United States)

    Rong, Dong-Liang; Liu, Timon Cheng-Yi; Jin, Hua

    2006-01-01

    Background and Objective: There are many kinds of photobiomodulation (PBM) on tumor cells whereas PBM induced oncogenic transformation has not been found. These will be discussed in view of the anti-cancer efficacy of PBM. Study Design/Materials and Methods: The biological information model of PBM (BIMP) will be used to study PBM on tumor cells. Results: The PBM on tumor cells includes cell proliferation, cell cycle modulation, cell adhesion, cell differentiation and so on. The PBM on small tumor tissue in vivo may include the inhibition or promotion of tumor growth. The PBM can be designed to play an important role in anti-cancer treatments in terms of BIMP. Conclusions and discussion: PBM on tumor cells may develop into a novel anti-cancer therapeutic approach.

  6. Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

    NARCIS (Netherlands)

    Ozturk, Cigdem; van Ginkel, Robert J.; Krol, Ruby M.; Gietema, Jourik A.; Hofker, Hendrik S.; Hoekstra, Harald J.

    Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with

  7. Giant cell tumor of the spine.

    Science.gov (United States)

    Ozaki, Toshifumi; Liljenqvist, Ulf; Halm, Henry; Hillmann, Axel; Gosheger, Georg; Winkelmann, Winfried

    2002-08-01

    Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion.

  8. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Catherine Oakman

    2010-06-01

    Full Text Available Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC in the bone marrow and circulating tumor cells (CTC from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer.

  9. Colon tumor cells grown in NASA Bioreactor

    Science.gov (United States)

    2001-01-01

    These photos compare the results of colon carcinoma cells grown in a NASA Bioreactor flown on the STS-70 Space Shuttle in 1995 flight and ground control experiments. The cells grown in microgravity (left) have aggregated to form masses that are larger and more similar to tissue found in the body than the cells cultured on the ground (right). The principal investigator is Milburn Jessup of the University of Texas M. D. Anderson Cancer Center. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Cell constructs grown in a rotating bioreactor on Earth (left) eventually become too large to stay suspended in the nutrient media. In the microgravity of orbit, the cells stay suspended. Rotation then is needed for gentle stirring to replenish the media around the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: NASA and University of Texas M. D. Anderson Cancer Center.

  10. Contribution of mdr1b-type P-glycoprotein to okadaic acid resistance in rat pituitary GH3 cells.

    Science.gov (United States)

    Ritz, V; Marwitz, J; Sieder, S; Ziemann, C; Hirsch-Ernst, K I; Quentin, I; Steinfelder, H J

    1999-08-01

    Okadaic acid as well as other, structurally different, inhibitors of serine/threonine phosphatases 1 and 2A induce apoptosis in pituitary GH3 cells. Incubation with stepwise raised concentrations of okadaic acid resulted in the isolation of cells that were increasingly less sensitive to the cytotoxic effect of this agent. After about 18 months cells were selected that survived at 300 nM okadaic acid, which is about 30 times the initially lethal concentration. This study revealed that a major pharmacokinetic mechanism underlying cell survival was the development of a P-glycoprotein-mediated multidrug resistance (MDR) phenotype. The increase in mRNA levels of the mdr1b P-glycoprotein isoform correlated with the extent of drug resistance. Functional assays revealed that increasing drug resistance was paralleled by a decreased accumulation of rhodamine 123, a fluorescent dye which is a substrate of mdr1-mediated efflux activity. Resistance could be abolished by structurally different chemosensitizers of P-glycoprotein function like verapamil and reserpine but not by the leukotriene receptor antagonist MK571 which is a modulator of the multidrug resistance-associated protein (MRP). Okadaic acid resistance included cross-resistance to other cytotoxic agents that are substrates of mdr1-type P-glycoproteins, like doxorubicin and actinomycin D, but not to non-substrates of mdr1, e.g. cytosine arabinoside. Thus, functional as well as biochemical features support the conclusion that okadaic acid is a substrate of the mdr1-mediated efflux activity in rat pituitary GH3 cells. Maintenance of resistance after withdrawal of okadaic acid as well as metaphase spreads of 100 nM okadaic acid-resistant cells suggested a stable MDR genotype without indications for the occurrence of extrachromosomal amplifications, e.g. double minute chromosomes.

  11. PITUITARY ADENOMA- VISUAL FIELDS, RETINAL NERVE FIBRE LAYER AND GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS ANALYSIS- A CORRELATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Jyoti Shetty

    2017-07-01

    Full Text Available BACKGROUND Pituitary adenoma is a benign and most common tumour of the pituitary gland. It is also the most common parachiasmal tumour and accounts for approximately 10-15% of primary intracranial neoplasms. It has an annual incidence rate of 0.8–8 per 1,00,000 population. Pituitary adenomas are classified as functional and non-functional based on their hormonal activity. Functional adenomas are usually detected earlier due to clinical manifestations produced by excess of hormones. The aim of the study is to analyse visual acuity, visual fields, RNFL thickness and GCIPL thickness on optical coherence tomography (OCT and to find a correlation between these parameters and tumour volume in patients diagnosed with pituitary adenoma. MATERIALS AND METHODS 48 patients diagnosed with pituitary adenoma confirmed by MRI scan underwent complete ophthalmic evaluation (visual acuity, slit-lamp examination, fundus evaluation, perimetry using 30-2 SITA FAST strategy, (Humphrey Field Analyzer; Carl-Zeiss Meditec, Dublin, CA, and OCT of disc (for retinal nerve fibre layer- RNFL thickness and macula (for ganglion cell-inner plexiform layer (GCIPL thickness using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA at Bangalore West Lions Super Speciality Eye Hospital, between June 2014 to June 2016. Various parameters like Mean Deviation (MD, Pattern Standard Deviation (PSD and RNFL and GCIPL thickness on OCT were analysed and correlated with each other. RESULTS Mean tumour volume in patients was 12.26 ± 15.8 cm3 . Most of the patients had visual acuity 6/18 or better. Bitemporal hemianopia was seen in only 5 (12.2% patients. Superotemporal quadrantanopia, arcuate defects, tubular fields and homonymous hemianopia were the other field defects seen. Total and pattern deviation plot of visual fields correlated well with tumour volume and visual acuity. On visual field analysis, the MD (-8.18 ± 8.65 dB was depressed compared to the control group (-2.0 ± 1.8 dB, and

  12. GRANULAR CELL TUMOR OF BREAST (CYTOLOGICAL DIAGNOSIS CONFIRMED BY HISTOPATHOLOGY

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-10-01

    Full Text Available Granular cell tumor is a tumor derived from Schwann cells of peripheral nerves and it can occur throughout the body. About 5% of granular cell tumors occur in breast and are mostly benign in nature. We report a case of 30 year old female who presented with a swelling in right breast which on histo pathological examination revealed features consistent with granular cell tumor. This case is highlighted to reveal the importance of histopathology in differentiating granular cell tumor from carcinoma breast which is difficult based on clinical, radiological and cytological examination alone.

  13. Pituitary magnetic resonance imaging in Cushing's disease.

    Science.gov (United States)

    Vitale, Giovanni; Tortora, Fabio; Baldelli, Roberto; Cocchiara, Francesco; Paragliola, Rosa Maria; Sbardella, Emilia; Simeoli, Chiara; Caranci, Ferdinando; Pivonello, Rosario; Colao, Annamaria

    2017-03-01

    Adrenocorticotropin-secreting pituitary tumor represents about 10 % of pituitary adenomas and at the time of diagnosis most of them are microadenomas. Transsphenoidal surgery is the first-line treatment of Cushing's disease and accurate localization of the tumor within the gland is essential for selectively removing the lesion and preserving normal pituitary function. Magnetic resonance imaging is the best imaging modality for the detection of pituitary tumors, but adrenocorticotropin-secreting pituitary microadenomas are not correctly identified in 30-50 % of cases, because of their size, location, and enhancing characteristics. Several recent studies were performed with the purpose of better localizing the adrenocorticotropin-secreting microadenomas through the use in magnetic resonance imaging of specific sequences, reduced contrast medium dose and high-field technology. Therefore, an improved imaging technique for pituitary disease is mandatory in the suspect of Cushing's disease. The aims of this paper are to present an overview of pituitary magnetic resonance imaging in the diagnosis of Cushing's disease and to provide a magnetic resonance imaging protocol to be followed in case of suspicion adrenocorticotropin-secreting pituitary adenoma.

  14. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  15. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    Science.gov (United States)

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

  16. Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis

    Directory of Open Access Journals (Sweden)

    Merajver Sofia D

    2010-08-01

    Full Text Available Abstract Background The metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate (TM is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis. Results We used two in vivo models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both in vivo models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase (LOX activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression. Conclusions Taken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance.

  17. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  18. [Precocious pseudopuberty secondary to granulosa cell tumor].

    Science.gov (United States)

    Fernández, F; Jordán, J; Carmona, M; Oliver, A; Gracia, R; González, M; Peralta, A

    1984-12-01

    A case report of pseudoprecocity secondary to a unilateral ovarian tumor of granulosa cells is presented in a 13 month old female. Clinical manifestations appeared at two months of age as unilateral enlargement of the breast, development of pubic hair and vaginal discharge. Plasma estrogen levels were elevated, whereas there was no response of FSH and LH to LH-RH stimulation. The absence of a palpable abdominal mass and a normal ultrasound examination of the abdomen must be pointed out in our case. The suspected clinical and laboratory diagnosis was later confirmed by surgical abdominal examination and ovarian histopathology study. With the exception of a minimal breast enlargement which persists at two years of age, all other signs of pseudoprecocity have disappeared after the surgical removal of the neoplasm. The importance of surgical abdominal examination must be pointed out as a diagnostic method when clinical and laboratory findings suggest an ovarian tumor inspite of normal abdominal palpation, ultrasound and roentgenology.

  19. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Gascoyne, Peter R. C., E-mail: pgascoyn@mdanderson.org [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)

    2014-03-12

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  20. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Directory of Open Access Journals (Sweden)

    Peter R. C. Gascoyne

    2014-03-01

    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  1. Severe acute tumor lysis syndrome in patients with germ-cell tumors

    Directory of Open Access Journals (Sweden)

    Guilherme Alvarenga Feres

    2008-01-01

    Full Text Available Germ-cell tumors are a high-proliferative type of cancer that may evolve to significant bulky disease. Tumor lysis syndrome is rarely reported in this setting. The reports of three patients with germ-cell tumors who developed severe acute tumor lysis syndrome following the start of their anticancer therapy are presented. All patients developed renal dysfunction and multiorgan failure. Patients with extensive germ-cell tumors should be kept on close clinical and laboratory monitoring. Physicians should be aware of this uncommon but severe complication and consider early admission to the intensive care unit for the institution of measures to prevent acute renal failure.

  2. Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

    Science.gov (United States)

    2016-10-01

    Award Number: W81XWH-13-1-0461 TITLE: Targeting Tumor Oct4 to Deplete Prostate Tumor - and Metastasis-Initiating Cells PRINCIPAL INVESTIGATOR: Daotai...29 2016 4. TITLE AND SUBTILE Targeting Tumor Oct4 to Deplete Prostate Tumor - and Metastasis-Initiating Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER...the c-MYC oncogene. POU5F1B is a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due

  3. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2017-08-15

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  4. Influence of leptin on luteinizing hormone and follicle stimulating hormone secreted from cultured rat anterior pituitary cells

    Institute of Scientific and Technical Information of China (English)

    Yuebing Qiao; Xiuyan Ma; Huixian Cui

    2008-01-01

    BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect of different dosages of leptin on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from in vitro cultured rat anterior pituitary cells. DESIGN: Contrast study based on cells. SETTING: This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS: Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS: Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10-12, 1×10-11, 1×10-9, 1×10-7, and 1×10-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES: Contents of LH and FSH were detected by radioimmunology. RESULTS: Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations (P<0.01). LH release in the leptin (1×10-12, 1×10-11, 1×10-7, and 1×10-6 mol/L) groups was significantly higher than that in the control group (P<0.01). FSH content in the leptin (1×10-11, 1×10-9, and 1×10-7 mol/L) groups was significantly higher than that in the control group (P<0.01). CONCLUSION: Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a dose-dependent manner.

  5. Forkhead Box O1 is present in quiescent pituitary cells during development and is increased in the absence of p27 Kip1.

    Directory of Open Access Journals (Sweden)

    Sreeparna Majumdar

    Full Text Available Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27(Kip1-positive cells at e14.5. In the absence of p27(Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27(Kip1.

  6. Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    M.F. Ribeiro

    1997-01-01

    Full Text Available The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradiol-treated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat-1 week-1 for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-1 was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05. Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats

  7. Transcranial surgery for pituitary adenomas.

    Science.gov (United States)

    Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R

    2005-07-01

    Although the transsphenoidal approach is the preferred approach to the vast majority of pituitary tumors with or without suprasellar extension, the transcranial approach remains a vital part of the neurosurgical armamentarium for 1 to 4% of these tumors. The transcranial approach is effective when resection becomes necessary for a portion of a pituitary macroadenoma that is judged to be inaccessible from the transsphenoidal route because of isolation by a narrow waist at the diaphragma sellae, containment within the cavernous sinus lateral to the carotid artery, projection anteriorly onto the planum sphenoidale, or projection laterally into the middle fossa. The application of a transcranial approach in these circumstances may still be mitigated by response to prolactin inhibition of prolactinomas, the frequent lack of necessity to remove asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of evidence that sustained chemical cures can be reliably achieved by removal of secretory adenomas (adrenocorticotropic hormone, growth hormone) from the cavernous sinus. Cranial base surgical techniques have refined the surgical approach to pituitary adenomas but have had less effect on actual surgical indications than anticipated. Because application of the transcranial approach to pituitary adenomas is and should be rare in clinical practice, it is useful to standardize the technique to a default mode with which the surgical team is most experienced and, therefore, most comfortable. Our default mode for transcranial pituitary surgery is the frontotemporal-orbitozygomatic approach.

  8. Circulating tumor cells: highlight on practical implications.

    Science.gov (United States)

    Gazzaniga, Paola; Raimondi, Cristina; Gradilone, Angela; Naso, Giuseppe; Cortesi, Enrico; Frati, Luigi

    2012-02-01

    Circulating tumor cells (CTCs) are cells of presumed epithelial origin, whose prognostic and predictive value in metastatic cancer patients has recently been demonstrated. To date, the count of CTCs through the CellSearch® system represents a valid approach for monitoring disease status in patients with metastatic colorectal, breast, and prostate cancer; in these cancer types, a rise in the CTC count at any time during treatment predicts a poor outcome. Nevertheless, the clinical utility of monitoring CTC counts remains controversial, and what to do when CTC counts rise during therapy still remains an unanswered question. In this report, we suggest how to integrate CTC counts with their molecular characterization to better translate biologic information obtained on CTCs into daily clinical practice.

  9. Mixed germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    Pradhan M Pagaro

    2013-01-01

    Full Text Available Germ cell tumors arise in the ovaries and testis and rarely in other tissues. Mixed germ cell tumors are rare. We report two cases of mixed germ cell tumors, one consisting of seminoma and immature teratoma in the testis of a 30-year-old male and second consisting of a yolk sac tumor and immature teratoma in the ovary of a 17-year-old female. Many combinations of mixed germ cell tumors have been reported but very few cases of the above-mentioned combinations have been reported in literature.

  10. Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Bao-qiang; YANG Quan-hui; XU Rong-kun; XU Jian-ning

    2013-01-01

    Background Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats.Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells.This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma.Methods In the in vivo study,mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin-and 17-β-estradiol (E2)-treated male rats.In the in vitro study,prolactinoma cells mitochondria were harvested.Activities of the four mitochondrial respiratory complexes were assayed using fluorometer.ATP production of prolactinoma cells was estimated using bioluminescent methods.Results Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells.Moreover,in both in vivo and in vitro studies,melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells.Conclusions There is a link between mitochondrial function increase and tumorigenesis.Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

  11. [Circulating tumor cells and prostate cancer prognosis].

    Science.gov (United States)

    Capoun, Otakar; Soukup, Viktor; Mikulová, Veronika; Jančíková, Markéta; Honová, Hana; Kološtová, Katarína; Zima, Tomáš; Hanuš, Tomáš

    2014-01-01

    Prostate cancer (PC) is the most common malignant disease in men. Prognosis of patients with metastatic PC is generally unfavourable; however there are significant differences in survival at this stage of the disease. The definition of prognosis is essential for the selection of therapy, respecting an individual risk. In recent years, the association between circulating tumor cells (CTC) detection and response to PC treatment has been widely investigated. Detection of CTC is based on a metastatic process theory and uses well-known tumor-specific antigens on the cell surface. Individual methods assess CTC with different sensitivity and are not yet efficient at the localised PC stage. Only the method of immunomagnetic separation and semi-automatic visualisation (CellSearchTM) has been validated and approved for the use in the PC management. Assessment of the CTC count directly correlates with the prognosis of patients with castration-resistant PC. Change in the CTC count during the therapy also considerably improves risk estimation and represents a marker of overall survival. New methods of CTC cultivation and gene profiling may contribute to individualisation of the treatment similarly to breast cancer. The authors present a review article about theory, methods of detection and clinical use of CTC in castration-resistant PC.

  12. Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

    Directory of Open Access Journals (Sweden)

    Aziz Mahmoudzadeh

    2016-07-01

    Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

  13. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  14. Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies.

    NARCIS (Netherlands)

    Roodink, I.; Verrijp, K.; Raats, J.; Leenders, W.P.J.

    2009-01-01

    BACKGROUND: Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this st

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

    Science.gov (United States)

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

    2017-05-17

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

  16. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology.

  17. A Think Tank of TINK/TANKs: Tumor-Infiltrating/Tumor-Associated Natural Killer Cells in Tumor Progression and Angiogenesis

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M.

    2014-01-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This “polarization” has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as “TINKs”) and tumor-associated NK (altered peripheral NK cells, which here we call “TANKs”) are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology. PMID:25178695

  18. Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.

    Science.gov (United States)

    Castorina, Alessandro; Giunta, Salvatore; Scuderi, Soraya; D'Agata, Velia

    2012-11-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6-48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum starvation.

  19. Influence of catecholamines, prostaglandins and thyroid hormones on growth hormone secretion by chicken pituitary cells in vitro.

    Science.gov (United States)

    Donoghue, D J; Perez, F M; Diamante, B S; Malamed, S; Scanes, C G

    1990-01-01

    In young chickens plasma concentrations of growth hormone (GH) are depressed by prostaglandins (PG) E1 and E2, epinephrine, norepinephrine, alpha 2 and beta agonists or thyroid hormones. A primary culture of chicken adenohypophyseal cells was used to examine the direct effects of these agents at the level of the pituitary as evaluated by GH release in the presence and absence of growth hormone releasing factor (GRF). Following collagenase dispersion and culture (preincubation, 48 hr) cells were exposed (incubation, 2 hr) to test agents, except for thyroid hormones which were added during the preincubation, and incubation period. Growth hormone release was increased (P less than .05) in the presence of PGE1 (10(-8)M by 34%; 10(-7)M by 54%), PGE2 (10(-8)M by 29%; 10(-7)M by 29%), PGF2 alpha (10(-8)M by 28%), and the beta agonist isoproterenol (10(-7)M by 46%). Basal GH release from chicken pituitary cells was not affected by dopamine, norepinephrine, epinephrine, thyroxine (T4), triiodothyronine (T3), or alpha adrenergic agonists. Growth hormone releasing factor stimulated GH release was not affected by the presence of prostaglandins E1, E2 or F2 alpha in the incubation media. However, GRF stimulated GH release was reduced by high doses of catecholamines: dopamine (10(-6)M by 34%), norepinephrine (10(-6)M by 74%), epinephrine (10(-8)M by 47%; 10(-7)M by 41%; 10(-6)M by 89%), and by the alpha 1 adrenergic agonist, phenylephrine (10(-7)M by 52%), the alpha 2 agonist, clonidine (10(-8)M by 34%; 10(-7)M by 83%) and the beta agonist, isoproterenol (10(-7)M by 64%).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  1. Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle and cell survival.

    Science.gov (United States)

    Suzuki, A; Shiraki, K

    2001-04-01

    Cell death and cell cycle progression are two sides of the same coin, and these two different phenomenons are regulated moderately to maintain the cellular homeostasis. Tumor is one of the disease states produced as a result of the disintegrated regulation and is characterized as cells showing an irreversible progression of cell cycle and a resistance to cell death signaling. Several investigations have been performed for the understanding of cell death or cell cycle, and cell death research has remarkably progressed in these 10 years. Caspase is a nomenclature referring to ICE/CED-3 cysteine proteinase family and plays a central role during cell death. Recently, several investigations raised some possible hypotheses that caspase is also involved in cell cycle regulation. In this issue, therefore, we review the molecular basis of cell death and cell cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.

  2. Diagnostic criteria in invasive pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Moldovan Ioana-Maria

    2016-09-01

    Full Text Available Pituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones. Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas. Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”. Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 & p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha, matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene, apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3, the grade 2b tumor with high risk of recurrence

  3. Increase of S-100 protein-positive stellate cells in the anterior pituitary of chronic alcoholic patients with fatty liver or fatty cirrhosis.

    Directory of Open Access Journals (Sweden)

    Ishikawa T

    2003-04-01

    Full Text Available Healthy subjects 40 years old were used as controls in a study of stellate cells (S-100 protein-containing cells, or S-100 cells in subjects with chronic alcoholism and fatty liver or fatty cirrhosis. S-100 cells were sparsely found in the adenohypophysis of control subjects, and these cells sometimes formed small clusters. However, in chro