Science.gov

Sample records for gastrin receptor-expressing tumours

  1. Oestrogen and progesterone receptor expression in subtypes of canine mammary tumours in intact and ovariectomised dogs.

    PubMed

    Mainenti, M; Rasotto, R; Carnier, P; Zappulli, V

    2014-10-01

    The objective of this study was to investigate as a potential prognostic indicator the relationship between histological subtype of canine mammary tumours (CMTs) and oestrogen-α (ORα) and progesterone (PR) receptor expression. Using immunohistochemistry, receptor expression in neoplastic epithelial cells was assessed in 12 different subtypes in 113 CMTs (34 benign, 79 malignant) and 101 surrounding normal tissues. Sixty-eight and 45 CMTs were from intact and ovariectomised bitches, respectively. Histological subtype strongly influenced ORα/PR expression: simple and complex adenomas as well as simple tubular carcinomas exhibited the greatest expression, whereas immunohistochemical labelling for these receptors was weakest in carcinoma and malignant myoepitheliomas, as well as in solid/anaplastic carcinomas and comedocarcinomas. Receptor expression was generally higher in benign relative to malignant neoplasms, and in the latter it was significantly lower in ovariectomised vs. intact bitches. Lymphatic invasion, mitotic index, nodule diameter, and tumour grade were significantly associated with ORα/PR expression. Although not found to be an independent prognostic indicator, tumours from dogs with <10% cells with ORα/PR expression had a poorer prognosis. Lymphatic invasion, the state of the margins of excision, and mitotic index were found to be independent prognostic indicators. Overall, the results suggest that differences in histological subtype and whether or not a bitch has been ovariectomised should be considered when evaluating the significance of ORα and PR expression in CMTs. PMID:24980810

  2. Changes in FABP1 and gastrin receptor expression in the testes of rats that have undergone electrical injury

    PubMed Central

    LI, XUE-FANG; HUANG, QUAN-YONG; LIU, SHUI-PING

    2015-01-01

    Testicular trauma may occur due to accidental electrical injury. The aim of this study was to investigate alterations in the levels of fatty acid-binding protein 1 (FABP1) and gastrin receptor (gastrin R) in the testes following electrical injury. Sprague-Dawley rats were divided into control, fatal electrocution (220 V, 50 Hz, 60 sec) and electrical injury (220 V, 50 Hz, 60 sec) groups (n=8 per group). The animals in the fatal electrocution and electrical injury groups were deeply anesthetized with sodium pentobarbital prior to each treatment, in which the current was delivered via an anode connected to the left foreleg and a cathode to the right hindleg. The rats that survived were subsequently sacrificed by cervical dislocation. Control animals received cervical dislocation alone. Immunohistochemical analysis was performed to evaluate the protein expression of FABP1 and gastrin R in the testes. Sections were evaluated by digital image analysis. The expression levels of FABP1 and gastrin R were significantly increased following electrical injury, supported by an increase in the integrated optical density (IOD) when compared with that in the control group (P<0.05). However, no significant difference was found in FABP1 and gastrin R expression levels between the fatal electrocution and control groups. In summary, the protein expression levels of FABP1 and gastrin R were found to be significantly altered by electrical injury, suggesting that these two proteins may be important in underlying mechanisms of testicular injury during electrical injury. The findings indicate that such alterations would be reflected in abnormal testicular function. PMID:26136952

  3. Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies.

    PubMed

    Behr, Thomas M; Béhé, Martin P

    2002-04-01

    The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs, but also in a high percentage of small-cell lung cancers, stromal ovarian tumors, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the C-terminal CCK-receptor binding tetrapeptide sequence-Trp-Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of the gastrin or cholecystokinin families or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied and optimized in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in preclinical models. Best tumor uptake and tumor to nontumor ratios were obtained with members of the gastrin family, because of their superior selectivity and affinity for the CCK-B receptor subtype. Radiometal-labeled derivates of minigastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and healthy human volunteers. Preclinical therapy experiments in MTC-bearing animals showed significant antitumor efficacy. In a subsequent clinical study, 45 MTC patients with metastatic MTC were investigated; 23 had known and 22 had occult disease. CCK-B receptor scintigraphy was performed with (111)In-diethylenetriamine pentaacetic acid-d-Glu(1)-minigastrin. The normal organ uptake was

  4. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    PubMed

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways. PMID:16953241

  5. PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules

    PubMed Central

    GAROUSI, JAVAD; ANDERSSON, KEN G.; MITRAN, BOGDAN; PICHL, MARIE-LOUISE; STÅHL, STEFAN; ORLOVA, ANNA; LÖFBLOM, JOHN; TOLMACHEV, VLADIMIR

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide 89Zr. The 89Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160±60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, 89Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6±0.5% ID/g and tumour-to-blood ratio of 3.7±0.6 at 24 h after injection. 89Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody 89Zr-DFO-cetuximab at 48 h after injection. EGFR-expressing tumours were clearly visualized by microPET using 89Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 89Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo. PMID:26847636

  6. PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules.

    PubMed

    Garousi, Javad; Andersson, Ken G; Mitran, Bogdan; Pichl, Marie-Louise; Ståhl, Stefan; Orlova, Anna; Löfblom, John; Tolmachev, Vladimir

    2016-04-01

    Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide (89)Zr. The (89)Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160 ± 60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, (89)Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6 ± 0.5% ID/g and tumour-to-blood ratio of 3.7 ± 0.6 at 24 h after injection. (89)Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody (89)Zr-DFO-cetuximab at 48 h after injection. EGFR‑expressing tumours were clearly visualized by microPET using (89)Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 8(9)Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo. PMID:26847636

  7. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2006-12-12

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  8. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, C. A.

    2001-01-01

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  9. Gastrin Receptor-Avid Peptide Conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2005-07-26

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  10. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Sieckman, Gary; Smith, Charles J.; Gali, Hariprasad

    2006-06-13

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  11. Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues.

    PubMed

    Borrego, J F; Huelsmeyer, M K; Pinkerton, M E; Muszynski, J L; Miller, S A K; Kurzman, I D; Vail, D M

    2016-06-01

    We interrogated the neurokinin-1 receptor (NK-1R)/substance P (SP) pathway in canine melanoma tumour tissues and cell lines. NK-1R messenger RNA (mRNA) and protein expression were observed in the majority of tumour tissues. Immunohistochemical assessment of archived tissue sections revealed NK-1R immunoreactivity in 11 of 15 tumours, which may have diagnostic, prognostic and therapeutic utility. However, we were unable to identify a preclinical in vitro cell line or in vivo xenograft model that recapitulates NK-1R mRNA and protein expression documented in primary tumours. While maropitant inhibited proliferation and enhanced apoptosis in cell lines, in the absence of documented NK-1R expression, this may represent off-target effects. Furthermore, maropitant failed to suppress tumour growth in a canine mouse xenograft model derived from a cell line expressing mRNA but not protein. While NK-1R represents a novel target, in the absence of preclinical models, in-species clinical trials will be necessary to investigate the therapeutic potential for antagonists such as maropitant. PMID:24751104

  12. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

    PubMed Central

    GARONA, JUAN; PIFANO, MARINA; ORLANDO, ULISES D.; PASTRIAN, MARIA B.; IANNUCCI, NANCY B.; ORTEGA, HUGO H.; PODESTA, ERNESTO J.; GOMEZ, DANIEL E.; RIPOLL, GISELLE V.; ALONSO, DANIEL F.

    2015-01-01

    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  13. Gastrin blood test

    MedlinePlus

    ... to an abnormal amount of gastrin. This includes peptic ulcer disease. ... Too much gastrin causes severe peptic ulcer disease. A higher than normal level may also be due to: Chronic kidney disease Long-term gastritis Over-activity of the ...

  14. Gastrin blood test

    MedlinePlus

    ... doctor. Medicines that can increase gastrin measurements include antacids, H 2 -blocking agents (such as cimetidine), and ... Helicobacter pylori infection of the stomach Use of antacids or medicines to treat heartburn Zollinger-Ellison syndrome , ...

  15. Gastrin: The Test

    MedlinePlus

    ... services. Advertising & Sponsorship: Policy | Opportunities PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless you enable Javascript , your ability to navigate and access the features of this website will be ... Share this page: Was this page helpful? Formal name: Gastrin Related tests: Helicobacter pylori , Gastric Acid At a Glance Test ...

  16. Detection of gastrin mRNA in fresh human colonic carcinomas by reverse transcription-polymerase chain reaction.

    PubMed

    Monges, G; Biagini, P; Cantaloube, J F; Chicheportiche, C; Frances, V; Brandini, D; Parc, P; Seitz, J F; Giovannini, M; Sauvan, R

    1993-10-01

    To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present. RNA was extracted from surgical specimens by ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron. These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism. PMID:7507679

  17. Heptadecapeptide gastrin in the vagal nerve.

    PubMed Central

    Uvnäs-Wallensten, K; Rehfeld, J F; Larsson, L I; Uvnäs, B

    1977-01-01

    Immunoreactive gastrin was present in vagal nerves from cats, dogs, and human beings. The abdominal portion of the vagus contained gastrin in amounts ranging from 16 to 273 pmol/g of nerve tissue (wet weight). The thoracic and cervical portion of the vagi contained only minute amounts of gastrin. Gel chromatography of extracts of human, canine, and feline abdominal vagi monitored by region-specific antisera against heptadecapeptide gastrin and triacontatriapeptide cholecystokinin revealed that the vagal gastrin immunoreactivity predominantly consisted of heptadecapeptide gastrin. In addition, the vagi contained small amounts of the NH2-terminal tridecapeptide gastrin fragment as well as of the putative biosynthetic gastrin precursors, components I and II. No cholecystokinin-like molecules were demonstrable. Immunocytochemical studies demonstrated gastrin-containing nerves in the intestinal wall. The nerves were found to be most numerous in the large and distal small intestine. These findings suggest that heptadecapeptide gastrin may represent a new vagal neurotransmitter. Images PMID:23537

  18. Effects of Ostertagia ostertagi on gastrin gene expression and gastrin-related responses in the calf.

    PubMed Central

    Purewal, A; Fox, M T; Shivalkar, P; Carroll, A P; Uche, U E; Vaillant, C; Watkinson, A

    1997-01-01

    1. Infection with the bovine abomasal nematode Ostertagia ostertagi results in a loss of acid-secreting parietal cells and an increase in gastric pH. The effects of an experimental infection on gastrin mRNA expression, blood and tissue gastrin concentrations, the different molecular forms of gastrin in each, and pyloric mucosal chromogranin A-derived peptides were investigated in the calf. 2. An increase in blood gastrin concentrations in the infected group reached a peak by day 28 postinfection (635 pg ml-1; P < 0.01). Gel chromatography analysis of blood samples revealed that the hypergastrinaemia comprised largely gastrin-34 (G-34) in parasitized calves while gastrin-17 (G-17) predominated in control animals. 3. An 11-fold increase in gastrin mRNA expression was recorded in the parasitized animals which was accompanied by a 23.8% reduction in pyloric mucosal gastrin content and an apparent drop of 24.7% in the number of gastrin-producing G cells detected. There was no major change in the relative abundance of G-17 and G-34 in the pyloric mucosa of infected calves. No significant differences in the concentration of pyloric mucosal chromogranin A-derived peptides were recorded between infected and control groups. 4. These data suggest that the hypergastrinaemia seen in parasitized calves results largely from an increase in gastrin synthesis and that depletion of previously stored peptide makes virtually no contribution to elevated blood gastrin concentrations. PMID:9051591

  19. Effect of secretin on release of heterogeneous forms of gastrin.

    PubMed Central

    Straus, E; Greenstein, A J; Yalow, R S

    1975-01-01

    The effect of an intravenous injection of secretin on plasma gastrin concentration is shown to be dependent upon the relative concentration of the major forms of immunoreactive gastrin present in the plasma at the time of injection. Secretin suppressed gastrin secretion in the fasting state in patients in whose plasma heptadecapeptide and big gastrins predominated and did not suppress when big big gastrin comprised more than 90% of plasma gastrin immunoreactivity. The post-secretin decrease in plasma gastrin was due entirely to the disappearance of the smaller, more rapidly degraded forms. Food-stimulated gastrin response was suppressed by secretin for the initial 40 minutes after a test meal but was greater than usual from 40 to 120 minutes. PMID:1218824

  20. Effects of chemotherapy agents on Sphingosine-1-Phosphate receptors expression in MCF-7 mammary cancer cells.

    PubMed

    Ghosal, P; Sukocheva, O A; Wang, T; Mayne, G C; Watson, D I; Hussey, D J

    2016-07-01

    Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in the regulation of cell proliferation and cancer progression. Increased expression of S1P receptors has been detected in advanced breast tumours with poor prognosis suggesting that S1P receptors might control tumour response to chemotherapy. However, it remains unclear how the levels of S1P receptor expression are influenced by chemotherapy agents. Western immunoblotting, PCR analysis and fluorescent microscopy techniques were used in this study to analyze expression patterns of S1P receptors 2 and 3 (S1P2/S1P3) in MCF-7 breast adenocarcinoma cells treated by Tamoxifen (TAM) and/or Medroxyprogesterone acetate (MPA). We found that TAM/MPA induce downregulation of S1P3 receptors, but stimulate expression of S1P2. According to cell viability and caspase activity analyses, as expected, TAM activated apoptosis. We also detected TAM/MPA-induced autophagy marked by formation of macroautophagosomes and increased level of Beclin 1. Combined application of TAM and MPA resulted in synergistic apoptosis- and autophagy-stimulating effects. Assessed by fluorescent microscopy with autophagosome marker LAMP-2, changes in S1P receptor expression coincided with activation of autophagy, suggestively, directing breast cancer cells towards death. Further studies are warranted to explore the utility of manipulation of S1P2 and S1P3 receptor expression as a novel treatment approach. PMID:27261597

  1. The half-life of exogenous gastrin in the circulation

    PubMed Central

    Blair, E. L.; Farra, Yvonne; Richardson, Diana D.; Steinbok, P.

    1970-01-01

    1. A method of gastrin bio-assay is described which can be used on as little as 30 ng synthetic human gastrin I at a minimum concentration of 2·5 ng/ml. 2. Pentagastrin or synthetic human gastrin I added to cat plasma can be stored on ice or at 4° C, for periods up to 27 hr without apparent loss of gastrin activity. 3. Between 1½ and 13 min after the rapid I.V. injection of pentagastrin in the anaesthetized cat and between 1½ and 15 min after the injection of synthetic human gastrin I, there is a rapid reduction of the gastrin concentration in the arterial plasma. The data relating log10 gastrin concentration in arterial plasma with time can be fitted by a single term. 4. Studies in vitro show that over the periods of time involved in the in vivo studies, both pentagastrin and synthetic human gastrin I are stable in cat plasma at 37° C in concentrations which occurred in the circulating plasma. 5. The half-life of pentagastrin in the circulating arterial plasma of the anaesthetized cat is 1·50 min (S.E. ± 0·08) and the half-life of synthetic human gastrin I is 2·65 min (S.E. ± 0·09). ImagesFig. 5 PMID:5500725

  2. Effects of gastrin on calcium homeostasis in chickens

    SciTech Connect

    Persson, P.; Gagnemo-Persson, R.; Orberg, J.; Chen, D.; Hakanson, R. )

    1991-09-01

    As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid-producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. The authors suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa.

  3. Association between Oestrogens Receptor Expressions in Breast Cancer and Comorbidities: A Cross-Sectional, Population-Based Study

    PubMed Central

    de Decker, Laure; Campone, Mario; Retornaz, Frederique; Berrut, Gilles; Kabeshova, Anastasia; Molinié, Florence; Beauchet, Olivier

    2014-01-01

    Background Breast cancer with oestrogen receptor expression is common in older women. Several factors, such as age and reproductive hormone exposure, have been associated with oestrogen receptor expression in breast cancer. However, the association between comorbidities and the oestrogen receptor expression has been poorly studied. We hypothesized that there was an association between burden comorbidity and breast cancer with oestrogen receptor expression in older women. Objective To determine whether oestrogen receptor expression in breast cancer was associated with burden comorbidity in community-dwelling women. Methods A total of 1,707 women with breast cancer registered on the list of a breast cancer registry were included. The recorded data included: age, Charlson Comorbidity Index score≥1, breast cancer characteristics (coded according to the International Classification of Diseases for Oncology), and breast cancer pathological stage (the pathological-tumour-node-metastasis, Scarff Bloom Richardson, and hormonal status of oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor). Results Breast cancer with oestrogen receptor expression was identified in 1,378 patients (80·7%). The fully-adjusted logistic regression showed that oestrogen receptor expression was associated with Charlson Comorbidity Index score≥1 (odds ratio [OR] = 1·91,95%confidence interval [CI] = [1.01–3.61], P = 0·048), progesterone receptor expression (OR = 16·64, 95%CI = [11.62–23.81], P<0·001), human epidermal growth factor receptor (OR = 0·54, 95%CI = [0.34–0.84], P = 0·007), age (OR = 1.02, 95%CI = [1.00–1.03], P = 0.008), Scarff Bloom Richardson grade II and grade III (OR = 0·21with 95%CI = [0.10–0.44] and OR = 0·06 with 95%CI = [0.03–0.12], P<0·001). Conclusion Our findings provide new data showing an independent positive association between burden comorbidity and breast

  4. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1325 Gastrin test system. (a) Identification....

  5. Sinonasal Leiomyoma With Estrogen Receptor Expression.

    PubMed

    Kim, Jong Seung; Shin, Jin Yong; Kwon, Sam Hyun

    2015-09-01

    Leiomyoma is an extremely rare tumor in sinonasal area. The reason for this is due to minimal amount of the smooth muscle in the area. The origin of this tumor is not clear and its etiology has not been proven in the literature. A 58-year-old woman who experienced nasal obstruction and epiphora visited our clinic. A huge mass was noted in right nasal cavity originating from the lacrimal bone area. The authors conducted endoscopic sinus surgery and obtained the specimen. Immunochemistry showed leiomyoma in the nasal cavity, which expressed estrogen receptor. There was no progesterone receptor expressed. The authors describe a sinonasal leiomyoma with estrogen receptors, not ever reported in previous article. PMID:26355987

  6. Autoantibody to the gastrin receptor in pernicious anemia

    SciTech Connect

    de Aizpurua, H.J.; Ungar, B.; Toh, B.H.

    1985-08-22

    The authors examined serum IgG fractions from 20 patients with pernicious anemia and 25 control subjects for their capacity to inhibit binding of (/sup 125/I)15-leu human gastrin-17 to parietal-cell-enriched gastric mucosal cells. IgG fractions from six patients reduced gastrin binding by 45.6 +/- 12.2 per cent, as compared with a reduction of 1.8 +/- 0.7 per cent by fractions from the 25 controls. The fractions from these six patients also reduced gastrin-stimulated (/sup 14/C)aminopyrine uptake by gastric cells (an index of gastric acid secretory activity in vitro) by 50.2 +/- 8.4 per cent (mean +/- S.D.), as compared with 9.2 +/- 4.1 per cent for the controls. IgG fractions from six other patients that did not reduce gastrin binding also inhibited gastrin-stimulated (/sup 14/C)aminopyrine uptake, by 48.1 +/- 9.1 per cent. These reductions in gastrin binding and aminopyrine uptake were abolished by absorption of the IgG fractions with suspensions of viable gastric mucosal cells but not by absorption with liver or kidney cells. The IgG fractions did not inhibit (/sup 3/H)histamine binding or histamine-stimulated (/sup 14/C)aminopyrine uptake. These results suggest that serum IgG from some patients with pernicious anemia contains autoantibodies to the gastrin receptor.

  7. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    NASA Astrophysics Data System (ADS)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  8. Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

    PubMed

    Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

    2016-06-17

    Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. PMID:27179776

  9. Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues.

    PubMed

    Millanta, F; Calandrella, M; Bari, G; Niccolini, M; Vannozzi, I; Poli, A

    2005-12-01

    Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours. PMID:16054892

  10. Regulation of peptide YY homeostasis by gastric acid and gastrin.

    PubMed

    Gomez, G; Padilla, L; Udupi, V; Tarasova, N; Sundler, F; Townsend, C M; Thompson, J C; Greeley, G H

    1996-04-01

    Peptide YY (PYY) is a gut hormone localized primarily in the distal bowel. Because circulating PYY inhibits gastric acid secretion, we investigated the effects of gastric acid secretion and gastrin on gene expression and secretion of PYY. In conscious dogs, PYY release in response to oral food was inhibited (P < 0.05) by pharmacologic inhibition of gastric acid secretion (omeprazole, famotidine). In rats, omeprazole treatment resulted in a significant elevation in serum gastrin concentrations and a simultaneous decrease in PYY messenger RNA (mRNA) and peptide levels in the colon; administration of a gastrin receptor antagonist (L365, 260) prevented the inhibitory actions of omeprazole on colonic PYY mRNA levels. In athymic-nude mice, implantation of a human gastrinoma resulted in an elevation of serum gastrin concentrations and a concomitant depression of colonic PYY mRNA levels. We conclude that endogenous gastric acid secretion up-regulates PYY release and PYY mRNA expression. Circulating gastrin acts to down-regulate PYY release and PYY mRNA expression. This study provides evidence that foregut functions (i.e., gastric acid secretion and gastrin release) exert control over an antiacid signal (e.g. PYY release) emanating from the hindgut. PMID:8625912

  11. Cannabinoid-receptor expression in human leukocytes.

    PubMed

    Bouaboula, M; Rinaldi, M; Carayon, P; Carillon, C; Delpech, B; Shire, D; Le Fur, G; Casellas, P

    1993-05-15

    Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery. Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes. The distribution pattern displays important variations of the mRNA level for the cannabinoid receptor among the main human blood cell subpopulations. The rank order of mRNA levels in these cells is B cells > natural killer cells > or = polymorphonuclear neutrophils > or = T8 cells > monocytes > T4 cells. Cannabinoid-receptor mRNA, which is also found in monocytic, as well as T and B leukemia cell lines but not in Jurkat cells, presents a great diversity of expression on these cells as well, B-cell lines expressing a much higher level than T-cell lines. The cannabinoid receptor PCR products from leukocytes and brain are identical both in size and sequence suggesting a strong similarity between central and peripheral cannabinoid receptors. The expression of this receptor was demonstrated on membranes of the myelomonocytic U937 cells using the synthetic cannabinoid [3H]CP-55940 as ligand. The Kd determined from Scatchard analysis was 0.1 nM and the Bmax for membranes was 525 fmol/mg protein. The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells. PMID

  12. Autoantibody against diiodinated tyrosine-gastrin in a patient with Graves' disease

    SciTech Connect

    Noguchi, M.; Adachi, H.; Aoki, E.; Iida, Y.; Kasagi, K.; Endo, K.; Konishi, J.; Torizuka, K.

    1987-01-01

    We describe autoantibodies against iodinated gastrin in a patient with Graves' disease. Values for serum gastrin differed in this case, depending on which of two different radioimmunoassay (RIA) kits was used. RIA with the dextran-coated charcoal method for separation of free tracer gastrin gave a value less than 9.5 pmol/L, whereas the value by a RIA kit by the double-antibody method was 318 pmol/L. The patient's serum contained a binding protein for /sup 125/I-labeled gastrin, as detected by Sephadex G-200 column chromatography. The IgG fraction was responsible for the ability of serum to bind /sup 125/I-labeled gastrin. Interestingly, of the two possible forms of iodinated gastrins, monoiodinated (MIT) and diiodinated (DIT) tyrosine-/sup 125/I-labeled gastrin, only the latter bound to patient's IgG. Furthermore, DIT-gastrin, but not gastrin or MIT-gastrin, inhibited the binding of DIT-/sup 125/I-labeled gastrin. The patient's serum evidently contains autoantibodies against DIT-gastrin that interfere with RIA of gastrin.

  13. Effect of regular and decaffeinated coffee on serum gastrin levels.

    PubMed

    Acquaviva, F; DeFrancesco, A; Andriulli, A; Piantino, P; Arrigoni, A; Massarenti, P; Balzola, F

    1986-04-01

    We evaluated the hypothesis that the noncaffeine gastric acid stimulant effect of coffee might be by way of serum gastrin release. After 10 healthy volunteers drank 50 ml of coffee solution corresponding to one cup of home-made regular coffee containing 10 g of sugar and 240 mg/100 ml of caffeine, serum total gastrin levels peaked at 10 min and returned to basal values within 30 min; the response was of little significance (1.24 times the median basal value). Drinking 100 ml of sugared water (as control) resulted in occasional random elevations of serum gastrin which were not statistically significant. Drinking 100 ml of regular or decaffeinated coffee resulted in a prompt and lasting elevation of total gastrin; mean integrated outputs after regular or decaffeinated coffee were, respectively, 2.3 and 1.7 times the values in the control test. Regular and decaffeinated coffees share a strong gastrin-releasing property. Neither distension, osmolarity, calcium, nor amino acid content of the coffee solution can account for this property, which should be ascribed to some other unidentified ingredient. This property is at least partially lost during the process of caffeine removal. PMID:3745848

  14. High Affinity Binding of Indium and Ruthenium Ions by Gastrins

    PubMed Central

    Baldwin, Graham S.; George, Graham N.; Pushie, M. Jake

    2015-01-01

    The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd) of 3.3 x 10−7 and 1.1 x 10−6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10−15 and 1.7 x 10−7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10−13 and 1.2 x 10−5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0–3.3 Å, the Ru complex clearly demonstrated a short range Ru—Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy. PMID:26457677

  15. Gastrin release in fistula dogs with solid compared to nutrient and nonnutrient liquid meals.

    PubMed

    Hirschowitz, B I

    1983-08-01

    Using conscious gastric fistula dogs, gastrin release stimulated by a 360-g meat-based solid meal was compared to that stimulated by two isocaloric (1 kcal/g), hypertonic (approximately 700 mosm/kg) nutrient liquids (Sustacal and Vivonex) and by two nonnutrient, hypotonic (60 mosm/kg) liquids (mannitol and coffee). Serum gastrin levels were measured at 15- to 30-min intervals over 120 min. Without a meal, serum gastrin levels remained stable. Effectiveness in stimulating gastrin release was coffee = mannitol less than Sustacal = Vivonex less than solid food; 2-hr integrated gastrin responses were 1.2, 2.6, 4.3, 5.6, and 12.2 ng/ml/min, respectively. The greater gastrin responses produced by nutrient liquids and meat meals could be explained by slower emptying and delayed acidification of gastric contents. We conclude that solid meals are preferable to liquid meals in studies of antral gastrin release. PMID:6409571

  16. Treadmill exercise enhances NMDA receptor expression in schizophrenia mice

    PubMed Central

    Park, Joon-Ki; Lee, Sam-Jun; Kim, Tae-Won

    2014-01-01

    Schizophrenia is a serious psychiatric disorder with several symptoms including cognitive dysfunction. Although the causes of schizophrenia are still unclear, there is a strong suspicion that the abnormality in N-methyl-D-aspartate (NMDA) receptor may contribute to schizophrenia symptoms. In the present study, the effect of treadmill exercise on the NMDA receptor expression was evaluated using MK-801-induced schizophrenia mice. Immunohistochemistry for expressions of NMDA receptor tyrosine hydroxylase (TH) was conducted. Western blot for brain-derived neurotrophic factor (BDNF) was also performed. In the present results, the mice in the MK-801-treated group displayed reduced NMDA receptor expression. Enhanced TH expression and suppressed BDNF expression were also observed in the MK-801-treated mice. Treadmill exercise improved NMDA receptor expression in the MK-801-induced schizophrenia mice. Treadmill exercise also suppressed TH expression and enhanced BDNF expression in the MK-801-induced schizophrenia mice. The present study showed that down-regulation of NMDA receptor demonstrated schizophrenia-like parameters, meanwhile treadmill running improved schizophrenia-related parameters through enhancing NMDA receptor expression. PMID:24678500

  17. Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression.

    PubMed Central

    Liao, W; Rudling, M; Angelin, B

    1996-01-01

    Endotoxin induces hyperlipidaemia in experimental animals. In the current study, we investigated whether endotoxin alters hepatic low-density lipoprotein (LDL) receptor expression in rats. Endotoxin treatment suppressed hepatic LDL receptor expression in a dose- and time-dependent manner. Eighteen hours after intraperitoneal injection of increasing amounts of endotoxin, LDL receptor and its mRNA levels were determined by ligand blot and solution hybridization respectively. LDL receptor expression was inhibited by about 70% at a dose of 500 micrograms/100 g body weight. However, LDL receptor mRNA levels were markedly increased in all endotoxin-treated groups at this time point (by 83-136%; P < 0.001). Time-course experiments showed that LDL receptor expression was already reduced by 48% 4 h after endotoxin injection and was maximally reduced (by 63-65%) between 8 and 18 h. Changes in hepatic LDL receptor mRNA showed a different pattern. By 4 h after endotoxin injection, LDL receptor mRNA had decreased by 78% (P < 0.001). However, by 8 h after endotoxin injection, LDL receptor mRNA had returned to levels similar to controls, and 18 and 24 h after endotoxin injection, they were increased by about 60% (P < 0.05). Separation of plasma lipoproteins by FPLC demonstrated that endotoxin-induced changes in plasma triacylglycerols and cholesterol were due to accumulation of plasma apolipoprotein B-containing lipoproteins among very-low-density lipoprotein, intermediate-density lipoprotein and LDL. It is concluded that endotoxin suppresses hepatic LDL receptor expression in vivo in rats. PMID:8611169

  18. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  19. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  20. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  1. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. Gastrin exerts pleiotropic effects on human melanoma cell biology.

    PubMed

    Mathieu, Véronique; Mijatovic, Tatjana; van Damme, Marc; Kiss, Robert

    2005-10-01

    The effects of gastrin (G17) on the growth and migration factors of four human melanoma cell lines (HT-144, C32, G-361, and SKMEL-28) were investigated. The expression patterns of cholecystokinin (CCK)(A), CCK(B), and CCK(C) gastrin receptors were investigated in these cells and in seven clinical samples by means of reverse transcription polymerase chain reaction. Melanoma cells appear to express mRNA for CCK(C) receptors, but not for CCK(A) or CCK(B) receptors. Although gastrin does not significantly modify the growth characteristics of the cell lines under study, it significantly modifies their cell migration characteristics. These modifications occur at adhesion level by modifying the expression levels of alpha(v) and beta3 integrins, at motility level by modifying the organization of the actin cytoskeleton, and at invasion level by modifying the expression levels of matrix metalloproteinase 14. We recently demonstrated the presence of CCK(B) receptors in mouse endothelial cells involved in glioblastoma neoangiogenesis. Chronic in vivo administration of a selective CCK(B) receptor antagonist to mice bearing xenografts of human C32 melanoma cells significantly decreased levels of neoangiogenesis, resulting in considerable delays in the growth of these C32 xenografts. In conclusion, our study identifies the pleiotropic effects of gastrin on melanoma cell biology. PMID:16242076

  3. G cells and gastrin in chronic alcohol-treated rats.

    PubMed

    Todorović, Vera; Koko, Vesna; Budec, Mirela; Mićić, Mileva; Micev, Marjan; Pavlović, Mirjana; Vignjević, Sanja; Drndarević, Neda; Mitrović, Olivera

    2008-02-01

    Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers. PMID:18249268

  4. Inhibition of bombesin-stimulated acid secretion by immunoneutralization of gastrin in dogs.

    PubMed

    Kovacs, T O; Lloyd, K C; Wong, H; Walsh, J H

    1995-01-01

    Bombesin-like peptides stimulate gastrin release and gastric acid secretion. The increase in gastric acid output is thought to be secondary to gastrin release. A monoclonal antibody (MAb) directed specifically to gastrin (MAb 28.2) was used to study the role of circulating gastrin in the regulation of bombesin-stimulated acid secretion in dogs. Seven conscious, fasted dogs with gastric fistulas received intravenous bombesin infusions in fourfold increasing doses from 200 to 3,200 pmol.kg-1.h-1. Each dose was given for 45 min. On separate days, dogs were pretreated with an intravenous infusion of 7 mg of MAb 28.2 or vehicle (0.1% canine serum albumin). Samples of gastric effluent were collected by gravity drainage through the gastric fistula, and acid output was measured by titration of gastric effluent to pH 7.0, using 0.2 N NaOH. Plasma gastrin concentrations were determined by radioimmunoassay. Bombesin infusion produced dose-dependent increases in plasma gastrin concentrations and gastric acid output. Administration of gastrin MAb 28.2 abolished bombesin-stimulated gastric acid output. Immunoneutralization of circulating gastrin in vivo using a gastrin monoclonal antibody in dogs indicates that the acid stimulatory response to bombesin is mediated by gastrin. PMID:7840208

  5. Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel approach to radionuclide therapy.

    PubMed

    Panigone, S; Nunn, A D

    2006-12-01

    Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides. PMID:17043628

  6. Odor memories regulate olfactory receptor expression in the sensory periphery.

    PubMed

    Claudianos, Charles; Lim, Julianne; Young, Melanie; Yan, Shanzhi; Cristino, Alexandre S; Newcomb, Richard D; Gunasekaran, Nivetha; Reinhard, Judith

    2014-05-01

    Odor learning induces structural and functional modifications throughout the olfactory system, but it is currently unknown whether this plasticity extends to the olfactory receptors (Or) in the sensory periphery. Here, we demonstrate that odor learning induces plasticity in olfactory receptor expression in the honeybee, Apis mellifera. Using quantitative RT-PCR analysis, we show that six putative floral scent receptors were differentially expressed in the bee antennae depending on the scent environment that the bees experienced. Or151, which we characterized using an in vitro cell expression system as a broadly tuned receptor binding floral odorants such as linalool, and Or11, the specific receptor for the queen pheromone 9-oxo-decenoic acid, were significantly down-regulated after honeybees were conditioned with the respective odorants in an olfactory learning paradigm. Electroantennogram recordings showed that the neural response of the antenna was similarly reduced after odor learning. Long-term odor memory was essential for inducing these changes, suggesting that the molecular mechanisms involved in olfactory memory also regulate olfactory receptor expression. Our study demonstrates for the first time that olfactory receptor expression is experience-dependent and modulated by scent conditioning, providing novel insight into how molecular regulation at the periphery contributes to plasticity in the olfactory system. PMID:24628891

  7. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies

    PubMed Central

    Smith, Jill P.; Fonkoua, Lionel K.; Moody, Terry W.

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin - responsive tumors. PMID:26929735

  8. Gastrin secretion before and after gastric bypass surgery for morbid obesity.

    PubMed

    Schrumpf, E; Giercksky, K E; Nygaard, K; Fausa, O

    1981-01-01

    Fasting, meal-stimulated, and insulin-hypoglycemia-stimulated serum gastrin levels were measured before and 3 and 12 months after gastric bypass surgery in nine obese patients. The basal gastrin concentration was unaffected by the operation. After a meal both serum gastrin and blood glucose levels were significantly increased before the operation (p less than 0.002), whereas there was no significant gastrin release in response to food 3 and 12 months after the operation. Insulin hypoglycemia did not elicit any gastrin response either before or after gastric bypass surgery, even though considerable hypoglycemia was obtained. It is concluded that this lack of gastrin release after food and insulin hypoglycemia postoperatively may in part explain the rare development of peptic ulcer in patients after extensive gastric exclusion. PMID:7034160

  9. Discovery of a cholecystokinin-gastrin like signaling system in nematodes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Members of the cholecystokinin/gastrin family of peptides, including the arthropod sulfakinins, and their cognate receptors, play an important role in the regulation of feeding behavior and energy homeostasis. Despite many efforts following the discovery of CCK/gastrin immunoreactivity in nematodes ...

  10. Expression and localization of gastrin messenger RNA and peptide in spermatogenic cells.

    PubMed Central

    Schalling, M; Persson, H; Pelto-Huikko, M; Odum, L; Ekman, P; Gottlieb, C; Hökfelt, T; Rehfeld, J F

    1990-01-01

    In previous studies we have shown that the gene encoding cholecystokinin (CCK) is expressed in spermatogenic cells of several mammalian species. In the present study we show that a gene homologous to the CCK-related hormone, gastrin, is expressed in the human testis. The mRNA hybridizing to a human gastrin cDNA probe in the human testis was of the same size (0.7 kb) as gastrin mRNA in the human antrum. By in situ hybridization the gastrinlike mRNA was localized to seminiferous tubules. Immunocytochemical staining of human testis revealed gastrinlike peptides in the seminiferous tubules primarily at a position corresponding to spermatids and spermatozoa. In ejaculated spermatozoa gastrinlike immunoreactivity was localized to the acrosome. Acrosomal localization could also be shown in spermatids with electron microscopy. Extracts of the human testis contained significant amounts of progastrin, but no bioactive amidated gastrins. In contrast, ejaculated sperm contained mature carboxyamidated gastrin 34 and gastrin 17. The concentration of gastrin in ejaculated human spermatozoa varied considerably between individuals. We suggest that amidated gastrin (in humans) and CCK (in other mammals) are released during the acrosome reaction and that they may be important for fertilization. Images PMID:2117026

  11. Monoamine oxidase: an important intracellular regulator of gastrin release in the rat.

    PubMed

    Dial, E J; Huang, J; Delansorne, R; Lichtenberger, L M

    1986-04-01

    The role of monoamine oxidase (MAO) in the meal-induced or amino acid-induced release of gastrin was investigated. Rats that were pretreated with the nonspecific MAO inhibitor nialamide (200 mg/kg) showed a greater rise in meal-induced serum gastrin than did untreated controls. In vitro experiments demonstrated that gastrin secretion from dispersed antral G cells in response to a stimulatory dose of phenylalanine or methylbenzylamine (10 mM) was markedly enhanced if the cells were treated with nialamide. Studies with the more specific MAO inhibitors clorgyline and deprenyl indicated that antral mucosa contained predominantly type A activity. Inhibition of MAO type A with clorgyline, both in vivo and in vitro, resulted in a greater release of gastrin after stimulation by a meal or phenylalanine. It is concluded that MAO may play an important role in the regulation of gastrin release from the G cell by partially controlling the level of amines within the cell. PMID:3081396

  12. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.

    PubMed

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian

    2015-10-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors. PMID:26169832

  13. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors

    PubMed Central

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F.; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe

    2015-01-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a+ and neurogenin 3-expressing (Ngn3+) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors. PMID:26169832

  14. Action of gastrin in guinea pig oxyntic cells. Studies using quantitative cytochemistry.

    PubMed Central

    Heldsinger, A A; Vinik, A I

    1984-01-01

    The mechanism of action of gastrin was investigated using cytochemical quantitation of hydroxyl ion production (HIP) in guinea pig gastric oxyntic mucosa. The reaction depends upon the trapping of OH ions produced during gastric stimulation and is blocked by the benzimidazole, Hassle 149/94, which inhibits the K+ + H+-ATPase and by acetazolamide, an inhibitor of carbonic anhydrase activity. It is thus a measure of hydroxyl ions produced during stimulation of the oxyntic cell and reflects upon hydrogen ion production. Gastrin (2.5 X 10(-16) -2.5 X 10(-12) M) caused a linear dose-dependent stimulation of HIP in the oxyntic cells. The response was biphasic, with an early peak at 90 s and a secondary rise at 240 s, which persisted for 10 min. Natural human gastrin (sulfated and nonsulfated) and the active COOH-terminal octapeptide fragment of gastrin stimulated HIP, whereas the biologically inert NH2-terminal (1-13) fragment of gastrin had no effect. The activation of oxyntic cell HIP by gastrin was neutralized by an antiserum directed towards the COOH-terminus of gastrin and not by nonimmune serum. Cimetidine (10(-5) M) blocked 25% and atropine (10(-5) M) had no effect on gastrin-stimulated HIP. EGTA (10(-3) M) and LaCl3 (10(-3) M) inhibited the action of gastrin by 67 and 52%, respectively. The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and the naphthalene sulfonamides, W-7 and W-13 (10(-5) M), inhibited gastrin-stimulated HIP by 45.6 38.5, 42.3, and 37.2%, respectively. Higher doses of W-7 and W-13 (10(-4) M) inhibited gastrin-stimulated HIP by 83 and 67%. The Ca2+ ionophore, A23187 (10(-4) M), stimulated HIP. Thus, it appears that gastrin stimulation of HIP is complex. 25% of its action is via a histamine-dependent pathway. 45% of its action is dependent upon extracellular Ca2+. Its action is also in part dependent upon a Ca2+/calmodulin mechanism. PMID:6330172

  15. Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.

    PubMed

    Nguyen, Austin Huy; Koenck, Carleigh; Quirk, Shannon K; Lim, Victoria M; Mitkov, Mario V; Trowbridge, Ryan M; Hunter, William J; Agrawal, Devendra K

    2015-10-01

    The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM-1 (a proinflammatory amplifier) and TREM-2 (an anti-inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semiquantitatively scored. Expression of TREM-1 and TREM-2 was higher in keratinocytes than melanoma tissue (TREM-1: p < 0.01; TREM-2: p < 0.01). Whereas TREM-2 was the dominant isoform expressed in normal keratinocytes, TREM-1 expression predominated in melanoma tissue (TREM-1 to TREM-2 ratio: keratinocytes = 0.78; melanoma = 2.08; p < 0.01). The increased TREM ratio in melanoma tissue could give rise to a proinflammatory and protumor state of the microenvironment. This evidence may be suggestive of a TREM-1/TREM-2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma. PMID:26184544

  16. Antipsychotic treatment modulates glutamate transport and NMDA receptor expression.

    PubMed

    Zink, Mathias; Englisch, Susanne; Schmitt, Andrea

    2014-11-01

    Schizophrenia patients often suffer from treatment-resistant cognitive and negative symptoms, both of which are influenced by glutamate neurotransmission. Innovative therapeutic strategies such as agonists at metabotropic glutamate receptors or glycin reuptake inhibitors try to modulate the brain's glutamate network. Interactions of amino acids with monoamines have been described on several levels, and first- and second-generation antipsychotic agents (FGAs, SGAs) are known to exert modulatory effects on the glutamatergic system. This review summarizes the current knowledge on effects of FGAs and SGAs on glutamate transport and receptor expression derived from pharmacological studies. Such studies serve as a control for molecular findings in schizophrenia brain tissue and are clinically relevant. Moreover, they may validate animal models for psychosis, foster basic research on antipsychotic substances and finally lead to a better understanding of how monoaminergic and amino acid neurotransmissions are intertwined. In the light of these results, important differences dependent on antipsychotic substances, dosage and duration of treatment became obvious. While some post-mortem findings might be confounded with multifold drug effects, others are unlikely to be influenced by antipsychotic treatment and could represent important markers of schizophrenia pathophysiology. In similarity to the convergence of toxic and psychotomimetic effects of dopaminergic, serotonergic and anti-glutamatergic substances, the therapeutic mechanisms of SGAs might merge on a yet to be defined molecular level. In particular, serotonergic effects of SGAs, such as an agonism at 5HT1A receptors, represent important targets for further clinical research. PMID:25214389

  17. Opposite effects of bombesin on insulin and gastrin response to food in humans.

    PubMed Central

    Scarpignato, C; Micali, B

    1986-01-01

    The effect of bombesin on insulin and gastrin response to a standard labelled meal was studied in eight healthy male volunteers. The gastric emptying of solids was simultaneously evaluated. During intravenous infusion of the peptide (5 ng/kg/min) the insulin release after eating was greatly reduced whereas food stimulated gastrin release was significantly enhanced. Both effects of bombesin are likely to be connected with the marked inhibition of gastric emptying induced by the peptide. PMID:3516803

  18. Effect of gastrin on liver regeneration after partial hepatectomy in rats.

    PubMed Central

    Rasmussen, T N; Jørgensen, P E; Almdal, T; Poulsen, S S; Olsen, P S

    1990-01-01

    Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary surgery. We found antrectomy to decrease liver regeneration, whereas fundectomy had no effect. Administration of pentagastrin 300 micrograms/kg sc three times daily for two and four days after partial hepatectomy significantly increased the rate of liver regeneration compared with controls. This study suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated. PMID:2318436

  19. Dopamine receptor expression and function in corticotroph pituitary tumors.

    PubMed

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; Kros, Johan M; De Caro, Maria Laura Del Basso; Arvigo, Marica; Annunziato, Lucio; Lombardi, Gaetano; Colao, Annamaria; Hofland, Leo J; Lamberts, Steven W J

    2004-05-01

    The role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D(2) receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion and the in vivo effect of short-term cabergoline treatment on cortisol secretion. D(2) expression was evaluated by receptor-ligand binding, immunohistochemistry, and RT-PCR. A 50% or more decrease in daily urinary cortisol levels was considered a significant clinical response. At receptor-ligand binding, specific binding of [(125)I]epidepride was found in 80% of cases. At immunohistochemistry, specific D(2) immunostaining was found in 75% of cases. D(2) expression was found in 83.3% of cases (D(2long) in 40%, D(2short) in 20%, and both in 40%) by RT-PCR. Significant in vitro inhibition of ACTH secretion was found in 100% of D(2)-positive cases, but not in 100% of D(2)-negative cases by either bromocriptine or cabergoline. A significant in vivo inhibition of cortisol secretion after 3-month cabergoline treatment was found in 60%, although a normalization of cortisol secretion was found in 40% of cases. All cabergoline-responsive cases were associated with D(2) expression, whereas all noncabergoline-responsive cases but one were not associated with D(2) expression. In conclusion, functional D(2) receptors were expressed in approximately 80% of corticotroph pituitary tumors. The effectiveness of cabergoline in normalizing cortisol secretion in 40% of cases supports its therapeutic use in the management of Cushing's disease. PMID:15126577

  20. Repertoire of Chemokine Receptor Expression in the Female Genital Tract

    PubMed Central

    Patterson, Bruce K.; Landay, Alan; Andersson, Jan; Brown, Clark; Behbahani, Homira; Jiyamapa, Dan; Burki, Zareefa; Stanislawski, Donna; Czerniewski, Mary Ann; Garcia, Patricia

    1998-01-01

    Sexually transmitted diseases, genital ulcer disease, and progesterone therapy increase susceptibility to lentivirus transmission. Infection of cells by human immunodeficiency virus (HIV) is dependent on expression of specific chemokine receptors known to function as HIV co-receptors. Quantitative kinetic reverse transcription-polymerase chain reaction was developed to determine the in vivo expression levels of CCR5, CXCR4, CCR3, CCR2b, and the cytomegalovirus-encoded US28 in peripheral blood mononuclear cells and cervical biopsies from 12 women with and without sexually transmitted diseases, genital ulcer disease, and progesterone-predominant conditions. Our data indicate that CCR5 is the major HIV co-receptor expressed in the female genital tract, and CXCR4 is the predominantly expressed HIV co-receptor in peripheral blood. CCR5 mRNA expression in the ectocervix was 10-fold greater than CXCR4, 20-fold greater than CCR2b, and 100-fold greater than CCR3. In peripheral blood, CXCR4 expression was 1.5-fold greater than CCR5, 10-fold greater than CCR2b, and 15-fold greater than CCR3. US28 was not expressed in cervical tissue despite expression in peripheral blood mononuclear cells from five individuals. CCR5 was significantly increased (p < 0.02) in biopsies from women with sexually transmitted diseases and others who were progesterone predominant. In vitro studies demonstrate that progesterone increases CCR5, CXCR4, and CCR3 expression and decreases CCR2b expression in lymphocytes and monocytes/macrophages. Characterization of chemokine receptors at the tissue level provides important information in identifying host determinants of HIV-1 transmission. PMID:9708808

  1. Flow cytometric monitoring of hormone receptor expression in human solid tumors

    NASA Astrophysics Data System (ADS)

    Krishan, Awtar

    2002-05-01

    Hormone receptor expression in human breast and prostate tumors is of diagnostic and therapeutic importance. With the availability of anti-estrogen, androgen and progesterone antibodies, immunohistochemistry has become a standard tool for determination of receptor expression in human tumor biopsies. However, this method is dependent on examination of a small number of cells under a microscope and the data obtained in most cases is not quantitative. As most of the commercially used anti-hormone antibodies have nuclear specificity, we have developed methods for isolation and antigen unmasking of nuclei from formalin fixed/paraffin embedded archival human tumors. After immunostaining with the antibodies and propidium iodide (for DNA content and cell cycle analysis), nuclei are analyzed by multiparametric laser flow cytometry for hormone receptor expression, DNA content, aneuploidy and cell cycle determination. These multiparametric methods are especially important for retrospective studies seeking to correlate hormone receptor expression with clinical response to anti-hormonal therapy of human breast and prostate tumors.

  2. Chemokine receptor expression by inflammatory T cells in EAE

    PubMed Central

    Mony, Jyothi Thyagabhavan; Khorooshi, Reza; Owens, Trevor

    2014-01-01

    Chemokines direct cellular infiltration to tissues, and their receptors and signaling pathways represent targets for therapy in diseases such as multiple sclerosis (MS). The chemokine CCL20 is expressed in choroid plexus, a site of entry of T cells to the central nervous system (CNS). The CCL20 receptor CCR6 has been reported to be selectively expressed by CD4+ T cells that produce the cytokine IL-17 (Th17 cells). Th17 cells and interferon-gamma (IFNγ)-producing Th1 cells are implicated in induction of MS and its animal model experimental autoimmune encephalomyelitis (EAE). We have assessed whether CCR6 identifies specific inflammatory T cell subsets in EAE. Our approach was to induce EAE, and then examine chemokine receptor expression by cytokine-producing T cells sorted from CNS at peak disease. About 7% of CNS-infiltrating CD4+ T cells produced IFNγ in flow cytometric cytokine assays, whereas less than 1% produced IL-17. About 1% of CD4+ T cells produced both cytokines. CCR6 was expressed by Th1, Th1+17 and by Th17 cells, but not by CD8+ T cells. CD8+ T cells expressed CXCR3, which was also expressed by CD4+ T cells, with no correlation to cytokine profile. Messenger RNA for IFNγ, IL-17A, and the Th1 and Th17-associated transcription factors T-bet and RORγt was detected in both CCR6+ and CXCR3+ CD4+ T cells. IFNγ, but not IL-17A mRNA expression was detected in CD8+ T cells in CNS. CCR6 and CD4 were co-localized in spinal cord infiltrates by double immunofluorescence. Consistent with flow cytometry data some but not all CD4+ T cells expressed CCR6 within infiltrates. CD4-negative CCR6+ cells included macrophage/microglial cells. Thus we have for the first time directly studied CD4+ and CD8+ T cells in the CNS of mice with peak EAE, and determined IFNγ and IL17 expression by cells expressing CCR6 and CXCR3. We show that neither CCR6 or CXCR3 align with CD4 T cell subsets, and Th1 or mixed Th1+17 predominate in EAE. PMID:25071447

  3. Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case.

    PubMed

    Kanavaros, P; Hoang, C; Le Bodic, M F; Polivka, M; Hautefeuille, P

    1990-07-01

    Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production. PMID:1966880

  4. The duration of gastrin treatment affects global gene expression and molecular responses involved in ER stress and anti-apoptosis

    PubMed Central

    2013-01-01

    Background How cells decipher the duration of an external signal into different transcriptional outcomes is poorly understood. The hormone gastrin can promote a variety of cellular responses including proliferation, differentiation, migration and anti-apoptosis. While gastrin in normal concentrations has important physiological functions in the gastrointestine, prolonged high levels of gastrin (hypergastrinemia) is related to pathophysiological processes. Results We have used genome-wide microarray time series analysis and molecular studies to identify genes that are affected by the duration of gastrin treatment in adenocarcinoma cells. Among 403 genes differentially regulated in transiently (gastrin removed after 1 h) versus sustained (gastrin present for 14 h) treated cells, 259 genes upregulated by sustained gastrin treatment compared to untreated controls were expressed at lower levels in the transient mode. The difference was subtle for early genes like Junb and c-Fos, but substantial for delayed and late genes. Inhibition of protein synthesis by cycloheximide was used to distinguish between primary and secondary gastrin regulated genes. The majority of gastrin upregulated genes lower expressed in transiently treated cells were primary genes induced independently of de novo protein synthesis. This indicates that the duration effect of gastrin treatment is mainly mediated via post-translational signalling events, while a smaller fraction of the differentially expressed genes are regulated downstream of primary transcriptional events. Indeed, sustained gastrin treatment specifically induced prolonged ERK1/2 activation and elevated levels of the AP-1 subunit protein JUNB. Enrichment analyses of the differentially expressed genes suggested that endoplasmic reticulum (ER) stress and survival is affected by the duration of gastrin treatment. Sustained treatment exerted an anti-apoptotic effect on serum starvation-induced apoptosis via a PKC-dependent mechanism. In

  5. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    PubMed

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510. PMID:26535461

  6. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis

    PubMed Central

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-01-01

    Abstract A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG). An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs). Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45–0.51) and 0.79 (95% CI: 0.77–0.81), respectively. The DOR was 5.93 (95% CI: 2.93–11.99), and the AUC was 0.82. G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future. PMID:27149493

  7. The role of oestrogen and progesterone receptors in breast cancer – immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women

    PubMed Central

    Patera, Janusz; Sobol, Maria; Przybylski, Jacek

    2015-01-01

    Aim of the study Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status. Material and methods Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. Results Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (–) tumours. Conclusions Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics. PMID:26557763

  8. Basal and postprandial serum levels of gastrin in normotensive and hypertensive adults.

    PubMed

    Jiang, Xiaoliang; Wang, Wenjie; Ning, Bin; Liu, Xing; Gong, Jian; Gan, Fusheng; Gao, Xuezhong; Zhang, Lianfeng; Jose, Pedro A; Qin, Chuan; Yang, Zhiwei

    2013-01-01

    Gastrin is a peptide hormone, which acts not only to regulate gastric acid secretion, but also to exert physiological actions such as the regulation of sodium balance. From a case (n = 95)-control (n = 82) study in Fuyang People's Hospital, Anhui Province, China, we found that the fasting serum gastrin levels are similar in normotensive and hypertensive adults but increased to higher levels in the latter group than in the former group after a mixed meal. We suggest that gastrin is involved in the regulation of blood pressure, possibly via the regulation of sodium and water metabolism and/or renin-angiotensin-aldosterone system. However, the mechanism remains to be determined. PMID:22680232

  9. HLA-dependent tumour development: a role for tumour associate macrophages?

    PubMed

    Marchesi, Maddalena; Andersson, Emilia; Villabona, Lisa; Seliger, Barbara; Lundqvist, Andreas; Kiessling, Rolf; Masucci, Giuseppe V

    2013-01-01

    HLA abnormalities on tumour cells for immune escape have been widely described. In addition, cellular components of the tumour microenvironment, in particular myeloid derived suppressor cells (MDSC) and alternatively activated M2 tumour-associated macrophages (TAMs), are involved in tumour promotion, progression, angiogenesis and suppression of anti-tumour immunity. However, the role of HLA in these activities is poorly understood. This review details MHC class I characteristics and describes MHC class I receptors functions. This analysis established the basis for a reflection about the crosstalk among the tumour cells, the TAMs and the cells mediating an immune response.The tumour cells and TAMs exploit MHC class I molecules to modulate the surrounding immune cells. HLA A, B, C and G molecules down-regulate the macrophage myeloid activation through the interaction with the inhibitory LILRB receptors. HLA A, B, C are able to engage inhibitory KIR receptors negatively regulating the Natural Killer and cytotoxic T lymphocytes function while HLA-G induces the secretion of pro-angiogenic cytokines and chemokine thanks to an activator KIR receptor expressed by a minority of peripheral NK cells. The open conformer of classical MHC-I is able to interact with LILRA receptors described as being associated to the Th2-type cytokine response, triggering a condition for the M2 like TAM polarization. In addition, HLA-E antigens on the surface of the TAMs bind the inhibitory receptor CD94/NKG2A expressed by a subset of NK cells and activated cytotoxic T lymphocytes protecting from the cytolysis.Furthermore MHC class II expression by antigen presenting cells is finely regulated by factors provided with immunological capacities. Tumour-associated macrophages show an epigenetically controlled down-regulation of the MHC class II expression induced by the decoy receptor DcR3, a member of the TNFR, which further enhances the M2-like polarization. BAT3, a positive regulator of MHC class

  10. Inhibition of sham feeding-stimulated acid secretion in dogs by immunoneutralization of gastrin.

    PubMed

    Kovacs, T O; Lloyd, K C; Lawson, D C; Pappas, T N; Walsh, J H

    1997-08-01

    A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs. PMID:9277419

  11. Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma

    PubMed Central

    He, Shuang-Wu; Shen, Kang-Qiang; He, Yu-Jun; Xie, Bin; Zhao, Yan-Ming

    1999-01-01

    AIM: To explore the effect and mechanism of gastrin and its an tagonists proglumide and somatostatin on colorectal carcinoma and their clinical significance. METHODS: A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body. The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis, IP3 content was determined by radioimmuno assay, Ca2+ concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 case s of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain. RESULTS: The volume, weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G2M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25 mg/L, the amount of viable cells, IP3 content and Ca2+ concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32 mg/L, they dropped to the lowest level in PG (25 mg/L) + PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3 cm and 6 cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly-differentiated adenocarcinoma group was significantly higher than that of poorly-differentiated and

  12. Accessory Scrotum With Perineal Lipoma: Pathologic Evaluation Including Androgen Receptor Expression

    PubMed Central

    Iida, Keitaro; Mizuno, Kentaro; Nishio, Hidenori; Moritoki, Yoshinobu; Kamisawa, Hideyuki; Kurokawa, Satoshi; Kohri, Kenjiro; Hayashi, Yutaro

    2014-01-01

    Accessory scrotum is an unusual developmental anomaly defined as additional scrotal tissue in addition to a normally developed scrotum. The accessory scrotum arises posterior to the normally located scrotum and does not contain a testis. We report a case of an 18-month-old boy with an accessory scrotum attached to a perineal lipoma. We resected both and determined histologically that they were of the same tissue as the scrotum, including the presence of androgen receptor expression. To the best of our knowledge, this is the first case to assess androgen receptor expression in an accessory scrotum using immunostaining. PMID:26958486

  13. Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET

    PubMed Central

    Stoykow, Christian; Erbes, Thalia; Maecke, Helmut R; Bulla, Stefan; Bartholomä, Mark; Mayer, Sebastian; Drendel, Vanessa; Bronsert, Peter; Werner, Martin; Gitsch, Gerald; Weber, Wolfgang A; Stickeler, Elmar; Meyer, Philipp T

    2016-01-01

    Introduction: The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer. The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist 68Ga-RM2. Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent 68Ga-RM2-PET/CT for pretreatment staging. In vivo tumor uptake of 68Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens. Results: 13/18 tumors demonstrated strongly increased 68Ga-RM2 uptake compared to normal breast tissue (defined as PET-positive). All PET-positive primary tumors were ER- and PR-positive (13/13) in contrast to only 1/5 PET-negative tumors. Mean SUVMAX of ER-positive tumors was 10.6±6.0 compared to 2.3±1.0 in ER-negative tumors (p=0.016). In a multivariate analysis including ER, PR, HER2/neu and MIB-1, only ER expression predicted 68Ga-RM2 uptake (model: r2=0.55, p=0.025). Normal breast tissue showed inter- and intraindividually variable, moderate GRPR binding (SUVMAX 2.3±1.0), while physiological uptake of other organs was considerably less except pancreas. Of note, 68Ga-RM2-PET/CT detected internal mammary lymph nodes with high 68Ga-RM2 uptake (n=8), a contralateral axillary lymph node metastasis (verified by biopsy) and bone metastases (n=1; not detected by bone scan and CT). Conclusion: Our study demonstrates that 68Ga-RM2-PET/CT is a promising imaging method in ER-positive breast cancer. In vivo GRPR binding assessed by 68Ga-RM2-PET/CT correlated with ER expression in primary tumors of untreated patients. PMID:27446498

  14. Presence of CCK-A, B receptors and effect of gastrin and cholecystokinin on growth of pancreatobiliary cancer cell lines

    PubMed Central

    Jang, Jin-Young; Kim, Sun-Whe; Ku, Ja-Lok; Park, Yong-Hyun; Park, Jae-Gahb

    2005-01-01

    AIM: To investigate the effects of gastrin and cholecystokinin (CCK) and their specific antagonists on the growth of pancreatic and biliary tract cancer cell lines. METHODS: Five pancreatic and 6 biliary cancer cell lines with 2 control cells were used in this study. Cell proliferation study was done using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test and direct cell count method. Reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization were performed to examine and quantify the expression of hormonal receptors in these cell lines. RESULTS: SNU-308 showed a growth stimulating effect by gastrin-17, as did SNU-478 by both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). Other cell lines did not respond to gastrin or CCK. In RT-PCR, the presence of CCK-A receptor and CCK-B/gastrin receptor mRNA was detected in all biliary and pancreatic cancer cell lines. In slot blot hybridization, compared to the cell lines which did not respond to hormones, those that responded to hormones showed high expression of receptor mRNA. CONCLUSION: Gastrin and CCK exert a trophic action on some of the biliary tract cancers. PMID:15682471

  15. Salt-Inducible Kinase 1 (SIK1) Is Induced by Gastrin and Inhibits Migration of Gastric Adenocarcinoma Cells

    PubMed Central

    Selvik, Linn-Karina M.; Rao, Shalini; Steigedal, Tonje S.; Haltbakk, Ildri; Misund, Kristine; Bruland, Torunn; Prestvik, Wenche S.; Lægreid, Astrid; Thommesen, Liv

    2014-01-01

    Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas. PMID:25384047

  16. Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin mice.

    PubMed

    Ohno, Takashi; Ohtani, Masahiro; Suto, Hiroyuki; Ohta, Makoto; Imamura, Yoshiaki; Matsuda, Hidetaka; Hiramatsu, Katsushi; Nemoto, Tomoyuki; Nakamoto, Yasunari

    2016-06-01

    Green tea catechins (GTCs) have been implicated in various physiological effects, including anti-carcinogenic activities. In the present study, we evaluated the effects of GTCs specifically on the development of gastritis and pre-malignant lesions in insulin-gastrin mice. Nine-week-old male INS-GAS mice (n=38) were supplemented with GTCs for 4 and 28 weeks, and their body weights, serum gastrin levels, histopathology and pro-inflammatory cytokine levels in gastric tissue and mucosal cell proliferation were monitored. Body weights of the GTC-treated mice were significantly lower than those of the untreated controls (P≤0.05). Serum gastrin levels were suppressed at the age of 37-weeks (P≤0.05). The histopathological scores indicated that the extent of dysplasia was significantly diminished (P≤0.05), although GTC supplementation did not affect the inflammation scores. The messenger RNA levels of interferon (IFN)-γ were significantly reduced at the age of 13 weeks (P≤0.05), although the changes did not reach statistical significance at the age of 37 weeks (P=0.056). The labeling index of Ki-67 immunohistochemistry was significantly decreased (P≤0.05). These results demonstrated that GTCs may play a protective role in the development of gastritis and pre-malignant lesions via an IFN-γ, gastrin, and mucosal cell proliferation-dependent mechanism in this rodent model and potentially in humans. PMID:27035882

  17. Effects of ethanol and nicotine on gastrin and somatostatin release in rats.

    PubMed

    Cho, C H; Ogle, C W; Wong, S H; Lam, S K

    1987-01-01

    An intravenous bolus injection of nicotine (1 mg/kg) markedly elevated gastric acid secretion; oral administration of ethanol (40%, 10 ml/kg) significantly increased arterial serum gastrin and somatostatin levels. Chronic pretreatment with oral nicotine (5 or 25 micrograms/ml in drinking tap water, for 10 days), but not acute pretreatment with a single oral dose of nicotine (2 or 4 mg/kg), inhibited the nicotine-induced gastric acid secretion and ethanol-induced gastrin and somatostatin release. Pretreatment subcutaneously with a ganglion-blocking dose of hexamethonium (10 mg/kg), however, inhibited nicotine-stimulated acid output and ethanol-evoked somatostatin secretion but not ethanol-induced gastrin release. It is concluded that ethanol-evoked gastrin secretion could be due to activation of specific sites which are not nicotinic receptors, but which are depressed by chronic nicotine pretreatment. On the other hand, the release of somatostatin by ethanol appears to be controlled by ganglionic receptors in the gut. PMID:2883103

  18. Activation of the calcium sensing receptor with cinacalcet increases serum gastrin levels in healthy older subjects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastric acidity is postulated to enhance calcium absorption since calcium is better dissolved at low pH. Extracellular calcium stimulates gastrin and gastric acid secretion in humans. Ex vivo studies indicate that the calcium sensing receptor (CaR), which is expressed on the surface of human G cells...

  19. A specific gastrin receptor on plasma membranes of antral smooth muscle.

    PubMed

    Baur, S; Bacon, V C

    1976-12-20

    Plasma membranes with a 17 fold enrichment in 5'-nucleotidase over homogenate were prepared from antral smooth muscle. A specific gastrin receptor on the plasma membranes has been demonstrated. By Scatchard analysis receptor has a Kaff of 2x10(9)M(-1) and a binding capacity of 5x10(-14) moles/mg of membrane protein. PMID:15625862

  20. Evolutionary conservation of the cholecystokinin/gastrin signaling system in nematodes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Members of the cholecystokinin/gastrin family of peptides, including the arthropod sulfakinins, and their cognate receptors, play an important role in the regulation of feeding behavior and energy homeostasis. By using the potential C. elegans CCK receptors as bait, we have isolated and identified ...

  1. Skeletal effects of a gastrin receptor antagonist in H+/K+ATPase beta subunit KO mice.

    PubMed

    Aasarød, Kristin M; Ramezanzadehkoldeh, Masoud; Shabestari, Maziar; Mosti, Mats P; Stunes, Astrid K; Reseland, Janne E; Beisvag, Vidar; Eriksen, Erik Fink; Sandvik, Arne K; Erben, Reinhold G; Schüler, Christiane; Boyce, Malcolm; Skallerud, Bjørn H; Syversen, Unni; Fossmark, Reidar

    2016-08-01

    Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin. In this study, we wanted to examine whether inhibition of the gastrin/CCK2 receptor influences bone quality in these mice. KO and WT mice were given either the gastrin/CCK2 receptor antagonist netazepide dissolved in polyethylene glycol (PEG) or only PEG for 1year. We found significantly lower bone mineral content and BMD, as well as inferior bone microarchitecture in KO mice compared with WT. Biomechanical properties by three-point bending test also proved inferior in KO mice. KO mice receiving netazepide exhibited significantly higher cortical thickness, cortical area fraction, trabecular thickness and trabecular BMD by micro-CT compared with the control group. Three-point bending test also showed higher Young's modulus of elasticity in the netazepide KO group compared with control mice. In conclusion, we observed that the gastrin receptor antagonist netazepide slightly improved bone quality in this mouse model, suggesting that hypergastrinemia may contribute to deteriorated bone quality during acid inhibition. PMID:27325243

  2. Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases

    PubMed Central

    Berna, Marc J.; Jensen, Robert T.

    2009-01-01

    In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. Even though cholecystokinin (CCK) and gastrin were among the first gastrointestinal hormones discovered [1,2], both their physiological roles as well as their roles in clinically relevant gastrointestinal diseases remain unclear and even controversial in many cases [3–6]. The structural characterization of CCK and gastrin [7,8], pharmacological identification [9–13] and cloning [14,15] of CCK and gastrin receptors (CCK1R, CCK2R), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor/agonist knockout animals [16–21] have led to important advancements in our understanding of the physiological and pathophysiological role of CCK and gastrin signaling [3]. Most of these topics

  3. Changes in gastrin and serum pepsinogens in monitoring of Helicobacter pylori response to therapy.

    PubMed

    Pérez-Paramo, M; Albillos, A; Calleja, J L; Salas, C; Marín, M C; Marcos, M L; Cacho, G; Escartín, P; Ortiz-Berrocal, J

    1997-08-01

    The aims of this study in 50 patients with H. pylori infection and duodenal ulcer were to examine the effect of eradication therapy on the serum levels of gastrin, pepsinogen I, and pepsinogen II and to investigate whether monitoring of the serum changes in these peptides after treatment could predict patient outcome. H. pylori status was assessed at entry and one and six months after therapy by culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath test. Significant decreases were observed in the serum levels of gastrin (-11.4 +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45 patients whose infection was eradicated, but not in the patients without eradication. Serum values of these peptides were unchanged in an additional group of 10 patients that only received omeprazol, none of whom had H. pylori eradicated. The best cutoff point of the percentage of each peptide to predict patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II. A pepsinogen II decrease > 15% resulted in the best marker of H. pylori clearance, accurately identifying patient outcome 86.6% of the time, whereas the diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%, respectively. Significant correlations were found between the bacterial load assessed by histology with the serum concentrations of pepsinogen I and II and with the urease activity as measured by the amount of 14CO2 excreted. In conclusion, eradication of H. pylori infection is followed by a significant drop in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the latter are the most uniform and may be used as an indirect tool to predict treatment outcome. PMID:9286242

  4. Epidermal growth factor increases the interaction between nucleolin and heterogeneous nuclear ribonucleoprotein K/poly(C) binding protein 1 complex to regulate the gastrin mRNA turnover.

    PubMed

    Lee, Pin-Tse; Liao, Pao-Chi; Chang, Wen-Chang; Tseng, Joseph T

    2007-12-01

    Gastrin, a gastrointestinal hormone responsible for gastric acid secretion, has been confirmed as a growth factor for gastrointestinal tract malignancies. High expression of gastrin mRNA was observed in pancreatic and colorectal cancer; however, the mechanism is unclear. Epidermal growth factor (EGF) was found to increase gastrin mRNA stability, indicating mRNA turnover regulation mechanism is involved in the control of gastrin mRNA expression. Using biotin-labeled RNA probe pull-down assay combined with mass spectrometry analysis, we identified the heterogeneous nuclear ribonucleoprotein K (hnRNP K) and poly(C) binding protein 1 (PCBP1) bound with the C-rich region in gastrin mRNA 3' untranslated region. Nucleolin bound with the AGCCCU motif and interacted with hnRNP K were also demonstrated. Under EGF treatment, we observed the amount of nucleolin interacting with hnRNP K and gastrin mRNA increased. Using small interfering RNA technology to define their functional roles, we found hnRNP K, PCBP1, and nucleolin were all responsible for stabilizing gastrin mRNA. Moreover, nucleolin plays a crucial role in mediating the increased gastrin mRNA stability induced by EGF signaling. Besides, we also observed hnRNP K/PCBP1 complex bound with the C-rich region in the gastrin mRNA increased nucleolin binding with gastrin mRNA. Finally, a novel binding model was proposed. PMID:17928403

  5. Memory consolidation and amnesia modify 5-HT6 receptors expression in rat brain: an autoradiographic study.

    PubMed

    Meneses, A; Manuel-Apolinar, L; Castillo, C; Castillo, E

    2007-03-12

    Traditionally, the search for memory circuits has been centered on examinations of amnesic and AD patients, cerebral lesions and, neuroimaging. A complementary alternative might be the use of autoradiography with radioligands. Indeed, ex vivo autoradiographic studies offer the advantage to detect functionally active receptors altered by pharmacological tools and memory formation. Hence, herein the 5-HT(6) receptor antagonist SB-399885 and the amnesic drugs scopolamine or dizocilpine were used to manipulate memory consolidation and 5-HT(6) receptors expression was determined by using [(3)H]-SB-258585. Thus, memory consolidation was impaired in scopolamine and dizocilpine treated groups relative to control vehicle but improved it in SB-399885-treated animals. SB-399885 improved memory consolidation seems to be associated with decreased 5-HT(6) receptors expression in 15 out 17 brain areas. Scopolamine or dizocilpine decreased 5-HT(6) receptors expression in nine different brain areas and increased it in CA3 hippocampus or other eight areas, respectively. In brain areas thought to be in charge of procedural memory such basal ganglia (i.e., nucleus accumbens, caudate putamen, and fundus striate) data showed that relative to control animals amnesic groups showed diminished (scopolamine) or augmented (dizocilpine) 5-HT(6) receptor expression. SB-399885 showing improved memory displayed an intermediate expression in these same brain regions. A similar intermediate expression occurs with regard to amygdala, septum, and some cortical areas in charge of explicit memory storage. However, relative to control group amnesic and SB-399885 rats in the hippocampus, region where explicit memory is formed, showed a complex 5-HT(6) receptors expression. In conclusion, these results indicate neural circuits underlying the effects of 5-HT(6) receptor antagonists in autoshaping task and offer some general clues about cognitive processes in general. PMID:17267053

  6. Brain and spinal tumour.

    PubMed

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

    2014-12-01

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

  7. Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

    PubMed

    Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

    2015-07-01

    Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. PMID:26055295

  8. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

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

  9. In Vitro Interleukin-1 and 2 Production and Interleukin 2 Receptor Expression in the Rhesus Monkey

    NASA Technical Reports Server (NTRS)

    Schmitt, Didier A.; Sonnenfeld, Gerald; Husson, David; Tkaczuk, Jean; Andre, Eric; Schaffar, Laurance

    1996-01-01

    Anti-human monoclonal antibodies were used to detect and quantify interleukins-1 and 2 and interleukin-2 receptor expression in peripheral blood mononuclear cells from a rhesus monkey. Interleukin-1 production could be induced by phorbol esters (PMA) and was potentiated by phytohemagglutinin (PHA). Interleukin-2 secretion could also be induced by the combination of PHA and PMA, but only weakly with PHA alone. Interleukin-2 receptor expression was present in a subpopulation of unstimulated lymphocytes and could be enhanced by PHA or PMA. These data show once again that the rhesus monkey immune system is cross-reactive with the human one and that rhesus macaque could be a good model to study interleukin therapy.

  10. Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2014-03-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437

  11. Tumours of the lung

    PubMed Central

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

    1974-01-01

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

  12. NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy.

    PubMed

    Van Acker, Nathalie; Ragé, Michael; Vermeirsch, Hilde; Schrijvers, Dorien; Nuydens, Rony; Byttebier, Geert; Timmers, Maarten; De Schepper, Stefanie; Streffer, Johannes; Andries, Luc; Plaghki, Léon; Cras, Patrick; Meert, Theo

    2016-01-01

    The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes. PMID:27598321

  13. Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice

    PubMed Central

    Chen, Hsing-Jin; Chiang, Bor-Luen

    2015-01-01

    Background Preterm newborns that receive oxygen therapy often develop bronchopulmonary dysplasia (BPD), which is abnormal lung development characterized by impaired alveologenesis. Oxygen-mediated injury is thought to disrupt normal lung growth and development. However, the mechanism of hyperoxia-induced BPD has not been extensively investigated. We established a neonatal mouse model to investigate the effects of normobaric hyperoxia on retinoid metabolism and retinoid receptor expression. Methods Newborn mice were exposed to hyperoxic or normoxic conditions for 15 days. The concentration of retinol and retinyl palmitate in the lung was measured by HPLC to gauge retinoid metabolism. Retinoid receptor mRNA levels were assessed by real-time PCR. Proliferation and retinoid receptor expression in A549 cells were assessed in the presence and absence of exogenous vitamin A. Results Hyperoxia significantly reduced the body and lung weight of neonatal mice. Hyperoxia also downregulated expression of RARα, RARγ, and RXRγ in the lungs of neonatal mice. In vitro, hyperoxia inhibited proliferation and expression of retinoid receptors in A549 cells. Conclusion Hyperoxia disrupted retinoid receptor expression in neonatal mice. PMID:26509921

  14. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

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

  15. Increased gastrin gene expression provides a physiological advantage to mice under hypoxic conditions.

    PubMed

    Laval, Marie; Baldwin, Graham S; Shulkes, Arthur; Marshall, Kathryn M

    2015-01-15

    Hypoxia, or a low concentration of O2, is encountered in humans undertaking activities such as mountain climbing and scuba diving and is important pathophysiologically as a limiting factor in tumor growth. Although data on the interplay between hypoxia and gastrins are limited, gastrin expression is upregulated by hypoxia in gastrointestinal cancer cell lines, and gastrins counterbalance hypoxia by stimulating angiogenesis in vitro and in vivo. The aim of this study was to determine if higher concentrations of the gastrin precursor progastrin are protective against hypoxia in vivo. hGAS mice, which overexpress progastrin in the liver, and mice of the corresponding wild-type FVB/N strain were exposed to normoxia or hypoxia. Iron status was assessed by measurement of serum iron parameters, real-time PCR for mRNAs encoding critical iron regulatory proteins, and Perls' stain and atomic absorption spectrometry for tissue iron concentrations. FVB/N mice lost weight at a faster rate and had higher sickness scores than hGAS mice exposed to hypoxia. Serum iron levels were lower in hGAS than FVB/N mice and decreased further when the animals were exposed to hypoxia. The concentration of iron in the liver was strikingly lower in hGAS than FVB/N mice. We conclude that increased circulating concentrations of progastrin provide a physiological advantage against systemic hypoxia in mice, possibly by increasing the availability of iron stores. This is the first report of an association between progastrin overexpression, hypoxia, and iron homeostasis. PMID:25394662

  16. Expression, purification and characterization of recombinant toxins consisting of truncated gastrin 17 and pseudomonas exotoxin.

    PubMed

    Feng, Xiao-Li; Liu, Xi-Lin; Lu, Shi-Ying; Ren, Hong-Lin; Li, Yan-Song; Hu, Pan; Wang, Quan; Tong, Weihua; Yan, Dong-Ming; Zhou, Yu; Zhang, Song; Jin, Wen; Liu, Zeng-Shan

    2015-01-01

    Gastric cancer is a major cause of mortality and morbidity around world. However the effectiveness of the current approaches to the diagnosis and treatment of gastric cancer is limited. Recombinant targeted toxins may represent a novel direction of cancer therapy. In this study, we aimed to explore whether recombinant toxins fused with the truncated forms of G17 could target to kill cancer cells by recognizing CCK2R. Four recombinant Pseudomonas toxins PE38 fused with the forward or reverse truncated forms of G17 (G14 and G13) were successfully constructed, expressed, and purified. Their characteristics were further analyzed by SDS-PAGE, western blot and indirect immunofluorescence assay. The cytotoxicity assay demonstrated that only reversely fused recombinant toxins rG14PE38 and rG13PE38 exhibited certain toxicity on several cancer cell lines, and a competition assay indicated that the binding of the reverse gastrin-endotoxin to CCK2R (+) cells may be mediated by interaction between gastrin/gastrin-like and CCK2R. PMID:25353354

  17. Lower esophageal sphincter pressure, acid secretion, and blood gastrin after coffee consumption.

    PubMed

    Van Deventer, G; Kamemoto, E; Kuznicki, J T; Heckert, D C; Schulte, M C

    1992-04-01

    This study tested the hypothesis that differences in the processing of raw coffee beans can account for some of the variability in gastric effects of coffee drinking. Coffees were selected to represent several ways that green coffee beans are treated, ie, processing variables. These included instant and ground coffee processing, decaffeination method (ethyl acetate or methylene chloride extraction), instant coffee processing temperature (112 degrees F or 300 degrees F), and steam treatment. Lower esophageal sphincter pressure, acid secretion, and blood gastrin was measured in eight human subjects after they consumed each of the different coffees. Consumption of coffee was followed by a sustained decrease in lower esophageal sphincter pressure (P less than 0.05) except for three of the four coffees treated with ethyl acetate regardless of whether or not they contained caffeine. Caffeinated ground coffee stimulated more acid secretion that did decaf ground coffees (P less than 0.05), but not more than a steam-treated caffeinated coffee. Instant coffees did not differ in acid-stimulating ability. Ground caffeinated coffee resulted in higher blood gastrin levels than other ground coffees (P less than 0.05). Freeze-dried instant coffee also tended toward higher gastrin stimulation. It is concluded that some of the observed variability in gastric response to coffee consumption can be traced to differences in how green coffee beans are processed. PMID:1551346

  18. Gastrin promotes the metastasis of gastric carcinoma through the β-catenin/TCF-4 pathway.

    PubMed

    Zhuang, Kun; Yan, Yuan; Zhang, Xin; Zhang, Jun; Zhang, Lingxia; Han, Kun

    2016-09-01

    Gastric cancer is the most common epithelial malignancy and the second leading cause of cancer-related death worldwide; metastasis is a crucial factor in the progression of gastric cancer. The present study applied gastrin-17 amide (G-17) in SGC7901 cells. The results showed that G-17 promoted the cell cycle by accelerating the G0/G1 phase and by increasing the cell proliferation rate by binding to the gastrin receptor. The migratory and invasive abilities of the SGC7901 cells were increased by G-17. The expression levels of matrix metalloproteinase (MMP)-7, MMP-9 and vascular endothelial growth factor (VEGF) were enhanced by G-17 as well. Moreover, G-17 caused the overexpression of β-catenin and TCF-4. G-17 also caused a preferential cytoplasmic and nuclear localization of β-catenin with a high TOP-FLASH activity. Finally, axin reduced the migratory and invasive abilities of the SGC7901 cells, and inhibited the expression of β-catenin, TCF-4, MMP-7, MMP-9 and VEGF; these effects were counteracted by adding G-17. In summary, the present study confirmed the proliferation and metastasis-promoting role of G-17 via binding to the gastrin receptor, and the β-catenin/TCF-4 pathway was found to be essential for mediating G-17-induced metastasis in gastric cancer. These results may provide a novel gene target for the treatment of gastric cancer. PMID:27430592

  19. COX-2, mPGES-1 and EP2 receptor immunohistochemical expression in canine and feline malignant mammary tumours.

    PubMed

    Millanta, F; Asproni, P; Canale, A; Citi, S; Poli, A

    2016-09-01

    Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E2 (PGE2 ) tumour-promoting activity has been confirmed and its production is controlled by Cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Evidence suggests that mPGES-1 and COX-2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX-2, mPGES-1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non-neoplastic tissues. COX-2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES-1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX-2, EP2 receptor and mPGES-1 expression was significantly higher in carcinomas than in non-neoplastic tissues and adenomas. COX-2, mPGES-1 and EP2 receptor expression was strongly associated. These findings support a role of the COX-2/PGE2 pathway in the pathogenesis of these tumours. PMID:24824420

  20. Tumour ablation: technical aspects

    PubMed Central

    Bodner, Gerd; Bale, Reto

    2009-01-01

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

  1. Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells.

    PubMed

    Liu, Tianbing; Konkalmatt, Prasad R; Yang, Yu; Jose, Pedro A

    2016-04-01

    The natriuretic effect of gastrin suggests a role in the coordinated regulation of sodium balance by the gastrointestinal tract and the kidney. The renal molecular targets and signal transduction pathways for such an effect of gastrin are largely unknown. Recently, we reported that gastrin induces NHE3 phosphorylation and internalization via phosphatidylinositol (PI) 3-kinase and PKCα. In this study, we show that gastrin induced the phosphorylation of human Na(+),K(+)-ATPase at serine 16, resulting in its endocytosis via Rab5 and Rab7 endosomes. The gastrin-stimulated phosphorylation of Na(+),K(+)-ATPase was dependent on PI 3-kinase because the phosphorylation was blocked by the PI 3-kinase inhibitor wortmannin. The phosphorylation of Na(+),K(+)-ATPase was also blocked by chelerythrine, a pan-PKC inhibitor, Gö-6976, a conventional PKC (cPKC) inhibitor, and BAPTA-AM, an intracellular calcium chelator, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The gastrin-mediated phosphorylation of Na(+),K(+)-ATPase was also inhibited by U-73122, a phospholipase C (PLC) inhibitor. These results suggest that gastrin regulates sodium hydrogen exchanger and pump in renal proximal tubule cells at the apical and basolateral membranes. PMID:26786777

  2. Functional pharmacology of H1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons

    PubMed Central

    Tabarean, I V

    2013-01-01

    BACKGROUND AND PURPOSE Histamine H1 receptors are highly expressed in hypothalamic neurons and mediate histaminergic modulation of several brain-controlled physiological functions, such as sleep, feeding and thermoregulation. In spite of the fact that the mouse is used as an experimental model for studying histaminergic signalling, the pharmacological characteristics of mouse H1 receptors have not been studied. In particular, selective and potent H1 receptor agonists have not been identified. EXPERIMENTAL APPROACH Ca2+ imaging using fura-2 fluorescence signals and whole-cell patch-clamp recordings were carried out in mouse preoptic/anterior hypothalamic neurons in culture. KEY RESULTS The H1 receptor antagonists mepyramine and trans-triprolidine potently antagonized the activation by histamine of these receptors with IC50 values of 0.02 and 0.2 μM respectively. All H1 receptor agonists studied had relatively low potency at the H1 receptors expressed by these neurons. Methylhistaprodifen and 2-(3-trifluoromethylphenyl)histamine had full-agonist activity with potencies similar to that of histamine. In contrast, 2-pyridylethylamine and betahistine showed only partial agonist activity and lower potency than histamine. The histamine receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptanecarboxamide (HTMT) had no agonist activity at the H1 receptors H1 receptors expressed by mouse preoptic/anterior hypothalamic neurons but displayed antagonist activity. CONCLUSIONS AND IMPLICATIONS Methylhistaprodifen and 2-(3-trifluoromethylphenyl)histamine were identified as full agonists of mouse H1 receptors. These results also indicated that histamine H1 receptors in mice exhibited a pharmacological profile in terms of agonism, significantly different from those of H1 receptors expressed in other species. PMID:23808378

  3. Comparison of estrogen and progesterone receptor expression in normal and tumor mammary tissues from dogs.

    PubMed

    Donnay, I; Rauïs, J; Devleeschouwer, N; Wouters-Ballman, P; Leclercq, G; Verstegen, J

    1995-09-01

    Concentrations of estrogen (ER) and progesterone (PR) receptors were measured by radioreceptor assay in tumor (n = 319) and normal (n = 166) mammary tissue from 248 bitches. Correlations between ER and PR and between receptor expression in tumor and normal mammary tissue from the same bitches were evaluated. The influence of tumor, clinical, or hormonal variables on receptor expression also was studied. Approximately 80% of tumor and 95% of normal mammary tissue expressed detectable concentrations of ER, PR, or both. Direct correlation was found between ER and PR concentrations in normal and tumor tissues. Median ER concentrations were significantly higher (46 +/- 47 fmol/mg of cytosolic protein vs 27 +/- 24 fmol/mg of cytosolic protein; P = 0.0002) in normal than in tumor tissue. On the other hand, PR concentrations were significantly higher (57 +/- 52 fmol/mg vs 77 +/- 99 fmol/mg; P = 0.03) in tumors (especially benign tumors) than in normal tissue. Poorly differentiated malignant tumors expressed lower concentrations of receptors than did benign or well differentiated malignant tumors. The ER and PR concentrations decreased with increasing size of the lesion. Hormonal status of the bitch significantly (P < 0.05) influenced receptor expression in normal tissue: bitches in the luteal phase of the estrous cycle had higher concentrations of ER (69 +/- 62 fmol/mg) than did ovariectomized bitches (24 +/- 19 fmol/mg) or bitches in anestrus (38 +/- 45 fmol/mg) or the follicular phase (13 +/- 7 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7486397

  4. Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus.

    PubMed

    Gangarossa, Giuseppe; Longueville, Sophie; De Bundel, Dimitri; Perroy, Julie; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-12-01

    The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor-expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ-Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network. PMID:22777829

  5. Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion

    PubMed Central

    Juengel, Eva; Krueger, Geraldine; Rutz, Jochen; Nelson, Karen; Werner, Isabella; Relja, Borna; Seliger, Barbara; Fisslthaler, Beate; Fleming, Ingrid; Tsaur, Igor

    2016-01-01

    Renal cell carcinoma (RCC) escapes immune recognition. To elaborate the escape strategy the influence of RCC cells on endothelial receptor expression and endothelial leukocyte adhesion was evaluated. Human umbilical vein endothelial cells (HUVEC) were co-cultured with the RCC cell line, Caki-1, with and without tumor necrosis factor (TNF)-alpha. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial (E)-selectin, standard and variants (V) of CD44 were then analysed in HUVEC, using flow cytometry and Western blot analysis. To determine which components are responsible for HUVEC-Caki-1 interaction causing receptor alteration, Caki-1 membrane fragments versus cell culture supernatant were applied to HUVECS. Adhesion of peripheral blood lymphocytes (PBL) and polymorphonuclear neutrophils (PMN) to endothelium was evaluated by co-culture adhesion assays. Relevance of endothelial receptor expression for adhesion to endothelium was determined by receptor blockage. Co-culture of RCC and HUVECs resulted in a significant increase in endothelial ICAM-1, VCAM-1, E-selectin, CD44 V3 and V7 expression. Previous stimulation of HUVECs with TNF-alpha and co-cultivation with Caki-1 resulted in further elevation of endothelial CD44 V3 and V7 expression, whereas ICAM-1, VCAM-1 and E-selectin expression were significantly diminished. Since Caki-1 membrane fragments also caused these alterations, but cell culture supernatant did not, cell-cell contact may be responsible for this process. Blocking ICAM-1, VCAM-1, E-selectin or CD44 with respective antibodies led to a significant decrease in PBL and PMN adhesion to endothelium. Thus, exposing HUVEC to Caki-1 results in significant alteration of endothelial receptor expression and subsequent endothelial attachment of PBL and PMN. PMID:26943029

  6. Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

    PubMed Central

    Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

    2014-01-01

    Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P < 0.05) and formed endothelial-like networks to a greater extent (P < 0.05) than SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P < 0.05), and an increased percentage of dNK cells expressed NKG2D at 10% oxygen (P < 0.05) compared to other oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

  7. [Studies on the clinical significance concerning the changes in serum pepsinogen-I and gastrin levels in aged patients with chronic gastritis].

    PubMed

    Hamada, Y; Kamiya, K; Koyama, M; Asaka, M; Matsushima, T; Myazaki, T; Kamiya, T

    1988-03-01

    Of 86 cases of aged patients with chronic gastritis treated with Trimebutine or Flutazolam, we evaluated the changes of serum pepsinogen-I and gastrin levels in their clinical courses from the points of the correlation with severity of chronic gastritis, aging phenomenon and the changes of symptom and endoscopic findings. In order to elucidate the multidimensional interrelation among these items, we used Hayashi's quantification theory II as a conventional analysis method. In aged patients, generally, although the serum gastrin levels were rather high compared with younger generation, the serum pepsinogen-I levels were consistently low throughout their clinical courses. There were some correlation between the levels of serum gastrin and the severity of chronic gastritis. When the drugs were effective on improving the condition of the disease, the level of gastrin revealed gradual decrease. These changes of gastrin were more typical in patients treated with Trimebutine. PMID:2898425

  8. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor–Positive Tumors

    PubMed Central

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J.G.; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C.

    2011-01-01

    In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor–positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET–computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor–mediated uptake (p = .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor–positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor–positive tumors in humans. PMID:21439259

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

    PubMed Central

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

    2016-01-01

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

  10. Gastrointestinal stromal tumour.

    PubMed

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

    2013-09-14

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

  11. Transport processes in tumours.

    PubMed

    Quastel, J H

    1965-12-01

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

  12. Breast tumour angiogenesis

    PubMed Central

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

    2007-01-01

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

  13. [Tumours and liver transplants].

    PubMed

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

    2015-01-01

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

  14. An animal model allowing controlled receptor expression for molecular ultrasound imaging.

    PubMed

    Saini, Reshu; Sorace, Anna G; Warram, Jason M; Mahoney, Marshall J; Zinn, Kurt R; Hoyt, Kenneth

    2013-01-01

    Reported in this study is an animal model system for evaluating targeted ultrasound (US) contrast agents binding using adenoviral (Ad) vectors to modulate cellular receptor expression. An Ad vector encoding an extracellular hemagglutinin (HA) epitope tag and a green fluorescent protein (GFP) reporter was used to regulate receptor expression. A low and high receptor density (in breast cancer tumor bearing mice) was achieved by varying the Ad dose with a low plaque forming unit (PFU) on day 1 and high PFU on day 2 of experimentation. Targeted US contrast agents, or microbubbles (MB), were created by conjugating either biotinylated anti-HA or IgG isotype control antibodies to the MB surface with biotin-streptavidin linkage. Targeted and control MBs were administered on both days of experimentation and contrast-enhanced US (CEUS) was performed on each mouse using MB flash destruction technique. Signal intensities from MBs retained within tumor vasculature were analyzed through a custom Matlab program. Results showed intratumoral enhancement attributable to targeted MB accumulation was significantly increased from the low Ad vector dosing and the high Ad vector dosing (p = 0.001). Control MBs showed no significant differences between day 1 and day 2 imaging (p = 0.96). Additionally, targeted MBs showed a 10.5-fold increase in intratumoral image intensity on day 1 and an 18.8-fold increase in image intensity on day 2 compared with their control MB counterparts. PMID:23122640

  15. Altered sensitivity to excitotoxic cell death and glutamate receptor expression between two commonly studied mouse strains

    PubMed Central

    Finn, Rozzy; Kovács, Attila D.; Pearce, David A.

    2011-01-01

    Alterations in glutamatergic synapse function have been implicated in the pathogenesis of many different neurological disorders including ischemia, epilepsy, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. While studying glutamate receptor function in juvenile Batten disease on the C57BL/6J and 129S6/SvEv mouse backgrounds, we noticed differences unlikely to be due to mutation difference alone. We report here that primary cerebellar granule cell cultures from C57BL/6J mice are more sensitive to NMDA-mediated cell death. Moreover, sensitivity to AMPA-mediated excitotoxicity is more variable and is dependent upon the treatment conditions and age of the cultures. Glutamate receptor surface expression levels examined in vitro by in situ ELISA and in vivo by Western blot in surface cross-linked cerebellar samples indicated that these differences in sensitivity are likely due to strain-dependent differences in cell surface receptor expression levels. We propose that differences in glutamate receptor expression and in excitotoxic vulnerability should be taken into consideration in the context of characterizing disease models on the C57BL/6J and 129S6/SvEv mouse backgrounds. PMID:20544821

  16. The Triggering Receptor Expressed on Myeloid cells-1: A new player during acute myocardial infarction.

    PubMed

    Jérémie, Lemarié; Amir, Boufenzer; Marc, Derive; Sébastien, Gibot

    2015-10-01

    Following myocardial ischemia, an intense activation of the immune system occurs that leads to inflammatory cytokines and chemokines production and to the recruitment of neutrophils and mononuclear cells in the infarcted area. Although pro-inflammatory signals initiate the cellular events necessary for scar formation, excessive and prolonged inflammation promotes deleterious cardiac remodeling and dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a highly conserved immune-receptor expressed by neutrophils and monocytes that acts as an amplifier of the innate immune response. Blockade of TREM-1 activation protects from hyper-responsiveness and death during severe infections. Here we review the role of TREM-1 in orchestrating the inflammatory response that follows MI. TREM-1 deletion (Trem-1-/-) or modulation by the use of a short inhibitory peptide (LR12) dampens myocardial inflammation, limits leukocyte recruitment, and improves heart function and survival in mice or pigs. Moreover, the soluble form of TREM-1 (sTREM-1) is found in the plasma of patients suffering from an acute MI and its concentration is an independent predictor of death. This suggests that TREM-1 may constitute a new therapeutic target during acute MI. PMID:26318764

  17. Testicular germ cell tumours.

    PubMed

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

    2016-04-23

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

  18. GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI

    PubMed Central

    Pu, Fan; Qiao, Jingjuan; Xue, Shenghui; Yang, Hua; Patel, Anvi; Wei, Lixia; Hekmatyar, Khan; Salarian, Mani; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is differentially expressed on the surfaces of various diseased cells, including prostate and lung cancer. However, monitoring temporal and spatial expression of GRPR in vivo by clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capability and tumor penetration. Here, we report the development of a GRPR-targeted MRI contrast agent by grafting the GRPR targeting moiety into a scaffold protein with a designed Gd3+ binding site (ProCA1.GRPR). In addition to its strong binding affinity for GRPR (Kd = 2.7 nM), ProCA1.GRPR has high relaxivity (r1 = 42.0 mM−1s−1 at 1.5 T and 25 °C) and strong Gd3+ selectivity over physiological metal ions. ProCA1.GRPR enables in vivo detection of GRPR expression and spatial distribution in both PC3 and H441 tumors in mice using MRI. ProCA1.GRPR is expected to have important preclinical and clinical implications for the early detection of cancer and for monitoring treatment effects. PMID:26577829

  19. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

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

  20. Tumours of the thymus

    PubMed Central

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

    1967-01-01

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

  1. Tumours of the ovary

    PubMed Central

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

    1976-01-01

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

  2. Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  3. Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  4. Evaluation of the hormones responsible for the gastrointestinal motility in cattle with displacement of the abomasum; ghrelin, motilin and gastrin.

    PubMed

    Ozturk, A S; Guzel, M; Askar, T K; Aytekin, I

    2013-06-15

    This study provides the evidence of increased serum gastrointestinal motility hormone concentrations including ghrelin, motilin and gastrin in cattle with displacement of abomasum (DA). In this study, 38 cows with DA (21 left DA (LDA) and 17 right DA (RDA)) and 15 healthy controls were included. All cattle with DA were at the stage of postpartum one to eight weeks, and had clinical signs including anorexia, decreased milk yield and scanty, pasty faeces. Serum ghrelin, motilin and gastrin concentrations, and leptin concentration which is a functional antagonist of ghrelin, were determined by ELISA. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), Na, K, Cl, Ca and P concentrations were measured by spectrophotometer. In serum biochemical analysis, increases were seen on the serum ALT, AST and GGT activities; however, serum Na, K, Cl and P concentrations decreased in abomasal displacement compared with the control animals. The serum ghrelin, motilin and gastrin concentrations increased in the cattle with LDA and RDA, as compared with those in the healthy controls. On the other hand, serum leptin concentration decreased in the cattle with DA compared with the controls. Increases in the serum ghrelin, motilin and gastrin concentrations might be attributed to activation of gastrointestinal motility hormones to enhance of gastric emptying in impaired gastric motility and/or outlet occlusion in displaced abomasum. PMID:23723101

  5. Clinical review: Role of triggering receptor expressed on myeloid cells-1 during sepsis

    PubMed Central

    Gibot, Sébastien

    2005-01-01

    Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified molecule that is involved in monocytic activation and in the inflammatory response. It belongs to a family related to the natural killer cell receptors and is expressed on neutrophils, mature monocytes and macrophages. The inflammatory response mediated by Toll-like receptor-2 and -4 stimulation is amplified by the engagement of TREM-1. The expression of membrane-bound TREM-1 is greatly increased on monocytes during sepsis. Moreover, infection induces the release of a soluble form of this receptor, which can be measured in biological fluid and may be useful as a diagnostic tool. Modulation of the TREM-1 signalling pathway by the use of small synthetic peptides confers interesting survival advantages during experimental septic shock in mice, even when this teatment is administered late after the onset of sepsis. PMID:16277737

  6. Normal Morphology and Hormone Receptor Expression in the Male California sea lion (Zalophus californianus) Genital Tract

    PubMed Central

    Colegrove, Kathleen M.; Gulland, Frances M. D.; Naydan, Diane K.; Lowenstine, Linda J.

    2010-01-01

    Histomorphology and estrogen α (ER α), and progesterone receptor (PR) expression were evaluated in free-ranging stranded male California sea lions (Zalophus californianus). Hormone receptor expression was evaluated using an immunohistochemical technique with monoclonal antibodies. Estrogen and progesterone receptors were identified in the efferent ductules, prostate gland, corpus cavernosa, corpus spongiosium, penile urethra, and in the epithelium and stroma of both the penis and prepuce. In the some tissues, ER α expression was more intense in the stroma, emphasizing the importance of the stroma in hormone – mediated growth and differentiation of reproductive organs. To our knowledge, this is the first study to localize ER α and PR to the epithelium of the glans penis. The results of this investigation add to the general knowledge of male California sea lion reproduction and suggest that estrogens could have a role in the function of the male reproductive tract. PMID:19768750

  7. Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells

    PubMed Central

    Valentini, Mariagrazia; Piermattei, Alessia; Di Sante, Gabriele; Delogu, Giovanni; Ria, Francesco

    2014-01-01

    A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota. PMID:25147831

  8. Tonotopic changes in GABA receptor expression in guinea pig inferior colliculus after partial unilateral hearing loss.

    PubMed

    Dong, S; Rodger, J; Mulders, W H A M; Robertson, D

    2010-06-25

    Immunohistochemistry was used to investigate the topographic distribution of the alpha1 subunit of the GABA receptor (GABRA1) in guinea pig inferior colliculus after treatments that caused a unilateral loss of peripheral neural sensitivity in the high-frequency regions of the cochlea. Both forms of treatment (direct mechanical lesion of the cochlea and acoustic overstimulation) resulted in a significant decrease in GABRA1 labeling in regions of the contralateral inferior colliculus in which high-frequency sound stimuli are represented. This localized region of reduced inhibitory receptor expression corresponds to the region in which hyperactivity of inferior colliculus neurons has been shown to develop after such treatments. The results strengthen the notion of a causal link between reduced GABRA1 expression and neural hyperactivity in central auditory nuclei and provide a possible mechanism for the development of phantom auditory sensations, or tinnitus. PMID:20438718

  9. Notch Receptor Expression in Neurogenic Regions of the Adult Zebrafish Brain

    PubMed Central

    de Oliveira-Carlos, Vanessa; Ganz, Julia; Hans, Stefan; Kaslin, Jan; Brand, Michael

    2013-01-01

    The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches. PMID:24039926

  10. Functional characteristics of enhanced Fc receptor expression of beta 2 integrin-deficient bovine mononuclear phagocytes.

    PubMed

    Nagahata, H; Higuchi, H; Goji, N; Noda, H; Kuwabara, M

    1996-01-01

    Fc receptor expression, cytoplasmic Ca2+ signaling, chemiluminescent (CL) response, and electron spin resonance (ESR) combined with spin trapping of blood mononuclear phagocytes from control heifers and a heifer with leukocyte adhesion deficiency (LAD) were evaluated to elucidate the relationships between complement receptor type 3 (CR3) and Fc receptor expression and their functional responses. The mean fluorescence intensity of fluorescein isothiocyanate (FITC)-conjugated anti-bovine IgG bound to mononuclear phagocytes from the heifer with LAD was 1.8-fold higher than that of control heifers. The mean increments of cytoplasmic Ca2+ concentrations of mononuclear phagocytes from the heifer with LAD stimulated with OPZ, Agg-IgG, and PMA were 39.4 (P < 0.05), 118, and 71.6% compared with those of control heifers. A 1.27-fold increase in the CL response relative to control heifers was detected when mononuclear phagocytes from the heifer with LAD were stimulated with Agg-IgG. The OPZ-induced CL response of mononuclear phagocytes from the heifer with LAD was significantly (P < 0.05) decreased, whereas the PMA-induced CL response was similar to that of control heifers. The ESR spectrum of mononuclear phagocytes from the heifer with LAD was increased when stimulated with Agg-IgG, and was impaired when stimulated by OPZ compared with that of control heifers. The ESR spectrum of mononuclear phagocytes stimulated with PMA was similar in control heifers and the heifer with LAD. Fc receptors on mononuclear phagocytes from the heifer with LAD were enhanced, and their cytoplasmic Ca2+ signaling, CL response, and ESR-spin trapping when stimulated with Agg-IgG and OPZ appeared to be associated with enhanced Fc receptors. PMID:8805104

  11. 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation

    PubMed Central

    Samarajeewa, Anshula; Goldemann, Lolita; Vasefi, Maryam S.; Ahmed, Nawaz; Gondora, Nyasha; Khanderia, Chandni; Mielke, John G.; Beazely, Michael A.

    2014-01-01

    The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands. PMID:25426041

  12. Radiotherapy for ocular tumours.

    PubMed

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

    2013-02-01

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

  13. Radiotherapy for ocular tumours

    PubMed Central

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

    2013-01-01

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

  14. Immunology of naturally transmissible tumours.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

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

  15. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

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

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

    PubMed

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

    2013-08-01

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

  17. ANALYSIS OF ANDROGEN- AND EGF-RECEPTOR EXPRESSION IN THE FETAL RAT PHALLUS AFTER EXPOSURE TO VINCLOZOLIN

    EPA Science Inventory

    Analysis of Androgen- and EGF-Receptor Expression in the Fetal Rat Phallus After Exposure to Vinclozolin
    Cynthia Wolf1,2, Barbara Abbott1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
    1USEPA, ORD, NHEERL, RTD, RTP, NC 27711, 2NCSU, Environmental and Molecular Toxicology, Ral...

  18. Effects of avian triggering receptor expressed on myeloid cells (TREM-A1) activation on heterophil functional activites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel class of innate receptors called the triggering receptors expressed on myeloid cells (TREM) has been discovered and shown to be involved in innate inflammatory responses. The TREM family has been found in the chicken genome and consists of one activating gene (TREM-A1) and two inhibitory ge...

  19. Tumour Cell Heterogeneity

    PubMed Central

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

    2016-01-01

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

  20. Effect of a somatostatin analogue (SMS 201-995) on antral gastrin cell hyperplasia and hypergastrinemia induced by a histamine H2-receptor antagonist.

    PubMed

    Kimura, K

    1993-05-01

    The effect of a somatostatin analogue, SMS 201-995 (SMS), on antral gastrin cell hyperplasia (AGH) and hypergastrinemia associated with 14-day administration of the histamine H2-receptor antagonist (H2-RA) famotidine was studied in rats. When the famotidine group was compared with the control group, the antral gastrin cell (G-cell) number was significantly increased (P < 0.01) by approximately twofold, and the serum gastrin level was significantly increased (P < 0.01) by approximately sixfold. When the famotidine+SMS group was compared with the famotidine group, the G-cell number was significantly decreased (P < 0.01) by approximately 30%, and the serum gastrin level was significantly decreased (P < 0.01) by approximately 40%. These findings suggest that SMS may be useful for inhibiting AGH and hypergastrinemia induced by long-term H2-RA administration. PMID:8511502

  1. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

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

  2. Characterization of the detergent solubilized receptor for gastrin-releasing peptide

    SciTech Connect

    Cirillo, D.; Naldini, L.; Moody, T.W.; Comoglio, P.; Schlessinger, J.; Kris, R. )

    1990-07-01

    Properties of detergent solubilized gastrin-releasing peptide receptor were investigated. Swiss 3T3 membranes were covalently labeled with ({sup 125}I)GRP and homobifunctional cross-linkers. A major labeled protein of 75 kDa was resolved using SDS-polyacrylamide gel electrophoresis. When the same preparation was solubilized with zwitterionic detergent and analyzed under nondenaturing conditions the protein bound radioactivity was resolved in two different peaks, a major one of apparent molecular weight 220,000 (peak 1) and a minor one of 80,000 (peak 2) both containing the 75 kDa protein. Specific ligand binding activity also eluted with peak 1. These results indicate that the active form of bombesin/GRP receptor is a large complex containing the 75 kDa ligand binding domain.

  3. Transient Receptor Potential Canonical 1 (TRPC1) Channels as Regulators of Sphingolipid and VEGF Receptor Expression

    PubMed Central

    Asghar, Muhammad Yasir; Magnusson, Melissa; Kemppainen, Kati; Sukumaran, Pramod; Löf, Christoffer; Pulli, Ilari; Kalhori, Veronica; Törnquist, Kid

    2015-01-01

    The identity of calcium channels in the thyroid is unclear. In human follicular thyroid ML-1 cancer cells, sphingolipid sphingosine 1-phosphate (S1P), through S1P receptors 1 and 3 (S1P1/S1P3), and VEGF receptor 2 (VEGFR2) stimulates migration. We show that human thyroid cells express several forms of transient receptor potential canonical (TRPC) channels, including TRPC1. In TRPC1 knockdown (TRPC1-KD) ML-1 cells, the basal and S1P-evoked invasion and migration was attenuated. Furthermore, the expression of S1P3 and VEGFR2 was significantly down-regulated. Transfecting wild-type ML-1 cells with a nonconducting TRPC1 mutant decreased S1P3 and VEGFR2 expression. In TRPC1-KD cells, receptor-operated calcium entry was decreased. To investigate whether the decreased receptor expression was due to attenuated calcium entry, cells were incubated with the calcium chelator BAPTA-AM (1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). In these cells, and in cells where calmodulin and calmodulin-dependent kinase were blocked pharmacologically, S1P3 and VEGFR2 expression was decreased. In TRPC1-KD cells, both hypoxia-inducible factor 1α expression and the secretion and activity of MMP2 and MMP9 were attenuated, and proliferation was decreased in TRPC1-KD cells. This was due to a prolonged G1 phase of the cell cycle, a significant increase in the expression of the cyclin-dependent kinase inhibitors p21 and p27, and a decrease in the expression of cyclin D2, cyclin D3, and CDK6. Transfecting TRPC1 to TRPC1-KD cells rescued receptor expression, migration, and proliferation. Thus, the expression of S1P3 and VEGFR2 is mediated by a calcium-dependent mechanism. TRPC1 has a crucial role in this process. This regulation is important for the invasion, migration, and proliferation of thyroid cancer cells. PMID:25971967

  4. Correlation of leptin receptor expression with BMI in differential grades of human meningiomas

    PubMed Central

    RUTKOWSKI, ROBERT; RESZEC, JOANNA; HERMANOWICZ, ADAM; CHRZANOWSKI, ROBERT; LYSON, TOMASZ; MARIAK, ZENON; CHYCZEWSKI, LECH

    2016-01-01

    Meningioma is one of the most common primary brain tumor, especially in postmenopausal women. The most important risk factors include radiation, primary head injury or genetic alterations, however it is currently unclear why postmenopausal women are predominantly affected. The aim of the present study was to evaluate leptin receptor (LEPR) expression and body mass index (BMI) in patients with meningiomas of differential grades. Specimens of 158 meningiomas were classified as either G1 (low-grade meningiomas, n=114) or G2/G3 (high-grade meningiomas, n=44). Immunohistochemistry was performed to assess LEPR expression. The mean BMIs of the female and male patient groups were 28.43±5.29 and 23.93±4.66, respectively. Mean BMI was significantly higher in the female group, by ~4.50 kg/m2. Patient age significantly correlated with LEPR expression, with the highly positive (++) and positive (+) groups having mean ages of 62.3±12.07 and 52.3±13.04, respectively. A strong positive correlation (r=0.73) was observed between leptin receptor expression and BMI, with the LEPR (++) group having a mean BMI of 30.11±4.49, compared to 22.12±2.48 for the LEPR (+) group. Furthermore, in the low-grade meningioma group, mean BMI was higher in female patients than male patients (28.13±5.54 and 25.38±4.57, respectively; P=0.01). Additionally, there was strong positive correlation between BMI and leptin receptor expression in the low-grade meningioma group (r=0.69). For the high-grade meningioma group, mean BMI was 29.49±4.26 and 21.76±3.98 in female and male patients, respectively, and LEPR expression strongly correlated with BMI in this group (r=0.80). The present study demonstrates a correlation between patient BMI, age, and LEPR expression status in low- and high-grade meningiomas. Our results indicate that in addition to endogenous hormones, such as estrogen or progesterone, or fatty tissue-associated proinflammatory cytokines, LEPR expression status may be a risk factor for

  5. Glomus tumour of the stomach.

    PubMed

    Troller, Rebekka; Soll, Christopher; Breitenstein, Stefan

    2016-01-01

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

  6. 1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms.

    PubMed Central

    Kane, K F; Langman, M J; Williams, G R

    1995-01-01

    Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy. Images Figure 1 Figure 2 PMID:7883226

  7. Fighting experience alters brain androgen receptor expression dependent on testosterone status

    PubMed Central

    Li, Cheng-Yu; Earley, Ryan L.; Huang, Shu-Ping; Hsu, Yuying

    2014-01-01

    Contest decisions are influenced by the outcomes of recent fights (winner–loser effects). Steroid hormones and serotonin are closely associated with aggression and therefore probably also play important roles in mediating winner–loser effects. In mangrove rivulus fish, Kryptolebias marmoratus, individuals with higher testosterone (T), 11-ketotestosterone and cortisol levels are more capable of winning, but titres of these hormones do not directly mediate winner–loser effects. In this study, we investigated the effects of winning/losing experiences on brain expression levels of the receptor genes for androgen (AR), oestrogen α/β (ERα/β), glucocorticoid (GR) and serotonin (5-HT1AR). The effect of contest experience on AR gene expression depended on T levels: repeated losses decreased, whereas repeated wins increased AR gene expression in individuals with low T but not in individuals with medium or high T levels. These results lend strong support for AR being involved in mediating winner–loser effects, which, in previous studies, were more detectable in individuals with lower T. Furthermore, the expression levels of ERα/β, 5-HT1AR and GR genes were higher in individuals that initiated contests against larger opponents than in those that did not. Overall, contest experience, underlying endocrine state and hormone and serotonin receptor expression patterns interacted to modulate contest decisions jointly. PMID:25320171

  8. GABAA Receptor Expression in the Forebrain of Ataxic Rolling Nagoya Mice.

    PubMed

    Nielsen, Elsebet Østergaard; Kaja, Simon

    2014-01-01

    The human CACNA1A gene encodes the pore-forming α1 subunit of CaV2.1 (P/Q-type) calcium channels and is the locus for several neurological disorders, including episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6) and Familial Hemiplegic Migraine type 1 (FHM1). Several spontaneous mouse Cacna1a mutant strains exist, among them Rolling Nagoya (tg (rol)), carrying the R1262G point mutation in the mouse Cacna1a gene. tg (rol) mice display a phenotype of severe gait ataxia and motor dysfunction of the hind limbs. At the functional level, the R1262G mutation results in a positive shift of the activation voltage of the CaV2.1 channel and reduced current density. γ-Aminobutyric acid type A (GABAA) receptor subunit expression depends critically on neuronal calcium influx, and GABAA receptor dysfunction has previously been described for the cerebellum of tg (rol) and other ataxic Cacna1a mutant mice. Given the expression pattern of CaV2.1, it was hypothesized that calcium dysregulation in tg (rol) might affect GABAA receptor expression in the forebrain. Herein, functional GABAA receptors in the forebrain of tg (rol) mice were quantified and pharmacologically dissociated using [(3)H] radioligand binding. No gross changes to functional GABAA receptors were identified. Future cell type-specific analyses are required to identify possible cortical contributions to the psychomotor phenotype of tg (rol) mice. PMID:25309056

  9. A short review of twin pregnancy and how oxytocin receptor expression may differ in multiple pregnancy.

    PubMed

    Turton, Peter; Neilson, James P; Quenby, Siobhan; Burdyga, Theodor; Wray, Susan

    2009-05-01

    During a multiple pregnancy, the mother and her fetuses are exposed to a variety of risks during both pregnancy and labour. The most notable of these risks is that of pre-term labour and its associated sequelae. Whilst much research has been directed towards understanding the mechanisms of uterine contractility, very little research has focussed on how contractility in multiple pregnancy differs from contractility in the singleton pregnancy. The aim of this paper is to review the changing prevalence and risks of a twin pregnancy, as well as reviewing what is known about myometrium from multiple pregnancies. The paper ends by discussing how oxytocin receptor expression may differ in twin pregnancy, based on the evidence of animal models, as well as presenting our own evidence of how oxytocin affects myometrium from twin pregnancies. We highlight the lack of the basic information needed to characterize human myometrium in twin pregnancies. Of particular note is the lack of supporting data for the hypothesis that stretch is responsible for earlier activation of the uterus in multiple pregnancy. New hypotheses based on increased experimental work are called for. Such information may throw light on specific mechanisms leading to the increased incidence of pre-term delivery in twins. PMID:19303192

  10. A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces.

    PubMed

    Tang, Yanjuan; Zhang, Shaolian; Wen, Qingqing; Huang, Hongxing; Yang, Peihui

    2015-06-30

    A sensitive electrochemiluminescence (ECL) strategy for evaluating the epidermal growth factor receptor (EGFR) expression level on cell surfaces was designed by integrating the specific recognition of EGFR expressed on MCF-7 cell surfaces with an epidermal growth factor (EGF)-funtionalized CdS quantum dots (CdSQDs)-capped magnetic bead (MB) probe. The high sensitivity of ECL probe of EGF-funtionalized CdSQD-capped-MB was used for competitive recognition with EGFR expressed on cell surfaces with recombinant EGFR protein. The changes of ECL intensity depended on both the cell number and the expression level of EGFR receptor on cell surfaces. A wide linear response to cells ranging from 80 to 4×10(6)cellsmL(-1) with a detection limit of 40cellsmL(-1) was obtained. The EGF-cytosensor was used to evaluate EGFR expression levels on MCF-7 cells, and the average number of EGFR receptor on single MCF-7 cells was 1.35×10(5) with the relative standard deviation of 4.3%. This strategy was further used for in-situ and real-time evaluating EGFR receptor expressed on cell surfaces in response to drugs stimulation at different concentration and incubation time. The proposed method provided potential applications in the detection of receptors on cancer cells and anticancer drugs screening. PMID:26041531

  11. Glucocorticoid receptor expression and sub-cellular localization in dopamine neurons of the rat midbrain.

    PubMed

    Hensleigh, E; Pritchard, L M

    2013-11-27

    Stress plays an important role in the development of addiction. Animals subjected to stress exhibit sensitized responses to psychostimulant drugs, and this sensitized response is associated with functional adaptations of the mesolimbic dopamine system. These adaptations likely arise from direct or indirect effects of glucocorticoids on dopaminergic neurons. Though glucocorticoid receptor expression in midbrain dopaminergic neurons has been examined in previous studies, results have been somewhat equivocal. We sought to clarify this issue by analyzing tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) co-localization in the rat midbrain by dual fluorescence immunohistochemistry. We also examined sub-cellular localization of the GR in rat midbrain neurons after acute restraint stress. Adult Long-Evans rats were sacrificed 0, 30, 60 or 120min after 30min of restraint stress. A control group did not undergo restraint. Blood samples were collected immediately before and after restraint for measurement of plasma corticosterone by enzyme immunoassay. Glucocorticoid receptors were observed in dopaminergic neurons in both the substantia nigra (SN) and ventral tegmental area (VTA). The degree of co-localization of TH and GR did not differ between the VTA and the SN. All animals subjected to stress exhibited significant increases in plasma corticosterone. Significant translocation of GR signal to cell nuclei was observed after restraint in the SN, but not in the VTA. These results suggest that stress-induced glucocorticoid secretion could trigger functional changes in the mesolimbic dopamine system by direct activation of glucocorticoid receptors in dopaminergic neurons. PMID:24121048

  12. Delayed Gelatinase Inhibition Induces Reticulon 4 Receptor Expression in the Peri-Infarct Cortex.

    PubMed

    Nardai, Sándor; Dobolyi, Arpád; Skopál, Judit; Lakatos, Kinga; Merkely, Béla; Nagy, Zoltán

    2016-04-01

    Matrix metalloproteinase (MMP) inhibition can potentially prevent hemorrhagic transformation following cerebral infarction; however, delayed-phase MMP activity is also necessary for functional recovery after experimental stroke. We sought to identify potential mechanisms responsible for the impaired recovery associated with subacute MMP inhibition in a transient middle cerebral artery occlusion model of focal ischemia in CD rats. Gelatinase inhibition was achieved by intracerebral injection of the Fn-439 MMP inhibitor 7 days after stroke. Treatment efficacy was determined on day 9 by in situ gelatin zymography. The peri-infarct cortex was identified by triphenyl tetrazolium chloride staining, and tissue samples were dissected for TaqMan array gene-expression study. Of 84 genes known to influence poststroke regeneration, we found upregulation of mRNA for the reticulon 4 receptor (Rtn4r), a major inhibitor of regenerative nerve growth in the adult CNS, and borderline expression changes for 3 additional genes (DCC, Jun, andNgfr). Western blot confirmed increased Rtn4r protein in the peri-infarct cortex of treated animals, and double immunolabeling showed colocalization primarily with the S100 astrocyte marker. These data suggest that increased Rtn4 receptor expression in the perilesional cortex may contribute to the impaired regeneration associated with MMP inhibition in the subacute phase of cerebral infarction. PMID:26945033

  13. Intranasally Administered Neuropeptide S (NPS) Exerts Anxiolytic Effects Following Internalization Into NPS Receptor-Expressing Neurons

    PubMed Central

    Ionescu, Irina A; Dine, Julien; Yen, Yi-Chun; Buell, Dominik R; Herrmann, Leonie; Holsboer, Florian; Eder, Matthias; Landgraf, Rainer; Schmidt, Ulrike

    2012-01-01

    Experiments in rodents revealed neuropeptide S (NPS) to constitute a potential novel treatment option for anxiety diseases such as panic and post-traumatic stress disorder. However, both its cerebral target sites and the molecular underpinnings of NPS-mediated effects still remain elusive. By administration of fluorophore-conjugated NPS, we pinpointed NPS target neurons in distinct regions throughout the entire brain. We demonstrated their functional relevance in the hippocampus. In the CA1 region, NPS modulates synaptic transmission and plasticity. NPS is taken up into NPS receptor-expressing neurons by internalization of the receptor–ligand complex as we confirmed by subsequent cell culture studies. Furthermore, we tracked internalization of intranasally applied NPS at the single-neuron level and additionally demonstrate that it is delivered into the mouse brain without losing its anxiolytic properties. Finally, we show that NPS differentially modulates the expression of proteins of the glutamatergic system involved inter alia in synaptic plasticity. These results not only enlighten the path of NPS in the brain, but also establish a non-invasive method for NPS administration in mice, thus strongly encouraging translation into a novel therapeutic approach for pathological anxiety in humans. PMID:22278093

  14. The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice.

    PubMed

    do Amaral, Vinícius Cestari; Carvalho, Kátia Candido; Maciel, Gustavo Arantes Rosa; Simoncini, Tommaso; da Silva, Priscilla Ludovico; Marcondes, Rodrigo Rodrigues; Soares, José Maria; Baracat, Edmund Chada

    2015-02-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor. PMID:25299230

  15. [Modulation of Fcgamma and C3b receptor expression by marine bioglycans in mouse splenocytes].

    PubMed

    Zaporozhets, T S

    2003-01-01

    Investigation of polysacharide immunomodulators of marine origin was performed--mitilane, alpha-1,4;1,6-D-glucane, isolated from midia Crenomytilus grayanus, and translam--beta-1,3;1,6-D-glucane isolated from marine algae Laminaria cichorioides were compared. Mechanisms of phagocytes cells activation were investigated. Dose-dependent ability of investigated bioglycanes to facilitate Fc gamma R [symbol: see text] C3bR expression at mice splenocytes was demonstrated in vivo and in vitro. The effect depended on immunomodulator type, incubation conditions, dose, period of incubation in vitro and by splenocytes population used for Fc gamma R and C3bR identification. It was shown that C3bR expression was more enhanced by immunomodulators than Fc gamma R expression. For Fc gamma R induction on lymphocytes membranes the presence of phagocytes cell (macrophages and neutrophils) is obligatory. Mitilane, containing alpha-1,4;1,6-D-glucane and some amount of protein is more effective in stimulation of membrane receptors expression than translam--beta-1,3;1,6-D-glucane. The results of investigation demonstrates the possibility to use marine bioglicanes as activators of Fc gamma R and C3bR activity, that is the base for control of pathological processes, related to immune system. PMID:12914116

  16. Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2).

    PubMed

    Atagi, Yuka; Liu, Chia-Chen; Painter, Meghan M; Chen, Xiao-Fen; Verbeeck, Christophe; Zheng, Honghua; Li, Xia; Rademakers, Rosa; Kang, Silvia S; Xu, Huaxi; Younkin, Steven; Das, Pritam; Fryer, John D; Bu, Guojun

    2015-10-23

    Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Here, we report apolipoprotein E (apoE) as a novel ligand for TREM2. Using a biochemical assay, we demonstrated high-affinity binding of apoE to human TREM2. The functional significance of this binding was highlighted by increased phagocytosis of apoE-bound apoptotic N2a cells by primary microglia in a manner that depends on TREM2 expression. Moreover, when the AD-associated TREM2-R47H mutant was used in biochemical assays, apoE binding was vastly reduced. Our data demonstrate that apoE-TREM2 interaction in microglia plays critical roles in modulating phagocytosis of apoE-bound apoptotic neurons and establish a critical link between two proteins whose genes are strongly linked to the risk for AD. PMID:26374899

  17. Borderline ovarian tumours.

    PubMed

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

    2012-06-01

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

  18. Tumours of the kidney

    PubMed Central

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

    1976-01-01

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

  19. Clinical features of gastroenteropancreatic tumours

    PubMed Central

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

    2015-01-01

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

  20. Biophysical models of tumour growth

    NASA Astrophysics Data System (ADS)

    Tracqui, P.

    2009-05-01

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

  1. Pancreatic acinar cells: effect of acetylcholine, pancreozymin, gastrin and secretin on membrane potential and resistance in vivo and in vitro.

    PubMed Central

    Petersen, O H; Ueda, N

    1975-01-01

    1. Intracellular recordings of membrane potential and input resistance have been made in vivo and in vitro from the exocrine acinar cells of rat pancreas using indwelling glass micro-electrodes. 2. The resting cell membrane potential and input resistance in the in vivo experiments were not markedly different from the values obtained in the in vitro experiments. The effect of both acetylcholine (ACh) and pancreozymin (CCK-Pz) on the pancreas in vivo as well as in vitro was to reduce both the acinar cell membrane potential and the input resistance narkedly. The amplitude of the evoked depolarization and the change in input resistance evoked by supramaximal stimuli were of the same magnitude in both types of preparations. 3. Gastrin had an effect on the acinar cell potential and resistance which was indistinguishable from that of CCK-Pz or ACh. The effect of gastrin or CCK-Pz was, in contrast to that of ACh, not influenced by the presence of atropine. The reversal potential for the gastrin evoked potential change was about -20 mV. 4. Secretin in doses producing maximal volume secretion in vivo had no effect on acinar cell membrane potential and input resistance. 5. Dibutyryl cyclic AMP (5mM) and cyclic GMP (1mM) had no effect on cell membrane potential or resistance. 6. It is concluded that the in vitro superfused pancreas segment preparation is a useful model system in electrophysiological studies since it functions essentially as the in vivo preparation. In contrast to both gastrin and CCK-Pz, secretin has no effect on the bioelectrical properties of the acinar cells, indicating that there are no physiologically important secretin receptors in rat acinar cells. PMID:168355

  2. Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid secretion and rabeprazoleinduced hypergastrinaemia in healthy subjects

    PubMed Central

    Boyce, Malcolm; Dowen, Sally; Turnbull, Gillian; van den Berg, Frans; Zhao, Chun-Mei; Chen, Duan; Black, James

    2015-01-01

    Aims To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. Methods Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal. Results All treatments similarly inhibited pentagastrin-stimulated gastric acid secretion. All treatments increased serum gastrin, but the combination and rabeprazole did so more than netazepide alone. The combination also reduced basal acid secretion. Rabeprazole increased plasma CgA, whereas netazepide and the combination reduced it. None of the biopsies showed enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led neither to rebound hyperacidity nor dyspepsia. Conclusions Netazepide suppressed pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. The reduction in basal acid secretion and greater increase in serum gastrin by the combination is consistent with more effective acid suppression. Despite our failure to show rabeprazole-induced ECL cell hyperplasia and rebound hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a potential treatment for the trophic effects of hypergastrinaemia and, with or without a PPI, is a potential treatment for acid-related conditions. PMID:25335860

  3. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

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

    2014-01-01

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

  4. Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer.

    PubMed

    Arrieta, Oscar; Villarreal-Garza, Cynthia; Vizcaíno, Gloria; Pineda, Benjamín; Hernández-Pedro, Norma; Guevara-Salazar, Patricia; Wegman-Ostrosky, Talia; Villanueva-Rodríguez, Geraldine; Gamboa-Domínguez, Armando

    2015-07-01

    Angiotensin II (ANGII) has been associated with vascular proliferation in tumor and non-tumor models through its receptors AT1 and AT2. Our objective was to determine AT1 and AT2 receptor expression in operable breast cancer and its association with tumor grade, vascular density, and cellular proliferation. Seventy-seven surgically malignant breast tumors with no distant metastasis were included, and 7 benign lesions were used as controls. AT1 and AT2 receptor expression was determined by RT-PCR and immunohistochemistry (IHC) in 68 out of the 77 malignant lesions and in the 7 benign lesions. AT1 and AT2 receptor expression was detected in 35.3 and 25 % of cases, in both RT-PCR and IHC. Tumors that express AT1 showed an increase in T3 stage (92.3 vs. 7.7 % p < 0.001), mitotic index (4 ± 1 vs 2 ± 1, p = 0.05), vascular density (15 ± 3 vs 8 ± 5, p = 0.05), and cellular proliferation (85 ± 18 vs 55 ± 10, p = 0.01) versus AT1-negative lesions. Non-differences between clinical-pathologic variables and AT2 expression were found. AT1 receptor expression was associated to enhance angiogenesis and cellular proliferation rate, but no relationship with AT2 was found. ANGII and its peptides might play a role in the development and pathophysiology of breast cancer, and this could be valuable in the in the development of targeted therapies. PMID:25682288

  5. Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors.

    PubMed

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; de Krijger, Ronald R; Waaijers, Marlijn; Mooij, Diana M; van Koetsveld, Peter M; Barreca, Antonina; De Caro, Maria Laura del Basso; Lombardi, Gaetano; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2004-09-01

    Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2

  6. ΔPK oncolytic activity includes modulation of the tumour cell milieu.

    PubMed

    Bollino, Dominique; Colunga, Aric; Li, Baiquan; Aurelian, Laure

    2016-02-01

    Oncolytic virotherapy is a unique cancer therapeutic that encompasses tumour cell lysis through both virus replication and programmed cell death (PCD) pathways. Nonetheless, clinical efficacy is relatively modest, likely related to the immunosuppressive tumour milieu. Our studies use the herpes simplex virus type 2 (HSV-2)-based oncolytic virus ΔPK that has documented anti-tumour activity associated with virus replication, PCD and cancer stem cell lysis. They are designed to examine whether ΔPK-mediated oncolysis includes the ability to reverse the immunosuppressive tumour microenvironment by altering the balance of cytokines directly secreted by the melanoma cells and to define its mechanism. Here, we show that melanoma cells secreted the immunosuppressive cytokine IL-10, and that secretion was inhibited by ΔPK through virus replication and c-Jun N-terminal kinase/c-Jun activation. ΔPK-induced IL-10 inhibition upregulated surface expression of MHC class I chain-related protein A, the ligand for the activating NKG2D receptor expressed on NK- and cytotoxic T-cells. Concomitantly, ΔPK also upregulated the secretion of inflammatory cytokines TNF-α, granulocyte macrophage colony-stimulating factor and IL-1β through autophagy-mediated activation of Toll-like receptor 2 pathways and pyroptosis, and it inhibited the expression of the negative immune checkpoint regulator cytotoxic T-lymphocyte antigen 4. Pharmacologic inhibition of these processes significantly reduces the oncolytic activity of ΔPK. PMID:26602205

  7. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET

    PubMed Central

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-01-01

    Abstract Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs. All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed. Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0–38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors. Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs. PMID:27149478

  8. Neural endocannabinoid CB1 receptor expression, social status, and behavior in male European starlings.

    PubMed

    DeVries, M Susan; Cordes, Melissa A; Rodriguez, Jonathan D; Stevenson, Sharon A; Riters, Lauren V

    2016-08-01

    Many species modify behavior in response to changes in resource availability or social status; however, the neural mechanisms underlying these modifications are not well understood. Prior work in male starlings demonstrates that status-appropriate changes in behavior involve brain regions that regulate social behavior and vocal production. Endocannabinoids are ubiquitously distributed neuromodulators that are proposed to play a role in adjusting behavior to match social status. As an initial step to provide insight into this hypothesis we observed flocks of male starlings in outdoor aviaries during the breeding season. We used quantitative real-time PCR to measure expression of endocannabinoid CB1 receptors in brain regions involved in social behavior and motivation (lateral septum [LS], ventral tegmental area [VTA], medial preoptic nucleus [POM]) and vocal behavior (Area X and robust nucleus of the arcopallium; RA). Males with nesting sites sang to females and displaced other males more than males without nesting sites. They also had higher levels of CB1 receptor expression in LS and RA. CB1 expression in LS correlated positively with agonistic behaviors. CB1 expression in RA correlated positively with singing behavior. CB1 in VTA also correlated positively with singing when only singing birds were considered. These correlations nicely map onto the well-established role of LS in agonistic behavior and the known role of RA in song production and VTA in motivation and song production. Studies are now needed to precisely characterize the role of CB1 receptors in these regions in the production of status-appropriate social behaviors. PMID:27206544

  9. Chicken TREM-B1, an Inhibitory Ig-Like Receptor Expressed on Chicken Thrombocytes.

    PubMed

    Turowski, Vanessa; Sperling, Beatrice; Hanczaruk, Matthias A; Göbel, Thomas W; Viertlboeck, Birgit C

    2016-01-01

    Triggering receptors expressed on myeloid cells (TREM) form a multigene family of immunoregulatory Ig-like receptors and play important roles in the regulation of innate and adaptive immunity. In chickens, three members of the TREM family have been identified on chromosome 26. One of them is TREM-B1 which possesses two V-set Ig-domains, an uncharged transmembrane region and a long cytoplasmic tail with one ITSM and two ITIMs indicating an inhibitory function. We generated specific monoclonal antibodies by immunizing a Balb/c mouse with a TREM-B1-FLAG transfected BWZ.36 cell line and tested the hybridoma supernatants on TREM-B1-FLAG transfected 2D8 cells. We obtained two different antibodies specific for TREM-B1, mab 7E8 (mouse IgG1) and mab 1E9 (mouse IgG2a) which were used for cell surface staining. Single and double staining of different tissues, including whole blood preparations, revealed expression on thrombocytes. Next we investigated the biochemical properties of TREM-B1 by using the specific mab 1E9 for immunoprecipitation of either lysates of surface biotinylated peripheral blood cells or stably transfected 2D8 cells. Staining with streptavidin coupled horse radish peroxidase revealed a glycosylated monomeric protein of about 50 kDa. Furthermore we used the stably transfected 2D8 cell line for analyzing the cytoplasmic tyrosine based signaling motifs. After pervanadate treatment, we detected phosphorylation of the tyrosine residues and subsequent recruitment of the tyrosine specific protein phosphatase SHP-2, indicating an inhibitory potential for TREM-B1. We also showed the inhibitory effect of TREM-B1 in chicken thrombocytes using a CD107 degranulation assay. Crosslinking of TREM-B1 on activated primary thrombocytes resulted in decreased CD107 surface expression of about 50-70%. PMID:26967520

  10. Characterization of a thyroid hormone receptor expressed in human kidney and other tissues

    SciTech Connect

    Nakai, A.; Seino, S.; Sakurai, A.; Szilak, I.; Bell, G.I.; DeGroot, L.J.

    1988-04-01

    A cDNA encoding a specific form of thyroid hormone receptor expressed in human liver, kidney, placenta, and brain was isolated from a human kidney library. Identical clones were found in human placenta and HepG2 cDNA libraries. The cDNA encodes a 490-amino acid protein. When expressed and translated in vitro, the protein products binds triiodothyronine with K/sub a/ of 2.3 /times/ 10/sup 9/ M/sup /minus/1/. This protein, designated human thyroid hormone receptor type ..cap alpha..2 (hTR..cap alpha..2), has the same domain structure as other members of the v-erbA-related superfamily of receptor genes. It is similar to thyroid hormone receptor type ..cap alpha.. described in chicken and rat and less similar to human thyroid hormone receptor type ..beta.. (formerly referred to as c-erbA..beta..) from placenta. However, it is distinguished from these receptors by an extension of the C-terminal hormone binding domain making it 80 amino acids longer than rat thyroid hormone receptor type ..cap alpha..1. Different sizes of mRNA found in liver and kidney suggest that there may be tissue-specific processing of the primary transcript of this gene. Identification of human thyroid hormone receptor type ..cap alpha..2 indicates that two or more forms of thyroid hormone receptor exist in human tissues and may explain the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in the thyroid hormone resistance syndromes.

  11. Characteristics of glycine receptors expressed by embryonic rat brain mRNAs.

    PubMed

    García-Alcocer, G; García-Colunga, J; Martínez-Torres, A; Miledi, R

    2001-02-27

    A study was made of glycine (Gly) and gamma-aminobutyric acid (GABA) receptors expressed in Xenopus oocytes injected with rat mRNAs isolated from the encephalon, midbrain, and brainstem of 18-day-old rat embryos. In oocytes injected with encephalon, midbrain, or brainstem mRNAs, the Gly-current amplitudes (membrane current elicited by Gly; 1 mM Gly) were respectively 115 +/- 35, 346 +/- 28, and 389 +/- 22 nA, whereas the GABA-currents (1 mM GABA) were all < or =40 nA. Moreover, the Gly-currents desensitized faster in oocytes injected with encephalon or brainstem mRNAs. The EC(50) for Gly was 611 +/- 77 microM for encephalon, 661 +/- 28 microM for midbrain, and 506 +/- 18 microM for brainstem mRNA-injected oocytes, and the corresponding Hill coefficients were all approximately 2. Strychnine inhibited all of the Gly-currents, with an IC(50) of 56 +/- 3 nM for encephalon, 97 +/- 4 nM for midbrain, and 72 +/- 4 nM for brainstem mRNAs. During repetitive Gly applications, the Gly-currents were potentiated by 1.6-fold for encephalon, 2.1-fold for midbrain, and 1.3-fold for brainstem RNA-injected oocytes. Raising the extracellular Ca(2+) concentration significantly increased the Gly-currents in oocytes injected with midbrain and brainstem mRNAs. Reverse transcription-PCR studies showed differences in the Gly receptor (GlyR) alpha-subunits expressed, whereas the beta-subunit was present in all three types of mRNA. These results indicate differential expression of GlyR mRNAs in the brain areas examined, and these mRNAs lead to the expression of GlyRs that have different properties. The modulation of GlyRs by Ca(2+) could play important functions during brain development. PMID:11226317

  12. High Cell Surface Death Receptor Expression Determines Type I Versus Type II Signaling*

    PubMed Central

    Meng, Xue Wei; Peterson, Kevin L.; Dai, Haiming; Schneider, Paula; Lee, Sun-Hee; Zhang, Jin-San; Koenig, Alexander; Bronk, Steve; Billadeau, Daniel D.; Gores, Gregory J.; Kaufmann, Scott H.

    2011-01-01

    Previous studies have suggested that there are two signaling pathways leading from ligation of the Fas receptor to induction of apoptosis. Type I signaling involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to amplify a more modest death receptor-initiated signal. The biochemical basis for this dichotomy has previously been unclear. Here we show that type I cells have a longer half-life for Fas message and express higher amounts of cell surface Fas, explaining the increased recruitment of FADD and subsequent signaling. Moreover, we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can signal through a type I pathway upon forced receptor overexpression and that shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to type II signaling. Importantly, the same cells can exhibit type I signaling for Fas and type II signaling for TRAIL (TNF-α-related apoptosis-inducing ligand), indicating that the choice of signaling pathway is related to the specific receptor, not some other cellular feature. Additional experiments revealed that up-regulation of cell surface death receptor 5 levels by treatment with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells from type II to type I. Collectively, these results suggest that the type I/type II dichotomy reflects differences in cell surface death receptor expression. PMID:21865165

  13. The adaptor 3BP2 is required for KIT receptor expression and human mast cell survival

    PubMed Central

    Ainsua-Enrich, Erola; Serrano-Candelas, Eva; Álvarez-Errico, Damiana; Picado, César; Sayós, Joan; Rivera, Juan; Martín, Margarita

    2015-01-01

    3BP2 is a cytoplasmic adaptor protein that acts as a positive regulator in mast cell FcεRI-dependent signaling. The KIT receptor whose ligand is the stem cell factor (SCF) is necessary for mast cell development, proliferation and survival as well as for optimal IgE-dependent signal. Activating mutations in KIT have been associated with several diseases including mastocytosis. In the present work, we found that 3BP2 silencing impairs KIT signaling pathways, thus affecting PI3K and MAP kinase pathways in human mast cells from HMC-1, LAD2 (human mast cell lines) and CD34+-derived mast cells. Unexpectedly, silencing of 3BP2 reduces KIT expression in normal human mast cells as well as in HMC-1 cells where KIT is mutated, thus increasing cellular apoptosis and caspase 3/7 activity. 3BP2 silencing reduces KIT transcription expression levels. Interestingly, 3BP2 silencing decreased MITF expression, a transcription factor involved in KIT expression. Reconstitution of 3BP2 in knockdown cells leads to reversal of KIT expression as well as survival phenotype. Accordingly MITF reconstitution enhances KIT expression levels in 3BP2 silenced cells. Moreover, downregulation of KIT expression by miRNA221 overexpression or the proteasome inhibitor bortezomib also reduced 3BP2 and MITF expression. Furthermore, KIT tyrosine activity inhibition reduced 3BP2 and MITF expression, demonstrating again a tight and reciprocal relationship between these molecules. Taken together, our results show that 3BP2 regulates human mast cell survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression, suggesting its potential as a therapeutic target in mast cell-mediated inflammatory diseases and deregulated KIT disorders. PMID:25810396

  14. Lipid flippase modulates olfactory receptor expression and odorant sensitivity in Drosophila

    PubMed Central

    Ha, Tal Soo; Xia, Ruohan; Zhang, Haiying; Smith, Dean P.

    2014-01-01

    In Drosophila melanogaster, the male-specific pheromone cVA (11-cis-vaccenyl acetate) functions as a sex-specific social cue. However, our understanding of the molecular mechanisms underlying cVA pheromone transduction and its regulation are incomplete. Using a genetic screen combined with an electrophysiological assay to monitor pheromone-evoked activity in the cVA-sensing Or67d neurons, we identified an olfactory sensitivity factor encoded by the dATP8B gene, the Drosophila homolog of mammalian ATP8B. dATP8B is expressed in all olfactory neurons that express Orco, the odorant receptor coreceptor, and the odorant responses in most Orco-expressing neurons are reduced. Or67d neurons are severely affected, with strongly impaired cVA-induced responses and lacking spontaneous spiking in the mutants. The dATP8B locus encodes a member of the P4-type ATPase family thought to flip aminophospholipids such as phosphatidylserine and phosphatidylethanolamine from one membrane leaflet to the other. dATP8B protein is concentrated in the cilia of olfactory neuron dendrites, the site of odorant transduction. Focusing on Or67d neuron function, we show that Or67d receptors are mislocalized in dATP8B mutants and that cVA responses can be restored to dATP8B mutants by misexpressing a wild-type dATP8B rescuing transgene, by expressing a vertebrate P4-type ATPase member in the pheromone-sensing neurons or by overexpressing Or67d receptor subunits. These findings reveal an unexpected role for lipid translocation in olfactory receptor expression and sensitivity to volatile odorants. PMID:24821794

  15. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas. PMID:24287797

  16. Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis

    PubMed Central

    Weehuizen, Tassili A. F.; Hommes, Tijmen J.; Lankelma, Jacqueline M.; de Jong, Hanna K.; Roelofs, Joris. J.T.H.; de Vos, Alex F.; Colonna, Marco; van der Poll, Tom; Wiersinga, W. Joost

    2016-01-01

    Background Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis. We aimed to characterize the expression and function of TREM-1 and TREM-2 in melioidosis. Methodology/Principal Findings Wild-type, TREM-1/3 (Trem-1/3-/-) and TREM-2 (Trem-2-/-) deficient mice were intranasally infected with live B. pseudomallei and killed after 24, and/or 72 h for the harvesting of lungs, liver, spleen, and blood. Additionally, survival studies were performed. Cellular functions were further analyzed by stimulation and/or infection of isolated cells. TREM-1 and TREM-2 expression was increased both in the lung and liver of B. pseudomallei-infected mice. Strikingly, Trem-2-/-, but not Trem-1/3-/-, mice displayed a markedly improved host defense as reflected by a strong survival advantage together with decreased bacterial loads, less inflammation and reduced organ injury. Cellular responsiveness of TREM-2, but not TREM-1, deficient blood and bone-marrow derived macrophages (BMDM) was diminished upon exposure to B. pseudomallei. Phagocytosis and intracellular killing of B. pseudomallei by BMDM and alveolar macrophages were TREM-1 and TREM-2-independent. Conclusions/Significance We found that TREM-2, and to a lesser extent TREM-1, plays a remarkable detrimental role in the host defense against a clinically relevant Gram-negative pathogen in mice: TREM-2 deficiency restricts the inflammatory response, thereby decreasing organ damage and mortality. PMID:27253382

  17. Chicken TREM-B1, an Inhibitory Ig-Like Receptor Expressed on Chicken Thrombocytes

    PubMed Central

    Turowski, Vanessa; Sperling, Beatrice; Hanczaruk, Matthias A.; Göbel, Thomas W.; Viertlboeck, Birgit C.

    2016-01-01

    Triggering receptors expressed on myeloid cells (TREM) form a multigene family of immunoregulatory Ig-like receptors and play important roles in the regulation of innate and adaptive immunity. In chickens, three members of the TREM family have been identified on chromosome 26. One of them is TREM-B1 which possesses two V-set Ig-domains, an uncharged transmembrane region and a long cytoplasmic tail with one ITSM and two ITIMs indicating an inhibitory function. We generated specific monoclonal antibodies by immunizing a Balb/c mouse with a TREM-B1-FLAG transfected BWZ.36 cell line and tested the hybridoma supernatants on TREM-B1-FLAG transfected 2D8 cells. We obtained two different antibodies specific for TREM-B1, mab 7E8 (mouse IgG1) and mab 1E9 (mouse IgG2a) which were used for cell surface staining. Single and double staining of different tissues, including whole blood preparations, revealed expression on thrombocytes. Next we investigated the biochemical properties of TREM-B1 by using the specific mab 1E9 for immunoprecipitation of either lysates of surface biotinylated peripheral blood cells or stably transfected 2D8 cells. Staining with streptavidin coupled horse radish peroxidase revealed a glycosylated monomeric protein of about 50 kDa. Furthermore we used the stably transfected 2D8 cell line for analyzing the cytoplasmic tyrosine based signaling motifs. After pervanadate treatment, we detected phosphorylation of the tyrosine residues and subsequent recruitment of the tyrosine specific protein phosphatase SHP-2, indicating an inhibitory potential for TREM-B1. We also showed the inhibitory effect of TREM-B1 in chicken thrombocytes using a CD107 degranulation assay. Crosslinking of TREM-B1 on activated primary thrombocytes resulted in decreased CD107 surface expression of about 50–70%. PMID:26967520

  18. Differential effects of diazepam treatment and withdrawal on recombinant GABAA receptor expression and functional coupling.

    PubMed

    Svob Strac, Dubravka; Vlainić, Josipa; Jazvinsćak Jembrek, Maja; Pericić, Danka

    2008-12-30

    Prolonged exposure to benzodiazepines, drugs known to produce tolerance and dependence and also to be abused, leads to adaptive changes in GABA(A) receptors. To further explore the mechanisms responsible for these phenomena, we studied the effects of prolonged diazepam treatment on the recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors, stably expressed in human embryonic kidney (HEK) 293 cells. The results demonstrating that long-term (48 and 72 h) exposure of cells to a high concentration of diazepam (50 microM) enhanced the maximum number (B(max)) of [(3)H]flunitrazepam, [(3)H]muscimol and [(3)H]t-butylbicycloorthobenzoate ([(3)H]TBOB) binding sites, without changing their affinity (K(d)), suggested the up-regulation of GABA(A) receptors. As demonstrated by cell counting and WST-1 proliferation assay, the observed increase in receptor expression was not a consequence of stimulated growth of cells exposed to diazepam. Semi-quantitative RT-PCR and Western blot analysis, showing elevated levels of alpha(1) subunit mRNA as well as beta(2) and gamma(2) subunit proteins, respectively, suggested that prolonged high dose diazepam treatment induced de novo receptor synthesis by acting at both transcriptional and translational levels. The finding that the number of GABA(A) receptor binding sites returned to control value 24 h following diazepam withdrawal, makes this process less likely to account for the development of benzodiazepine tolerance and dependence. On the other hand, the results demonstrating that observed functional uncoupling between GABA and benzodiazepine binding sites persisted after the termination of diazepam treatment supported the hypothesis of its possible role in these phenomena. PMID:18955034

  19. Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection.

    PubMed

    Bandaru, Anuradha; Devalraju, Kamakshi P; Paidipally, Padmaja; Dhiman, Rohan; Venkatasubramanian, Sambasivan; Barnes, Peter F; Vankayalapati, Ramakrishna; Valluri, Vijayalakshmi

    2014-07-01

    We studied the factors that regulate IL-23 receptor expression and IL-17 production in human tuberculosis infection. Mycobacterium tuberculosis (M. tb)-stimulated CD4(+) T cells from tuberculosis patients secreted less IL-17 than did CD4(+) T cells from healthy tuberculin reactors (PPD(+) ). M. tb-cultured monocytes from tuberculosis patients and PPD(+) donors expressed equal amounts of IL-23p19 mRNA and protein, suggesting that reduced IL-23 production is not responsible for decreased IL-17 production by tuberculosis patients. Freshly isolated and M. tb-stimulated CD4(+) T cells from tuberculosis patients had reduced IL-23 receptor and phosphorylated STAT3 (pSTAT3) expression, compared with cells from PPD(+) donors. STAT3 siRNA reduced IL-23 receptor expression and IL-17 production by CD4(+) T cells from PPD(+) donors. Tuberculosis patients had increased numbers of PD-1(+) T cells compared with healthy PPD(+) individuals. Anti-PD-1 antibody enhanced pSTAT3 and IL-23R expression and IL-17 production by M. tb-cultured CD4(+) T cells of tuberculosis patients. Anti-tuberculosis therapy decreased PD-1 expression, increased IL-17 and IFN-γ production and pSTAT3 and IL-23R expression. These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduce IL-23 receptor expression and IL-17 production by CD4(+) T cells of tuberculosis patients. PMID:24643836

  20. Androgen receptor expression and morphology of forebrain and neuromuscular systems in male green anoles displaying individual differences in sexual behavior.

    PubMed

    Neal, Jennifer K; Wade, Juli

    2007-08-01

    Investigating individual differences in sexual performance in unmanipulated males is important for understanding natural relationships between behavior and morphology, and the mechanisms regulating them. Among male green anole lizards, some court and copulate frequently (studs) and others do not (duds). To evaluate potential factors underlying differences in the level of these behaviors, morphology and androgen receptor expression in neuromuscular courtship and copulatory structures, as well as in the preoptic area and amygdala, were compared in males displaying varying degrees of sexual function. This study revealed that individual differences in behavior among unmanipulated males, in particular the extension of a throat fan (dewlap) used during courtship, were positively correlated with the size of fibers in the associated muscle and with soma size in the amygdala. The physiological response to testosterone, as indicated by the height of cells in an androgen-sensitive portion of the kidney, was also correlated with male sexual behavior, and predicted it better than plasma androgen levels. Androgen receptor expression was not related to the display of courtship or copulation in any of the tissues examined. The present data indicate that higher levels of male courtship behavior result in (or are the result of) enhanced courtship muscle and amygdala morphology, and that androgen-sensitive tissue in studs may be more responsive to testosterone than duds. However, some mechanism(s) other than androgen receptor expression likely confer this difference in responsiveness. PMID:17531996

  1. Androgen receptor expression and morphology of forebrain and neuromuscular systems in male green anoles displaying individual differences in sexual behavior

    PubMed Central

    Neal, Jennifer K.; Wade, Juli

    2010-01-01

    Investigating individual differences in sexual performance in unmanipulated males is important for understanding natural relationships between behavior and morphology, and the mechanisms regulating them. Among male green anole lizards, some court and copulate frequently (studs) and others do not (duds). To evaluate potential factors underlying differences in the level of these behaviors, morphology and androgen receptor expression in neuromuscular courtship and copulatory structures, as well as in the preoptic area and amygdala, were compared in males displaying varying degrees of sexual function. This study revealed that individual differences in behavior among unmanipulated males, in particular the extension of a throat fan (dewlap) used during courtship, were positively correlated with the size of fibers in the associated muscle and with soma size in the amygdala. The physiological response to testosterone, as indicated by the height of cells in an androgen-sensitive portion of the kidney, was also correlated with male sexual behavior, and predicted it better than plasma androgen levels. Androgen receptor expression was not related to the display of courtship or copulation in any of the tissues examined. The present data indicate that higher levels of male courtship behavior result in (or are the result of) enhanced courtship muscle and amygdala morphology, and that androgen-sensitive tissue in studs may be more responsive to testosterone than duds. However, some mechanism(s) other than androgen receptor expression likely confer this difference in responsiveness. PMID:17531996

  2. Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux, plasma motilin and serum gastrin

    PubMed Central

    Zhang, Zhen-Hai; Wu, Shuo-Dong; Wang, Bing; Su, Yang; Jin, Jun-Zhe; Kong, Jing; Wang, Hao-Lin

    2008-01-01

    AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by measuring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoassay. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the control group (t = 5.254, 3.438 and 3.527, P < 0.001). SOD of the reflux group was shorter than the control group (t = 2.049, P < 0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t = -2.230 and -2.235, P < 0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastrointestinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi

  3. Epidermal growth factor receptor expression in primary cultured human colorectal carcinoma cells.

    PubMed Central

    Tong, W. M.; Ellinger, A.; Sheinin, Y.; Cross, H. S.

    1998-01-01

    In situ hybridization on human colon tissue demonstrates that epidermal growth factor receptor (EGFR) mRNA expression is strongly increased during tumour progression. To obtain test systems to evaluate the relevance of growth factor action during carcinogenesis, primary cultures from human colorectal carcinomas were established. EGFR distribution was determined in 2 of the 27 primary cultures and was compared with that in well-defined subclones derived from the Caco-2 cell line, which has the unique property to differentiate spontaneously in vitro in a manner similar to normal enterocytes. The primary carcinoma-derived cells had up to three-fold higher total EGFR levels than the Caco-2 subclones and a basal mitotic rate at least fourfold higher. The EGFR affinity constant is 0.26 nmol l(-1), which is similar to that reported in Caco-2 cells. The proliferation rate of Caco-2 cells is mainly induced by EGF from the basolateral cell surface where the majority of receptors are located, whereas primary cultures are strongly stimulated from the apical side also. This corresponds to a three- to fivefold higher level of EGFR at the apical cell surface. This redistribution of EGFR to apical plasma membranes in advanced colon carcinoma cells suggests that autocrine growth factors in the colon lumen may play a significant role during tumour progression. Images Figure 1 Figure 2 PMID:9667648

  4. Developmental regulation of voltage-gated K+ channel and GABAA receptor expression in Bergmann glial cells.

    PubMed

    Müller, T; Fritschy, J M; Grosche, J; Pratt, G D; Möhler, H; Kettenmann, H

    1994-05-01

    , although they yield a prominent staining of both the Purkinje cells and the granule cells. These changes in the Bergmann glial cell membrane properties and GABAA receptor expression suggest a transition between functional states during development of the Bergmann glial cells. PMID:8182424

  5. Protein malnutrition up-regulates growth hormone receptor expression in rat splenic B lymphocytes.

    PubMed

    Mejía-Naranjo, Wilson; Sánchez-Gomez, Myriam

    2004-12-01

    The reciprocal interaction between the endocrine and immune systems has been the subject of active research during the last decade, and an important body of evidence has accumulated supporting the role of the GH/IGF axis in immune function. More recently, the GH/IGF axis has been postulated as playing an important role in the modulation of stress conditions, such as catabolic stages, aging-related disorders, immunodeficient aids patients and malnutrition. Whether these effects are exerted through endocrine, autocrine or paracrine mechanisms remains to be determined for different immune cell types and tissues. The aim of the current study was to define which specific subsets of lymphocytes are the primary targets for GH action. In addition, the regulatory role of stress induced by protein restriction was investigated with respect to the relative distribution of GH receptor positive lymphoid cells. Normal growing rats were fed isocaloric diets with variable protein content (0, 4, 8, 12 and 20%) for a period of 14 days. The lymphoid cells were then separated from spleen, lymph nodes and peripheral blood lymphocytes. Flow cytometry analysis measured the binding characteristics of Fluos-rrGH to lymphocytes together with specific PE-labelled mAbs defining CD4+ and CD8+ T cells and B lymphocytes. The pattern of expression of the GH receptor differed among the lymphoid tissues and cell subsets. Spleen was the most responsive organ to protein deprivation with highest GH receptor expression in B lymphocytes, followed by CD4+ T cells. As the protein intake was decreased from 20% to 0%, the percentage of GHR positive cells increased from 12% to 52% in splenic B lymphocytes and from 8% to 17% in CD4+ T cells. In contrast, only 10%-13% of lymphocytes in lymph nodes and 2%-4% in circulation, showed binding sites to GH associated with protein deprivation. In conclusion, the increase in GH receptors on lymphocytes under catabolic stress induced by protein malnutrition gives support

  6. Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

    PubMed

    Mamo, J C; Watts, G F; Barrett, P H; Smith, D; James, A P; Pal, S

    2001-09-01

    Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plasma apolipoprotein B(48) (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB(48) was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB(48) and RP curves (IAUC) were both significantly greater in obese subjects (apoB(48): 97 +/- 17 vs. 44 +/- 12 microg.ml(-1). h; RP: 3,120 +/- 511 vs. 1,308 +/- 177 U. ml(-1). h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM. h, P < 0.06). Moreover, peak postprandial triglyceride was delayed by approximately 2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/microg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic

  7. The Gastrin-Releasing Peptide Receptor (GRPR) in the Spinal Cord as a Novel Pharmacological Target

    PubMed Central

    Takanami, Keiko; Sakamoto, Hirotaka

    2014-01-01

    Gastrin-releasing peptide (GRP) is a mammalian neuropeptide that acts through the G protein-coupled receptor, GRP receptor (GRPR). Increasing evidence indicates that GRPR-mediated signaling in the central nervous system plays an important role in many physiological processes in mammals. Additionally, we have recently reported that the GRP system within the lumbosacral spinal cord not only controls erection but also triggers ejaculation in male rats. This system of GRP neurons is sexually dimorphic, being prominent in male rats but vestigial or absent in females. It is suggested that the sexually dimorphic GRP/GRPR system in the lumbosacral spinal cord plays a critical role in the regulation of male sexual function. In parallel, it has been reported that the somatosensory GRP/GRPR system in the spinal cord contributes to the regulation of itch specific transmission independently of the pain transmission. Interestingly, these two distinct functions in the same spinal region are both regulated by the neuropeptide, GRP. In this report, we review findings on recently identified GRP/GRPR systems in the spinal cord. These GRP/GRPR systems in the spinal cord provide new insights into pharmacological treatments for psychogenic erectile dysfunction as well as for chronic pruritus. PMID:25426011

  8. Antiulcerogenic activity of Alchornea castaneaefolia: effects on somatostatin, gastrin and prostaglandin.

    PubMed

    Hiruma-Lima, Clélia Akiko; Calvo, Tamara Roberta; Rodrigues, Clenilson Martins; Andrade, Fábio Donizete Pezzuto; Vilegas, Wagner; Brito, Alba Regina Monteiro Souza

    2006-03-01

    The hydroethanolic extract of the leaves (HEL) and bark (HEB) obtained from Alchornea castaneaefolia (Euphorbiaceae) were investigated for their ability to prevent ulceration of the gastric mucosa in animal models. HEL (500 and 1000 mg/kg) and HEB (1000 mg/kg) significantly reduced the gastric injuries induced by the combination of HCl/ethanol and lowered the severity of gastric damage formation induced by indomethacin/bethanechol in mice. Further investigation showed that HEL also inhibited formation of ulcers in mice submitted to stress and pylorus ligature, but HEL did not modify gastric juice parameters in Shay mice. HEL was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats. An enriched flavonoidic fraction (EFF at dose of 100mg/kg) obtained from HEL reduced gastric lesions induced by HCl/ethanol and indomethacin/bethanechol in mice. Although EFF did not modify the amount of free mucus production by gastric mucosa, it was able to increase prostaglandin production. When administered to rats submitted to ethanol-induced gastric lesions, EFF increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. Phytochemical investigation on HEL and EFF led to the isolation of flavonoids glycosides as the main compounds, thus suggesting that these substances may be involved in the observed antiulcer activity. PMID:16253451

  9. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis: A Meta-Analysis.

    PubMed

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-05-01

    A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG).An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs).Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45-0.51) and 0.79 (95% CI: 0.77-0.81), respectively. The DOR was 5.93 (95% CI: 2.93-11.99), and the AUC was 0.82.G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future. PMID:27149493

  10. Gastrin Releasing Peptide Modulates Fast Delayed Rectifier Potassium Current in Per1-Expressing SCN Neurons

    PubMed Central

    Gamble, Karen L.; Kudo, Takashi; Colwell, Christopher S.; McMahon, Douglas G.

    2011-01-01

    The mammalian circadian clock in the suprachiasmatic nucleus (SCN) drives and maintains 24-h physiological rhythms, the phases of which are set by the local environmental light-dark cycle. Gastrin releasing peptide (GRP) communicates photic phase setting signals in the SCN by increasing neurophysiological activity of SCN neurons. Here, the ionic basis for persistent GRP-induced changes in neuronal activity was investigated in SCN slice cultures from Per1::GFP reporter mice during the early night. Recordings from Per1-fluorescent neurons in SCN slices several hours after GRP treatment revealed a significantly greater action potential frequency, a significant increase in voltage-activated outward current at depolarized potentials, and a significant increase in 4-aminopyridine (4-AP) sensitive fast delayed rectifier (fDR) potassium currents when compared to vehicle-treated slices. In addition, the persistent increase in spike rate following early night GRP application was blocked in SCN neurons from mice deficient in Kv3 channel proteins. Because fDR currents are regulated by the clock and are elevated in amplitude during the day, the present results support the model that GRP delays the phase of the clock during the early night by prolonging day-like membrane properties of SCN cells. Furthermore, these findings implicate fDR currents in the ionic basis for GRP-mediated entrainment of the primary mammalian circadian pacemaker. PMID:21454290

  11. An update of radiolabeled bombesin analogs for gastrin-releasing peptide receptor targeting.

    PubMed

    Yu, Zilin; Ananias, Hildo J K; Carlucci, Giuseppe; Hoving, Hilde D; Helfrich, Wijnand; Dierckx, Rudi A J O; Wang, Fan; de Jong, Igle J; Elsinga, Philip H

    2013-01-01

    Prostate cancer is a critical public health problem in USA and Europe. New non-invasive imaging methods are urgently needed, due to the low accuracy and specificity of current screen methods and the desire of localizing primary prostate cancer and bone metastasis. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are the non-invasive and sensitive imaging methods which have been widely used for diagnosing diseases in the clinic. Lack of suitable radiotracers is the major issue for nuclear imaging of prostate cancer, although radiolabeled bombesin (BN) peptides targeting the Gastrin-Releasing Peptide Receptor (GRPR) on tumor cells are widely investigated. In this review we discuss the recent trends in the development of GRPR-targeted radiopharmaceuticals based on BN analogs with regard to their potential for imaging and therapy of GRPR-expressing malignancies. Following a brief introduction of GRPR and bombesin peptides, we summarize the properties of prostate cancer specific radiolabeled bombesins. New bombesin tracers published in the last five years are reviewed and compared according to their novelties in biomolecules, radionuclides, labeling methods, bifunctional chelators and linkers. Hot topics such as multimerization, application of agonists and antagonists are highlighted in the review. Lastly, a few clinical trials of cancer nuclear imaging with radiolabeled bombesin have been discussed. PMID:23431995

  12. Oxygen, Gastrin-Releasing Peptide, and Pediatric Lung Disease: Life in the Balance

    PubMed Central

    Sunday, Mary E.

    2014-01-01

    Excessive oxygen (O2) can cause tissue injury, scarring, aging, and even death. Our laboratory is studying O2-sensing pulmonary neuroendocrine cells (PNECs) and the PNEC-derived product gastrin-releasing peptide (GRP). Reactive oxygen species (ROS) generated from exposure to hyperoxia, ozone, or ionizing radiation (RT) can induce PNEC degranulation and GRP secretion. PNEC degranulation is also induced by hypoxia, and effects of hypoxia are mediated by free radicals. We have determined that excessive GRP leads to lung injury with acute and chronic inflammation, leading to pulmonary fibrosis (PF), triggered via ROS exposure or by directly treating mice with exogenous GRP. In animal models, GRP-blockade abrogates lung injury, inflammation, and fibrosis. The optimal time frame for GRP-blockade and the key target cell types remain to be determined. The concept of GRP as a mediator of ROS-induced tissue damage represents a paradigm shift about how O2 can cause injury, inflammation, and fibrosis. The host PNEC response in vivo may depend on individual ROS sensing mechanisms and subsequent GRP secretion. Ongoing scientific and clinical investigations promise to further clarify the molecular pathways and clinical relevance of GRP in the pathogenesis of diverse pediatric lung diseases. PMID:25101250

  13. Immunoreactive gastrin (IRG) and cholecystokinin (IRCCK) in chickens before and after bombesin (BBS)

    SciTech Connect

    Rayford, P.L.; Inoue, K.; Chowdhury, P.; McKay, D.

    1986-03-01

    This study was conducted in chickens to measure IRG and IRCCK in gut and brain tissues and in plasma before and after stimulation with BBS. After 24 h fast, six chickens were sacrificed and regions of the GI tract, liver, pancreas, and brain were collected, extracted in boiling water or 0.5M acetic acid. Five chickens were infused IV with saline for 30 min. and then with 3 ..mu..g/Kg-hr of BBs for 1 h. Levels of IRG and IRCCK were measured by radioimmunoassays. IRG was 6 pmol/g in the ileum, 3.5 pmol/g in the gizzard and was less in other regions of the GI tract. IRG was 12 pmol/g in cortex, 8 pmol/g in cerebellum and smaller amount in the liver. The amounts of IRCCK measured in all the tissue extracts were in the range of 0.1 to 0.5 pmol/g. The highest concentration was in the duodenum. Before BBS, IRG and IRCCK levels in the plasma were 9 +/- 2, and 81 +/- 24 pmol/g, respectively. After BBS, IRG was 13 +/- 1 and IRCCK was 139 +/- 18 (p < 0.05). Integrated responses for IRG and for IRCCK during BBS were increased significantly above basal. Substances with immunogenic similarities to gastrin and cholecystokinin can be measured in extracts of GI tissues and in plasma of chickens. They can be released into circulation by bombesin.

  14. Acid Secretion and Serum Gastrin Levels in the Zollinger-Ellison Syndrome

    PubMed Central

    Sanchez, R. Edward; Longmire, William P.; Passaro, Edward

    1972-01-01

    Thirteen cases of patients with the Zollinger-Ellison syndrome were reviewed. In two cases the diagnosis was made by incidental biopsy of small liver nodules at operation for peptic ulcer disease. Seven patients had gastric secretory tests which showed a basal acid output to maximum acid output ratio of more than 65 percent. Five patients had bao:mao ratios less than 50 percent. A 30-month interval between incidental discovery of tumor and clinically evident disease was observed in two patients. Recurrence of symptoms after excision of tumor was noted after a similar interval in another case. Serum gastrin levels, before total gastrectomy, were elevated in all cases. The lowest preoperative level in this series of patients was 550 picograms per ml (normal 100 to 150 picograms). They were diagnostic in two patients with normal gastric secretory studies. The levels fell to normal following total gastrectomy in six patients. Two patients still had elevated levels five years and 14 years after total gastrectomy. One was discovered to have a parathyroid adenoma with hypercalcemia. Total gastrectomy was curative in all the patients with the Zollinger-Ellison syndrome; lesser operations were not. ImagesFigure 1.Figure 2.Figure 3.Figure 3.Figure 4. PMID:5031740

  15. Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY.

    PubMed Central

    Goodlad, R A; Lenton, W; Ghatei, M A; Adrian, T E; Bloom, S R; Wright, N A

    1987-01-01

    Refeeding starved rats with a fibre free 'elemental' diet increased crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was seen when inert bulk (kaolin) was added to the 'elemental' diet. Addition of a poorly fermentable dietary 'fibre' (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable 'fibre' (purified wheat bran) caused a large proliferative response in the proximal, mid and distal colon and in the distal small intestine. A gel forming 'fibre' also stimulated proliferation in the distal colon. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus, whilst inert bulk cannot stimulate colonic epithelial cell proliferation, fermentable 'fibre' is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process. PMID:2826311

  16. Gastrin-releasing peptide expression and its effect on the calcification of developing mouse incisor.

    PubMed

    Lee, Dong-Joon; Jin, Chengri; Kim, Eun-Jung; Lee, Jong-Min; Jung, Han-Sung

    2015-09-01

    Gastrin-releasing peptide (GRP) is considered to be one of the cancer growth factors. This peptide's receptor (GRPR) is known as a G protein-coupled receptor, regulating intracellular calcium storage and releasing signals. This study is the first to investigate the function of GRP during mouse incisor development. We hypothesized that GRP is one of the factors that affects the regulation of calcification during tooth development. To verify the expression pattern of GRP, in situ hybridization was processed during incisor development. GRP was expressed at the late bell stage and hard tissue formation stage in the epithelial tissue. To identify the genuine function of GRP during incisor development, a gain-of-function analysis was performed. After GRP overexpression in culture, the phenotype of ameloblasts, odontoblasts and predentin was altered compared to control group. Moreover, enamel and dentin thickness was increased after renal capsule transplantation of GRP-overexpressed incisors. With these results, we suggest that GRP plays a significant role in the formation of enamel and dentin by regulating ameloblasts and predentin formation, respectively. Thus, GRP signaling is strongly related to calcium acquisition and secretion during mouse incisor development. PMID:26126650

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

    PubMed Central

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

    1982-01-01

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

  18. Metabolic reprogramming of the tumour microenvironment.

    PubMed

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

    2015-10-01

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

  19. Recurrent hyperphosphatemic tumoural calcinosis

    PubMed Central

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

    2012-01-01

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

  20. Modulation of gastrin and epidermal growth factor by pyrrolizidine alkaloids obtained from Senecio brasiliensis in acute and chronic induced gastric ulcers.

    PubMed

    Toma, Walber; Trigo, José Roberto; Bensuaski de Paula, Ana Cláudia; Monteiro Souza Brito, Alba Regina

    2004-05-01

    We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis. The PA extract demonstrated significantly activity in both, acute and chronic gastric ulcers on rats. The effects of PA extract were dose dependent. The mechanisms implicated on this activity were evaluated by determination of gastrin plasma levels in rats subjected to the acute treatment with PA extract and by expression of mRNA of Epidermal Growth Factor (EGF) after chronic treatment with this extract. The results showed that the PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF. PMID:15213731

  1. [Drug therapy for neuroendocrine tumours].

    PubMed

    Tóth, Miklós

    2013-09-29

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

  2. Tumours of bones and joints

    PubMed Central

    Misdorp, W.; Van Der Heul, R. O.

    1976-01-01

    Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157

  3. Tumours of the urinary bladder

    PubMed Central

    Pamukcu, A. M.

    1974-01-01

    Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours. Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs—the two species most studied. They are described under the following names: papilloma, adenoma, transitional cell carcinoma (with variants), squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16 PMID:4371741

  4. Distribution of Photofrin between tumour cells and tumour associated macrophages.

    PubMed Central

    Korbelik, M.; Krosl, G.; Olive, P. L.; Chaplin, D. J.

    1991-01-01

    Photofrin levels in cells derived from SCCVII tumours, excised from mice that previously received the drug, were measured using a fluorescence activated cell sorter (FACS). Concomitantly, in the same cells the FACS was used to measure fluorescein isothiocyanate (FITC) fluorescence that originated from FITC-conjugated antimouse IgG added to the cell suspension before sorting. This later measurement enabled discrimination between IgG negative tumour malignant cells and IgG positive host cells (primarily macrophages). In addition, cellular Photofrin content in 'tumour' and 'host' cells sorted by FACS was determined by chemical extraction. The measurements were performed for the time intervals 1-96 h post Photofrin administration. The data showed consistently higher Photofrin levels in the 'host cells', i.e., tumour associated macrophages (TAM), than in 'tumour' cells. On a per cell basis, at any time point studied there was a minimum of 1.7 times more Photofrin in 'host' than in 'tumour cells', while at 4-12 h postadministration, ratios of up to 3.0 times were observed. This corresponds to ratio values greater than 9, when based on Photofrin content per micrograms cell protein. PMID:1832927

  5. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  6. Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development.

    PubMed

    Walton, Noah M; de Koning, Anoek; Xie, Xiuyuan; Shin, Rick; Chen, Qian; Miyake, Shinichi; Tajinda, Katsunori; Gross, Adam K; Kogan, Jeffrey H; Heusner, Carrie L; Tamura, Kouichi; Matsumoto, Mitsuyuki

    2014-09-01

    In the postnatal hippocampus, newly generated neurons contribute to learning and memory. Disruptions in neurogenesis and neuronal development have been linked to cognitive impairment and are implicated in a broad variety of neurological and psychiatric disorders. To identify putative factors involved in this process, we examined hippocampal gene expression alterations in mice possessing a heterozygous knockout of the calcium/calmodulin-dependent protein kinase II alpha heterozygous knockout gene (CaMK2α-hKO), an established model of cognitive impairment that also displays altered neurogenesis and neuronal development. Using this approach, we identified gastrin-releasing peptide (GRP) as the most dysregulated gene. In wild-type mice, GRP labels NeuN-positive neurons, the lone exception being GRP-positive, NeuN-negative cells in the subgranular zone, suggesting GRP expression may be relevant to neurogenesis and/or neuronal development. Using a model of in vitro hippocampal neurogenesis, we determined that GRP signaling is essential for the continued survival and development of newborn neurons, both of which are blocked by transient knockdown of GRP's cognate receptor (GRPR). Furthermore, GRP appears to negatively regulate neurogenesis-associated proliferation in neural stem cells both in vitro and in vivo. Intracerebroventricular infusion of GRP resulted in a decrease in immature neuronal markers, increased cAMP response element-binding protein (CREB) phosphorylation, and decreased neurogenesis. Despite increased levels of GRP mRNA, CaMK2α-hKO mutant mice expressed reduced levels of GRP peptide. This lack of GRP may contribute to the elevated neurogenesis and impaired neuronal development, which are reversed following exogenous GRP infusion. Based on these findings, we hypothesize that GRP modulates neurogenesis and neuronal development and may contribute to hippocampus-associated cognitive impairment. PMID:24806094

  7. Insulinotropic action of bombesin-like peptides mediated by gastrin-releasing peptide receptors in steers.

    PubMed

    Zhao, H Q; Yao, G; Yannaing, S; ThanThan, S; Kuwayama, H

    2016-01-01

    The present study characterizes the receptor that mediates the insulinotropic action of bombesin-like peptides (BLP) in ruminants. Eight Holstein steers were randomly and intravenously injected with synthetic bovine gastrin-releasing peptide (GRP; 0.9 nmol/kg BW), neuromedin B (NMB; 0.9 nmol/kg BW), or neuromedin C (NMC; 0.9 nmol/kg BW), each alone or combined with the antagonist of GRP receptors N-acetyl-GRP-OCHCH (N-GRP-EE; 22.5 nmol/kg BW) or the antagonist of GH secretagogue receptor type 1a (GHS-R1a) [D-Lys]-GHRP-6 (21.5 nmol/kg BW). Blood samples were collected at -10, 0 (just before injection), 5, 10, 15, 20, 30, 45, 60, 75, and 90 min relative to injection time. Levels of injected peptides, insulin, and glucose in plasma were analyzed. Results showed that the peak of insulin levels was seen at 5 min after injection of NMC or GRP. Plasma glucose was observed in 2 phases; a significant rise followed a remarkable fall after NMC or GRP administration compared with injection of the vehicle ( < 0.05). On a same molar basis, effects of GRP on insulin and glucose were more potent than those of NMC ( < 0.05). The NMC-induced changes of insulin and glucose were completely blocked by N-GRP-EE, but [D-Lys]-GHRP-6 did not block any of these changes. Administration of NMB or N-GRP-EE alone did not change the circulating levels of insulin or glucose during any of the sampling time points ( > 0.05). These results indicated that the insulinotropic action of BLP is mediated by GRP receptors but not through a ghrelin/GHS-R1a pathway and that BLP may be involved in the regulation of glucose homeostasis in ruminants. PMID:26812312

  8. Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide, gastrin and cholecystokinin octapeptide

    PubMed Central

    Zhang, Zhen-Hai; Qin, Cheng-Kun; Wu, Shuo-Dong; Xu, Jian; Cui, Xian-Ping; Wang, Zhi-Yi; Xian, Guo-Zhe

    2014-01-01

    AIM: To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups: the control group and pigment stone group. The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice, and were fed a pigment lithogenic diet and sacrificed after 3, 6, 9 and 12 wk. SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage. Serum vasoactive intestinal peptide (VIP), gastrin and cholecystokinin octapeptide (CCK-8) were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay. RESULTS: The incidence of pigment gallstone formation was 0%, 0%, 16.7% and 66.7% in the 3-, 6-, 9- and 12-wk group, respectively. The frequency of myoelectric activity decreased in the 3-wk group. The amplitude of myoelectric activity had a tendency to decrease but not significantly. The frequency of the SO decreased significantly in the 9-wk group. The SO basal pressure and common bile duct pressure increased in the 12-wk group (25.19 ± 7.77 mmHg vs 40.56 ± 11.81 mmHg, 22.35 ± 7.60 mmHg vs 38.51 ± 11.57 mmHg, P < 0.05). Serum VIP was significantly elevated in the 6- and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group. CONCLUSION: Pigment gallstone-causing diet may induce SO dysfunction. The tension of the SO increased. The disturbance in SO motility may play a role in pigment gallstone formation, and changes in serum VIP and CCK-8 may be important causes of SO dysfunction. PMID:24782626

  9. Gastrin releasing peptide-29 requires vagal and splanchnic neurons to evoke satiation and satiety.

    PubMed

    Wright, Susan A; Washington, Martha C; Garcia, Carlos; Sayegh, Ayman I

    2012-01-01

    We have shown that gastrin-releasing peptide-29 (GRP-29), the large molecular form of GRP in rats, reduces meal size (MS, intake of 10% sucrose solution) and prolongs the intermeal interval (IMI). In these studies, we first investigated possible pathways for these responses in rats undergoing total subdiaphragmatic vagotomy (VGX, removal of vagal afferent and efferent innervation of the gut), celiaco-mesenteric ganglionectomy (CMGX, removal of splanchnic afferent and efferent innervation of the gut) and combined VGX and CMGX. Second, we examined if the duodenum communicates the feeding signals (MS and IMI) of GRP-29 (0, 0.3, 1.0, 2.1, 4.1, 10.3 and 17.2 nmol/kg) with the feeding control areas of the hindbrain by performing duodenal myotomy (MYO), a procedure that severs some layers of the duodenal wall including the vagal, splanchnic and enteric neurons. We found that GRP-29 (2.1, 4.1, 10.3, 17.2 nmol/kg) reduced the size of the first meal (10% sucrose) and (1, 4.1, 10.3 nmol/kg) prolongs the first IMI but did not affect the subsequent meals or IMIs. In addition, CMGX and combined VGX/CMGX attenuated reduction of MS by GRP-29 and all surgeries attenuated the prolongation of the IMI. Therefore, reduction of MS and prolongation of IMI by GRP-29 require vagal and splanchnic nerves, and the duodenum is the major conduit that communicates prolongation of IMI by GRP-29 with the brain. PMID:22210008

  10. Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor.

    PubMed Central

    Lebacq-Verheyden, A M; Kasprzyk, P G; Raum, M G; Van Wyke Coelingh, K; Lebacq, J A; Battey, J F

    1988-01-01

    The 27-amino-acid gastrin-releasing peptide (GRP1-27) is a neuropeptide and growth factor that is synthesized by various neural and neuroendocrine cells. The major pro-GRP hormone (isoform I) contains both GRP1-27 and a novel C-terminal extension peptide termed pro-GRP31-125. In order to define potentially active neuropeptides that could be generated from this novel protein domain, we analyzed the posttranslational processing of endogenous human pro-GRP1-125 in a small-cell lung cancer cell line. Because such studies are much easier in an overexpression system, we investigated at the same time the posttranslational processing of baculovirus-expressed human pro-GRP1-125 in an insect ovary cell line. In the small-cell lung cancer cell line, GRP1-27 was cleaved as expected from the endogenous prohormone at a pair of basic amino acids (29 and 30) and alpha-amidated at its C-terminal methionine; however, a number of novel peptides were generated by additional cleavages in the pro-GRP31-125 domain. In the insect ovary cell line, GRP1-27 was cleaved from the expressed prohormone by a different mechanism, as were a number of other peptides that appeared to be similar in size to those produced by the human neuroendocrine tumor cell line. These data show for the first time that an insect ovary cell line that is widely used to overexpress proteins can process a human neuropeptide precursor. They also reveal the existence of novel pro-GRP-derived peptides that are candidates for biologically active ligands. Images PMID:3211139

  11. Specializations of Gastrin Releasing Peptide Cells of the Mouse Suprachiasmatic Nucleus

    PubMed Central

    Drouyer, Elise; LeSauter, Joseph; Hernandez, Amanda L.; Silver, Rae

    2010-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in physiology and behavior. It is constituted of a heterogeneous population of cells which together form the circuits underlying its master clock function. Numerous studies suggest the existence of two regions that have been termed core and shell. At a gross level, differences between these regions map to distinct functional differences, though the specific role(s) of various peptidergic cellular phenotypes remains unknown. In mouse, gastrin releasing peptide (GRP) cells lie in the core, are directly retinorecipient and lack detectable rhythmicity in clock gene expression, raising interest in their role in the SCN. Here, we provide evidence that calbindin expressing cells of perinatal mouse SCN express GRP, identified by a green fluorescent protein (GFP+), but lack detectable calbindin later in development. To explore the intra-SCN network in which GRP neurons participate, individual GFP+ cells were filled with tracer and their morphological characteristics, processes, and connections, as well as those of their non-GFP containing immediate neighbors, were compared. The results show that GFP+ neurons form a dense network of local circuits within the core, revealed by appositions on other GFP+ cells and by the presence of dye-coupled cells. Dendrites and axons of GFP+ cells make appositions on arginine vasopressin neurons, while non-GFP cells have a less extensive fiber network, largely confined to the region of GFP+ cells. The results point to specialized circuitry within the SCN, presumably supporting synchronization of neural activity and reciprocal communication between core and shell regions. PMID:20151358

  12. Site-specific effects of gastrin-releasing peptide in the suprachiasmatic nucleus

    PubMed Central

    Kallingal, George J.; Mintz, Eric M.

    2013-01-01

    The effects of gastrin-releasing peptide (GRP) on the circadian clock in the suprachiasmatic nucleus (SCN) are dependent on the activation of N-methyl-d-aspartate (NMDA) receptors in the SCN. In this study, the interaction between GRP, glutamate and serotonin in the regulation of circadian phase in Syrian hamsters was evaluated. Microinjection of GRP into the third ventricle induced c-fos and p-ERK expression throughout the SCN. Coadministration of an NMDA antagonist or 8-hydroxy-2-di-n-propylamino-tetralin [a serotonin (5-HT)1A,7 agonist, DPAT] with GRP limited c-fos expression in the SCN to a region dorsal to GRP cell bodies. Similar to the effects of NMDA antagonists, DPAT attenuated GRP-induced phase shifts in the early night, suggesting that the actions of serotonin on the photic phase shifting mechanism occur downstream from retinorecipient cells. c-fos and p-ERK immunoreactivity in the supraoptic (SON) and paraventricular hypothalamic nuclei also increased following ventricular microinjection of GRP. Because of this finding, a second set of experiments was designed to test a potential role for the SON in the regulation of clock function. Syrian hamsters were given microinjections of GRP into the peri-SON during the early night. GRP-induced c-fos activity in the SCN was similar to that following ventricular administration of GRP. GRP or bicuculline (a γ-aminobutyric acidA antagonist) administered near the SON during the early night elicited phase delays of circadian activity rhythms. These data suggest that GRP-induced phase-resetting is dependent on levels of glutamatergic and serotonergic neurotransmission in the SCN and implicate activity in the SON as a potential regulator of photic signaling in the SCN. PMID:24528136

  13. Quantifying tumour heterogeneity with CT

    PubMed Central

    Miles, Kenneth A.

    2013-01-01

    Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171

  14. Leydig cell tumours in childhood.

    PubMed

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  15. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  16. Multicellular Streaming in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Kas, Josef

    As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  17. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  18. Imaging of skull base tumours.

    PubMed

    Thust, Stefanie Catherine; Yousry, Tarek

    2016-01-01

    The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours. PMID:27330416

  19. Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic/associative and sensorimotor cortical areas

    PubMed Central

    Heng, Lijun; Beverley, Joel A.; Steiner, Heinz; Tseng, Kuei Y.

    2010-01-01

    Cannabis use during adolescence is associated with an increased risk for schizophrenia and other disorders. The neuronal basis is unclear, but prefrontal cortical mechanisms have been implicated. Here, we investigated developmental changes in the endocannabinoid system by assessing expression and function of the CB1 cannabinoid receptor in prefrontal and other cortical areas in juvenile (postnatal day 25, P25), adolescent (P40) and adult (P70) rats. Overall, the expression of CB1 receptors in the cortex is highest in juveniles and drops thereafter towards adult levels. However, CB1 receptor expression follows distinct developmental trajectories in different cortical areas. The most pronounced and progressive decrease in CB1 expression was observed in medial prefrontal and other limbic/associative regions. In contrast, major changes in sensorimotor cortices occurred only after P40. We also assessed electrophysiological measures of CB1 receptor function and found that CB1-dependent inhibition of synaptic transmission in the prefrontal cortex follows the same developmental trajectory as observed for receptor expression. Together, these findings indicate that CB1 receptor-mediated signaling decreases during development, but is differentially regulated in limbic/associative vs. sensorimotor systems. Therefore, cannabis use during adolescence likely differentially affects limbic/associative and sensorimotor cortical circuits. PMID:20687106

  20. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  1. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  2. Prenatal stress alters diazepam withdrawal syndrome and 5HT1A receptor expression in the raphe nuclei of adult rats.

    PubMed

    Lakehayli, S; Said, N; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2016-08-25

    Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats. PMID:27235743

  3. Modulation of transmembrane signalling in HL-60 granulocytes by tumour necrosis factor-alpha.

    PubMed Central

    McLeish, K R; Klein, J B; Schepers, T; Sonnenfeld, G

    1991-01-01

    Differentiated HL-60 granulocytes were used to study the mechanism by which tumour necrosis factor-alpha (TNF) enhances responses to N-formyl-methionyl-leucylphenylalanine (FMLP). Cultivation of differentiated HL-60 cells with 100 units of TNF/ml for 24 h resulted in a 3-fold increase in superoxide release and 4-fold increase in prostaglandin E2 production on stimulation with 1 microM-FMLP. On the other hand, cultivation with TNF failed to increase phorbol diester stimulation of superoxide release. Formyl-peptide-receptor expression determined on isolated membranes from cells cultivated with TNF (TNF-M) was increased by 50% compared with membranes from control cells (NM). Similarly, FMLP binding to intact HL-60 cells was increased by cultivation with TNF. Guanine-nucleotide-binding proteins (G-protein) levels were not different between TNF-M and NM, as determined by pertussis-toxin-catalysed ADP-ribosylation and by immunoblotting with antisera recognizing alpha i2 subunit. Binding of guanosine 5'-[gamma-thio]triphosphate and GTP hydrolysis stimulated by FMLP were enhanced by about 50% in TNF-M. The efficiency of G-protein activation by formyl-peptide receptors did not differ between TNF-M and NM. TNF regulates expression of formyl-peptide receptors independently of G-protein levels. The regulation of receptor expression is one mechanism by which TNF enhances cell responses to formylated peptides. Images Fig. 4. PMID:1659380

  4. Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis.

    PubMed

    Ludvigsen, Eva

    2007-01-01

    Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of

  5. Critical evaluation of the expression of gastrin-releasing peptide in dorsal root ganglia and spinal cord

    PubMed Central

    Barry, Devin M; Li, Hui; Liu, Xian-Yu; Shen, Kai-Feng; Liu, Xue-Ting; Wu, Zhen-Yu; Munanairi, Admire; Chen, Xiao-Jun; Yin, Jun; Sun, Yan-Gang; Li, Yun-Qing

    2016-01-01

    There are substantial disagreements about the expression of gastrin-releasing peptide (GRP) in sensory neurons and whether GRP antibody cross-reacts with substance P (SP). These concerns necessitate a critical revaluation of GRP expression using additional approaches. Here, we show that a widely used GRP antibody specifically recognizes GRP but not SP. In the spinal cord of mice lacking SP (Tac1 KO), the expression of not only GRP but also other peptides, notably neuropeptide Y (NPY), is significantly diminished. We detected Grp mRNA in dorsal root ganglias using reverse transcription polymerase chain reaction, in situ hybridization and RNA-seq. We demonstrated that Grp mRNA and protein are upregulated in dorsal root ganglias, but not in the spinal cord, of mice with chronic itch. Few GRP+ immunostaining signals were detected in spinal sections following dorsal rhizotomy and GRP+ cell bodies were not detected in dissociated dorsal horn neurons. Ultrastructural analysis further shows that substantially more GRPergic fibers form synaptic contacts with gastrin releasing peptide receptor-positive (GRPR+) neurons than SPergic fibers. Our comprehensive study demonstrates that a majority of GRPergic fibers are of primary afferent origin. A number of factors such as low copy number of Grp transcripts, small percentage of cells expressing Grp, and the use of an eGFP GENSAT transgenic as a surrogate for GRP protein have contributed to the controversy. Optimization of experimental procedures facilitates the specific detection of GRP expression in dorsal root ganglia neurons. PMID:27068287

  6. Therapy-induced tumour secretomes promote resistance and tumour progression

    PubMed Central

    Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan

    2015-01-01

    Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485

  7. Inhibition by somatostatin (growth-hormone release-inhibiting hormone, GH-RIH) of gastric acid and pepsin and G-cell release of gastrin.

    PubMed Central

    Barros D'sa, A A; Bloom, S R; Baron, J H

    1978-01-01

    Somatostatin (cyclic growth-hormone release-inhibiting hormone--GH-RIH) was infused into dogs with gastric fistulae. Somatostatin inhibited gastric acid response to four gastric stimulants--insulin, food, histamine, and pentagastrin. Histamine- and pentagastrin-stimulated pepsins were inhibited similarly to inhibition of acid. Somatostatin inhibited the gastrin response to insulin and food. PMID:348581

  8. Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk

    PubMed Central

    Pohjanen, Vesa-Matti; Koivurova, Olli-Pekka; Huhta, Heikki; Helminen, Olli; Mäkinen, Johanna M.; Karhukorpi, Jari M.; Joensuu, Tapio; Koistinen, Pentti O.; Valtonen, Jarno M.; Niemelä, Seppo E.; Karttunen, Riitta A.; Karttunen, Tuomo J.

    2015-01-01

    Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion. PMID:26161647

  9. Tumours of the upper alimentary tract.

    PubMed

    Head, K W

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. PMID:1086147

  10. Cyclin D1 amplification and expression in human breast carcinoma: correlation with histological prognostic markers and oestrogen receptor expression

    PubMed Central

    Worsley, S D; Jennings, B A; Khalil, K H; Mole, M; Girling, A C

    1996-01-01

    Aims—To study the amplification of the Cyclin D1 gene (CCND1) in human breast carcinoma; to relate this to Cyclin D1 protein expression; to relate these parameters to recognised pathological prognostic factors, including oestrogen receptor (ER) status. Methods—DNA extracted from frozen sections of breast tumours (n = 36) was used for Southern blotting. Probes for CCND1, c-myc and the immunoglobulin heavy chain locus (IgH) were hybridised to tumour DNA. Immunocytochemical expression of Cyclin D1 protein and ER was studied in paraffin wax sections from the same tumours. Results—Amplification of CCND1 was observed in 11% (four of 36) of tumours studied. Over expression of Cyclin D1 protein was observed in 73% (30/41) of tumours. There was no correlation between recognised histological prognostic markers and either gene amplification or expression. However, a weak association was seen between Cyclin D1 expression and ER status. Conclusions—A disparity exists between locus amplification and over expression of Cyclin D1, suggesting the existence of another mechanism for raised protein expression. No significant correlation was detected between either Cyclin D1 amplification or over expression and established prognostic markers. Images PMID:16696045

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

    PubMed Central

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

    2015-01-01

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

  12. Axospinous synaptic subtype-specific differences in structure, size, ionotropic receptor expression, and connectivity in apical dendritic regions of rat hippocampal CA1 pyramidal neurons

    PubMed Central

    Nicholson, Daniel A.; Geinisman, Yuri

    2008-01-01

    The morphology of axospinous synapses and their parent spines varies widely. Additionally, many of these synapses are contacted by multiple synapse boutons (MSBs) and show substantial variability in receptor expression. The two major axospinous synaptic subtypes are perforated and nonperforated, but there are several subcategories within these two classes. The present study used serial section electron microscopy to determine whether perforated and nonperforated synaptic subtypes differed with regard to their distribution, size, receptor expression, and connectivity to MSBs in three apical dendritic regions of rat hippocampal area CA1: the proximal and distal thirds of stratum radiatum, and stratum lacunosum-moleculare. All synaptic subtypes were present throughout the apical dendritic regions, but there were several subclass-specific differences. First, segmented, completely partitioned synapses changed in number, proportion, and AMPA receptor expression with distance from the soma beyond that found within other perforated synaptic subtypes. Second, atypically large nonperforated synapses showed NMDA receptor immunoreactivity identical to perforated synapses, levels of AMPA receptor expression intermediate to nonperforated and perforated synapses, and perforated synapse-like changes in structure with distance from the soma. Finally, MSB connectivity was highest in proximal stratum radiatum, but only for those MSBs comprised of nonperforated synapses. The immunogold data suggest that most MSBs would not generate simultaneous depolarizations in multiple neurons or spines, however, because the vast majority of MSBs are comprised of two synapses with abnormally low levels of receptor expression, or involve one synapse with a high level of receptor expression and another with only a low level. PMID:19006199

  13. Oncoprotein stability after tumour resection.

    PubMed Central

    Ong, G.; Gullick, W.; Sikora, K.

    1990-01-01

    The means by which oncogenes and their products activate malignant transformation are currently under intense investigation. However, published papers on experiments using human tumour material do not always report in detail their methods of collection or storage of the specimens. In order to assess the stability of oncogene encoded proteins following collection or storage of human tumour biopsies, we have examined the rate of decay of the c-myc, neu and EGF-receptor proteins. Solid tumours, containing amplified copies of each oncogene, were established in nude mice and the stability of the oncogene protein in portions of each tumour, left in phosphate buffered saline at room temperature for varying time intervals, was examined by immunoblotting. Intact EGF-receptor and neu oncoproteins were present even after 24 h under these conditions while the c-myc protein was apparently rapidly degraded after 20 min. These data demonstrate that oncogene products decay at different rates after tumour resection and that collection of human biopsies should take this into account in order to provide the basis for consistent measurements of protein expression. Images Figure 1 Figure 2 Figure 3 PMID:2139576

  14. Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin

    PubMed Central

    Song, Imane; Patel, Oelfah; Himpe, Eddy; Muller, Christo J. F.; Bouwens, Luc

    2015-01-01

    One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The

  15. Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin.

    PubMed

    Song, Imane; Patel, Oelfah; Himpe, Eddy; Muller, Christo J F; Bouwens, Luc

    2015-01-01

    One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The

  16. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  17. Tumour-associated eosinophilia: a review.

    PubMed Central

    Lowe, D; Jorizzo, J; Hutt, M S

    1981-01-01

    In a recent study of cervical carcinoma, 13 cases with a marked eosinophil infiltrate around the tumour were found. The histological appearance of the tumours was distinctive and suggested a specific response, similar to the lymphocyte infiltration in medullary carcinoma of the breast and seminoma. A review of published reports shows that tumour-associated tissue eosinophilia (TATE) and tumour-associated blood eosinophilia (TABE) may be seen in tumours of different histological types from different anatomical sites, and may occur together or separately. Tumours with TATE alone appear to have a better prognosis that those without, while TABE is associated with tumor spread and a poor prognosis. Images PMID:7035499

  18. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  19. Prenatal stress induces vulnerability to nicotine addiction and alters D2 receptors' expression in the nucleus accumbens in adult rats.

    PubMed

    Said, N; Lakehayli, S; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2015-09-24

    Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC). These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression. PMID:26192093

  20. Natural killer cell receptor expression in patients with severe and recurrent Herpes simplex virus-1 (HSV-1) infections.

    PubMed

    Carter, C; Savic, S; Cole, J; Wood, P

    2007-04-01

    Herpes simplex virus-1 (HSV-1) is an important human pathogen which in a minority of people causes severe infections. In immunocompetent hosts the infection is self limiting. However, a small minority of people have frequent attacks. As NK cells have been implicated in host protection against HSV-1, the aim of this study was to compare NK cell receptor expression in healthy controls and in patients suffering from recurrent HSV-1 reactivations using monoclonal antibodies against NK cell receptors and 3 colour flow cytometry. Eighteen patients were recruited into the study and the results were compared to a control group. The results obtained showed that overall there was no statistical difference between patient and control groups in the expression of the NK cell receptors. There were however, individuals in the patient group (in particular, two members of one family) with significantly reduced level of activating receptors compared to the control group. PMID:17706187

  1. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    PubMed Central

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  2. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.

    PubMed

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-Ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  3. Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep.

    PubMed

    Marshall, Allyson C; Shaltout, Hossam A; Nautiyal, Manisha; Rose, James C; Chappell, Mark C; Diz, Debra I

    2013-06-01

    Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30±0.36 versus 0.99±0.28; p<0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78±0.06 vs. 1.94±0.41; p<0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model. PMID:23538211

  4. Glucocorticoids down-regulate beta 1-adrenergic-receptor expression by suppressing transcription of the receptor gene.

    PubMed Central

    Kiely, J; Hadcock, J R; Bahouth, S W; Malbon, C C

    1994-01-01

    The expression of beta 2-adrenergic receptors is up-regulated by glucocorticoids. In contrast, beta 1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-adrenergic receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-adrenergic receptors. Images Figure 1 Figure 2 Figure 6 PMID:8092990

  5. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    PubMed

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  6. Tailored nanoparticles for tumour therapy.

    PubMed

    Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju; Kao, Chao-Hung; Lee, Kun-Feng; Kuo, Chien-Hung; Lin, Xi-Zhang; Lin, Yuh-Jiuan

    2012-06-01

    Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment. PMID:22905580

  7. Brown tumour of the jaw

    PubMed Central

    Nair, Preeti P; Gharote, Harshkant P; Thomas, Shaji; R, Guruprasad; Singh, Neha

    2011-01-01

    Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented. PMID:22669885

  8. A rare urinary bladder tumour

    PubMed Central

    Haddad-Lacle, Judella Edwina Maria; Haddad, Charles Joseph; Villas, Bruce

    2014-01-01

    This case report describes a 54-year-old man who presented to his primary care physician with low back pain. During his workup, an incidental finding of a bladder mass was diagnosed. He underwent transurethral resection of the bladder tumour and the resulting pathology was consistent with extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Presentation of MALT lymphoma in the urinary bladder is rare. This malignancy is more commonly found in the stomach. The prognosis for this rare tumour is excellent. Our patient showed no sign of recurrence with transurethral excision and radiation alone. PMID:24835803

  9. Tumours of the soft (mesenchymal) tissues.

    PubMed

    Weiss, E

    1974-01-01

    This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs. PMID:4371740

  10. Brain tumour mortality in immigrants.

    PubMed

    Neutel, C I; Quinn, A; Brancker, A

    1989-03-01

    All Canadian deaths due to malignant brain tumour for the years 1970-73 were identified and analysed for country of birth. The years 1970-73 were chosen since in later years country of birth was no longer available for each death. The brain tumour population consisted of 1551 male and 1058 female deaths and matched controls were chosen from deaths due to other causes. Americans who died of brain tumour in Canada had a standardized mortality ratio (SMR) of 1.0 compared to their fellow Americans in the USA. Italian, German, Dutch and British immigrants had SMR between 1.5 and 2.6 compared to rates in their home countries and between 1.24 and 2.09 when compared to Canadian rates. A series of graphs shows the increased risk for male immigrants quite dramatically, and indicates that for females the increases were less pronounced. Further analysis showed that the excess risk is confined to those who were born in Western Europe while their Canadian-born children experienced the same rates as all Canadians. Based on the limited information available, occupation could not be shown to play a role in establishing risk. An attempt was made to pinpoint the years of immigration which showed the greatest risk. It is concluded that the determination of risk of brain tumour has a strong environmental component. The possibilities for identification of this component are discussed. PMID:2722385

  11. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  12. Nucleus Accumbens Dopamine D2-Receptor Expressing Neurons Control Behavioral Flexibility in a Place Discrimination Task in the IntelliCage

    ERIC Educational Resources Information Center

    Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

    2016-01-01

    Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated…

  13. Characterization of antisecretory and antiulcer activity of CR 2945, a new potent and selective gastrin/CCK(B) receptor antagonist.

    PubMed

    Makovec, F; Revel, L; Letari, O; Mennuni, L; Impicciatore, M

    1999-03-12

    The antigastrinic, antisecretory and antiulcer activities of CR 2945, (R)-1-naphthalenepropanoic acid,beta-[2-[[2-(8-azaspiro[4.5]dec-8-yl-carbonyl)-4,6-dimethylph enyl] amino]-2-oxoethyl], were investigated in vitro and in vivo in rats and cats. Its activities were compared with those of two gastrin/CCK(B) receptor antagonists, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)-N'-(3-methylphenyl)urea and CAM-1028 (4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[1,7,7-trimethylbicyclo [2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino -4-oxo-[1S-1alpha,2beta[S'(S')4alpha

  14. Tumour vasculature--a potential therapeutic target.

    PubMed Central

    Baillie, C. T.; Winslet, M. C.; Bradley, N. J.

    1995-01-01

    The tumour vasculature is vital for the establishment, growth and metastasis of solid tumours. Its physiological properties limit the effectiveness of conventional anti-cancer strategies. Therapeutic approaches directed at the tumour vasculature are reviewed, suggesting the potential of anti-angiogenesis and the targeting of vascular proliferation antigens as cancer treatments. PMID:7543770

  15. Chondrocyte IGF-1 receptor expression and responsiveness to IGF-1 stimulation in mouse articular cartilage during various phases of experimentally induced arthritis.

    PubMed Central

    Verschure, P J; van Marle, J; Joosten, L A; van den Berg, W B

    1995-01-01

    OBJECTIVE--To examine the distribution of insulin like growth factor-1 (IGF-1) receptors and the biological response to IGF-1 stimulation in articular cartilage of normal mouse knee joints and arthritic joints taken at various stages of experimentally induced arthritis. METHODS--In situ IGF-1 receptor expression and responsiveness to IGF-1 stimulation were examined in murine articular cartilage at different phases in two models of experimentally induced arthritis. IGF-1 receptor expression was visualised in joint sections with the use of anti-IGF-1 receptor antibodies and quantified by confocal laser scanning microscopy. Chondrocyte proteoglycan (PG) synthesis was measured by incorporation of 35S-sulphate. RESULTS--In control cartilage, the majority of IGF-1 receptors were found on chondrocytes localised in the middle and deeper zones of the cartilage, whereas receptor expression in surface zone chondrocytes was very low. During culture of normal articular cartilage, IGF-1 was able to maintain chondrocyte PG synthesis at the in vivo level. Concurrently with the development of arthritis, cartilage lost its capacity to react to IGF-1, but IGF-1 stimulation recovered when the inflammatory response waned. Shortly after induction of arthritis, IGF-1 receptor expression initially declined, but it had returned to normal levels by day 1 and remained increased thereafter. CONCLUSION--The distribution of IGF-1 receptor expression in the different zones of normal articular cartilage reflects IGF-1 stimulation and metabolic activity of chondrocytes in these layers. This correlation is disturbed in arthritic cartilage, suggesting inadequate or overruled signalling. Images PMID:7677441

  16. Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

    PubMed Central

    Fischer, C P; Bode, B P; Takahashi, K; Tanabe, K K; Souba, W W

    1996-01-01

    OBJECTIVE: The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. SUMMARY BACKGROUND DATA: Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. METHODS: Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. RESULTS: Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. CONCLUSIONS: Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL

  17. Animal models of tumour-associated epilepsy.

    PubMed

    Kirschstein, Timo; Köhling, Rüdiger

    2016-02-15

    Brain tumours cause a sizeable proportion of epilepsies in adulthood, and actually can be etiologically responsible also for childhood epilepsies. Conversely, seizures are often first clinical signs of a brain tumour. Nevertheless, several issues of brain-tumour associated seizures and epilepsies are far from understood, or clarified regarding clinical consensus. These include both the specific mechanisms of epileptogenesis related to different tumour types, the possible relationship between malignancy and seizure emergence, the interaction between tumour mass and surrounding neuronal networks, and - not least - the best treatment options depending on different tumour types. To investigate these issues, experimental models of tumour-induced epilepsies are necessary. This review concentrates on the description of currently used models, focusing on methodological aspects. It highlights advantages and shortcomings of these models, and identifies future experimental challenges. PMID:26092434

  18. Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine.

    PubMed

    Barlos, K; Gatos, D; Kapolos, S; Poulos, C; Schäfer, W; Yao, W Q

    1991-12-01

    The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH2, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu15)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloromethane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide. PMID:1819590

  19. Expression of the pNR-2/pS2 protein in diverse human epithelial tumours.

    PubMed Central

    Henry, J. A.; Bennett, M. K.; Piggott, N. H.; Levett, D. L.; May, F. E.; Westley, B. R.

    1991-01-01

    The pNR-2/pS2 protein is regulated by oestrogens in breast cancer cell lines. This report describes a systematic survey of pNR-2/pS2 expression in a number of common epithelial tumours. Expression was evaluated immunohistochemically in an archival series using antisera raised against the C-terminus of the pNR-2/pS2 protein. Expression of pNR-2/pS2 by malignant epithelial tumours was widespread. Intense immunohistochemical staining was found in tumour cells in a proportion of pancreatic (6/8), large intestinal (7/12), gastric (9/16) and endometrial (4/12) carcinomas. Positive staining for the pNR-2/pS2 protein was also found in both benign and malignant ovarian epithelial tumours and was very significantly associated with mucinous differentiation (P less than 0.00001). Small numbers of carcinomas of bladder (2/10) and prostate (2/7) showed less intense staining and single examples of cervical carcinoma (1/7) and lung carcinoma (1/19) stained positively. None of the renal carcinomas (0/16) examined stained positively. Positive staining showed no correlation with gender. Although there are reports of oestrogen receptor expression in most of the tumour types considered, the possibility of other regulatory influences must also be considered. The pNR-2/pS2 protein may well have a more general role in human epithelial neoplasia than hitherto realised. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1911216

  20. Haemangioleiomyomatous tumour of the lung.

    PubMed Central

    Soorae, A S; Bharucha, H

    1980-01-01

    A case of haemangioleiomyomatous tumour of the lung, occurring as a peripheral, solitary nodule in an asymptomatic 54-year-old man is presented. The tumour was well-demarcated and microscopically it was characterised by the presence of vascular spaces with endothelial, pericytic, and, predominantly, smooth muscle proliferation. Islands of cartilage and slit-like spaces lined by bronchial epithelium make this a hamartomatous lesion of a quite distinctive and unusual variety, which does not fit any of the well-recognised patterns of hamartomas previously described. The long-term prognosis after limited excision is considered to be favourable. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7358861

  1. Evidence for estrogen receptor expression in germ cell and somatic cell subpopulations in the ovary of the newly hatched chicken.

    PubMed

    Méndez, M C; Chávez, B; Echeverría, O; Vilchis, F; Vázquez Nin, G H; Pedernera, E

    1999-10-01

    Estrogens are involved in the gonadal morphogenesis of vertebrates, and almost all hormonal effects of 17beta-estradiol are mediated through specific receptors. At the time of sexual differentiation in the chicken, or even before, there is evidence of the presence of estrogen receptors and the secretion of 17beta-estradiol. However, no information is available regarding the cellular types that express the estrogen receptor in the immature chick ovary. The present study analyzes estrogen receptor expression in germ and somatic cells of the ovary in the newly hatched chicken. Highly purified cell subpopulations of germ and somatic cells were evaluated for specific 17beta-estradiol nuclear binding. In addition, the estrogen receptor was localized at the ultrastructural level by the immunogold technique. Finally, reverse transcription and polymerase chain reaction procedures detected a steady-state level of mRNA for the estrogen receptor. Somatic cells including typical steroidogenic cells showed specific 17beta-estradiol nuclear binding, displayed the estrogen receptor, and possessed estrogen receptor transcripts. The same result was observed in primary oocytes, together with the ultrastructural localization of estrogen receptor in extended chromatin filaments. Our experimental data support the hypothesis that estrogens are involved in the function of somatic and germ cells subpopulations in the immature chicken ovary. PMID:10555548

  2. Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression.

    PubMed

    Korhonen, Katariina; Salminen, Tiina; Raitanen, Jani; Auvinen, Anssi; Isola, Jorma; Haapasalo, Hannu

    2006-10-01

    The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression. PMID:16703453

  3. Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF-β therapy.

    PubMed

    Karam, Rehab A; Rezk, Noha A; Amer, Mona M; Fathy, Hala A

    2016-09-01

    Interferon (IFN)-β is one of the disease modifying drugs used in the treatment of multiple sclerosis. A predictive marker that indicates good or poor response to the treatment is highly desirable. We aimed to investigate the relation between the immune response genes receptors (IFNAR1, IFNAR2, and CCR5) expression and their polymorhic variants and multiple sclerosis (MS) susceptibility as well as the response to IFN-β therapy. The immune response genes receptors expression and genotyping were analyzed in 80 patients with MS, treated with IFN-β and in 110 healthy controls. There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group. Also, the level of IFNAR1, IFNAR2, and CCR5 mRNA expression was found to be significantly lower in the responders than nonresponders. Carriers of IFNAR1 18417 C/C genotype and C allele had an increased risk of developing MS. There was a significant relation between CCR5 Δ32 allele and IFN-β treatment response in MS patients. Our results highlighted the significance of IFNAR and CCR5 genes in multiple sclerosis risk and the response to IFN-β therapy. © 2016 IUBMB Life, 68(9):727-734, 2016. PMID:27346865

  4. Clinical verification of sensitivity to preoperative chemotherapy in cases of androgen receptor-expressing positive breast cancer

    PubMed Central

    Asano, Yuka; Kashiwagi, Shinichiro; Onoda, Naoyoshi; Kurata, Kento; Morisaki, Tamami; Noda, Satoru; Takashima, Tsutomu; Ohsawa, Masahiko; Kitagawa, Seiichi; Hirakawa, Kosei

    2016-01-01

    Background: Triple-negative breast cancer (TNBC) patients testing positive for androgen receptor (AR) expression are thought to be chemotherapy resistant, similar to other hormone receptor-positive breast cancers; however, this has not been substantially validated in the clinic. In this study, we investigated the association between chemotherapy sensitivity and AR expression in patients treated with neoadjuvant chemotherapy (NAC) using standardised chemotherapy criteria and regimens. Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Oestrogen receptor, progesterone receptor, HER2, Ki67 and AR status were assessed immunohistochemically. Results: Sixty-one patients were diagnosed with TNBC; AR expression was identified in 23 (37.7%), which was significantly less common than that found in non-TNBC patients (103 of 116; 88.8% P<0.001). The rate of pathological complete response after NAC was significantly lower (P=0.001), and disease recurrence was more common (P=0.008) in patients with AR-positive compared with those with AR-negative TNBC. In TNBC cases, as expected, the non-recurrence period in cases that were negative for AR expression was significantly extended (P=0.006, log-rank). Conclusions: Androgen receptor expressions may be useful as biomarkers to predict treatment responses to NAC in TNBC. Moreover, induction of a change in subtype to the AR-negative phenotype was observed after NAC. PMID:26757422

  5. Genomic structure, promoter identification, and chromosomal mapping of a mouse nuclear orphan receptor expressed in embryos and adult testes

    SciTech Connect

    Lee, C.H.; Wei, Li-Na; Copeland, N.G.; Gilbert, D.J.; Jenkins, N.A.

    1995-11-01

    We have isolated and characterized overlapping genomic clones containing the complete transcribed region of a newly isolated mouse cDNA encoding an orphan receptor expressed specifically in midgestation embryos and adult testis. This gene spans a distance of more than 50 kb and is organized into 13 exons. The transcription initiation site is located at the 158th nucleotide upstream from the translation initiation codon. All the exon/intron junction sequences follow the GT/AG rule. Based upon Northern blot analysis and the size of the transcribed region of the gene, its transcript was determined to be approximately 2.5 kb. Within approximately 500 hp upstream from the transcription initiation site, several immune response regulatory elements were identified but no TATA box was located. This gene was mapped to the distal region of mouse chromosome 10 and its locus has been designated Tr2-11. Immunohistochemical studies show that the Tr2-11 protein is present mainly in advanced germ cell populations of mature testes and that Tr2-11 gene expression is dramatically decreased in vitamin A-depleted animals. 23 refs., 7 figs.

  6. Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain.

    PubMed

    Yanai, Toshihiro; Kurosawa, Aya; Nikaido, Yoshiaki; Nakajima, Nozomi; Saito, Tamio; Osada, Hiroyuki; Konno, Ayumu; Hirai, Hirokazu; Takeda, Shigeki

    2016-07-01

    The identification of novel synthetic ligands for G protein-coupled receptors (GPCRs) is important not only for understanding human physiology, but also for the development of novel drugs, especially for orphan GPCRs for which endogenous ligands are unknown. One of the orphan GPCR subfamilies, Super conserved Receptor Expressed in Brain (SREB), consists of GPR27, GPR85 and GPR173 and is expressed in the central nervous system. We report herein the identification of inverse agonists for the SREB family without their agonists. We carried out an in vitro screening of 5472 chemical compounds from the RIKEN NPDepo chemical library. The binding of [(35) S]GTPγS to the GPR173-Gsα fusion protein expressed in Sf9 cells was measured and resulted in the identification of 8 novel GPR173 inverse agonists. The most potent compound showed an IC50 of approximately 8 μm. The identified compounds were also antagonists for other SREB members, GPR27 and GPR85. These results indicated that the SREB family could couple Gs-type G proteins, and SREB-Gsα fusion proteins showed significant constitutive activities. Moreover, a molecular model of GPR173 was constructed using the screening results. The combination of computational and biological methods will provide a unique approach to ligand identification for orphan GPCRs and brain research. PMID:27184081

  7. Soluble Triggering Receptor Expressed on Myeloid Cells 1 Is Released in Patients with Stable Chronic Obstructive Pulmonary Disease

    PubMed Central

    Radsak, Markus P.; Taube, Christian; Haselmayer, Philipp; Tenzer, Stefan; Salih, Helmut R.; Wiewrodt, Rainer; Buhl, Roland; Schild, Hansjörg

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disease that is associated with increased serum levels of markers of systemic inflammation. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently identified activating receptor on neutrophils, monocytes, and macrophage subsets. TREM-1 expression is upregulated by microbial products such as the toll-like receptor ligand lipoteichoic acid of Gram-positive or lipopolysaccharides of Gram-negative bacteria. In the present study, sera from 12 COPD patients (GOLD stages I–IV, FEV1 51 ± 6%) and 10 healthy individuals were retrospectively analyzed for soluble TREM-1 (sTREM-1) using a newly developed ELISA. In healthy subjects, sTREM-1 levels were low (median 0.25 ng/mL, range 0–5.9 ng/mL). In contrast, levels of sTREM-1 in sera of COPD patients were significantly increased (median 11.68 ng/mL, range 6.2–41.9 ng/mL, P<.05). Furthermore, serum levels of sTREM-1 showed a significant negative correlation with lung function impairment. In summary, serum concentrations of sTREM-1 are increased in patients with COPD. Prospective studies are warranted to evaluate the relevance of sTREM-1 as a potential marker of the disease in patients with COPD. PMID:18317529

  8. Triggering receptor expressed on myeloid cells-2 fine-tunes inflammatory responses in murine Gram-negative sepsis.

    PubMed

    Gawish, Riem; Martins, Rui; Böhm, Benedikta; Wimberger, Terje; Sharif, Omar; Lakovits, Karin; Schmidt, Mariane; Knapp, Sylvia

    2015-04-01

    During infections, TLR-mediated responses require tight regulation to allow for pathogen removal, while preventing overwhelming inflammation and immunopathology. The triggering receptor expressed on myeloid cells (TREM)-2 negatively regulates inflammation by macrophages and impacts on phagocytosis, but the function of endogenous TREM-2 during infections is poorly understood. We investigated TREM-2's role in regulating TLR4-mediated inflammation by studying wild-type and TREM-2(-/-) mice challenged with LPS and found TREM-2 to dampen early inflammation. Augmented early inflammation in TREM-2(-/-) animals was followed by an accelerated resolution and ultimately improved survival, associated with the induction of the negative regulator A20. Upon infection with Escherichia coli, the otherwise beneficial effect of an exaggerated early immune response in TREM-2(-/-) animals was counteracted by a 50% reduction in bacterial phagocytosis. In line with this, TREM-2(-/-) peritoneal macrophages (PMs) exhibited augmented inflammation following TLR4 stimulation, demonstrating the presence and negative regulatory functionality of TREM-2 on primary PMs. Significantly, we identified a high turnover rate because TREM-2 RNA is 25-fold down-regulated and the protein proteasomally degraded upon LPS encounter, thus ensuring a tightly regulated and versatile system that modulates inflammation. Our results illustrate TREM-2's effects on infection-triggered inflammation and identify TREM-2 as a potential target to prevent overwhelming inflammation while preserving antibacterial-effector functions. PMID:25477281

  9. Hypoxia-mediated tumour targeting.

    PubMed

    Binley, K; Askham, Z; Martin, L; Spearman, H; Day, D; Kingsman, S; Naylor, S

    2003-04-01

    Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy. PMID:12646859

  10. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.

    PubMed

    Pierre, Joseph F; Neuman, Joshua C; Brill, Allison L; Brar, Harpreet K; Thompson, Mary F; Cadena, Mark T; Connors, Kelsey M; Busch, Rebecca A; Heneghan, Aaron F; Cham, Candace M; Jones, Elaina K; Kibbe, Carly R; Davis, Dawn B; Groblewski, Guy E; Kudsk, Kenneth A; Kimple, Michelle E

    2015-09-15

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  11. A New Triggering Receptor Expressed on Myeloid Cells (TREM) Family Member, TLT-6, is Involved in Activation and Proliferation of Macrophages

    PubMed Central

    Won, Kyung-Jong; Park, Sung-Won; Lee, Seunghoon; Kong, Il-Keun; Chae, Jung-Il; Kim, Bokyung; Lee, Eun-Jong

    2015-01-01

    The triggering receptor expressed on myeloid cells (TREM) family, which is abundantly expressed in myeloid lineage cells, plays a pivotal role in innate and adaptive immune response. In this study, we aimed to identify a novel receptor expressed on hematopoietic stem cells (HSCs) by using in silico bioinformatics and to characterize the identified receptor. We thus found the TREM-like transcript (TLT)-6, a new member of TREM family. TLT-6 has a single immunoglobulin domain in the extracellular region and a long cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motif-like domains. TLT-6 transcript was expressed in HSCs, monocytes and macrophages. TLT-6 protein was up-regulated on the surface of bone marrow-derived and peritoneal macrophages by lipopolysaccharide stimulation. TLT-6 exerted anti-proliferative effects in macrophages. Our results demonstrate that TLT-6 may regulate the activation and proliferation of macrophages. PMID:26557807

  12. Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy.

    PubMed

    Konturek, Peter C; Rembiasz, Kazimierz; Konturek, Stanislaw J; Stachura, Jerzy; Bielanski, Wladyslaw; Galuschka, K; Karcz, Danuta; Hahn, Eckhart G

    2003-01-01

    H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 x 20 mg), amoxycillin (2 x 1 g) and clarithromycin (2 x 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic

  13. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  14. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  15. Malignant Leydig cell tumour of the testis.

    PubMed

    Powari, Manish; Kakkar, Nandita; Singh, S K; Rai, R S; Jogai, Sanjay

    2002-01-01

    A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed. PMID:11803271

  16. Tumours of the liver and biliary system

    PubMed Central

    Ponomarkov, V.; Mackey, L. J.

    1976-01-01

    In this histological classification of liver and gall bladder tumours the tumour types largely correspond to those found in man. The most common tumours in this group are liver cell adenoma, hepatocellular carcinoma, and cholangiocarcinoma. ImagesFig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086149

  17. Acetylcholine induces GABA release onto rod bipolar cells through heteromeric nicotinic receptors expressed in A17 amacrine cells

    PubMed Central

    Elgueta, Claudio; Vielma, Alex H.; Palacios, Adrian G.; Schmachtenberg, Oliver

    2015-01-01

    Acetylcholine (ACh) is a major retinal neurotransmitter that modulates visual processing through a large repertoire of cholinergic receptors expressed on different retinal cell types. ACh is released from starburst amacrine cells (SACs) under scotopic conditions, but its effects on cells of the rod pathway have not been investigated. Using whole-cell patch clamp recordings in slices of rat retina, we found that ACh application triggers GABA release onto rod bipolar (RB) cells. GABA was released from A17 amacrine cells and activated postsynaptic GABAA and GABAC receptors in RB cells. The sensitivity of ACh-induced currents to nicotinic ACh receptor (nAChR) antagonists (TMPH ~ mecamylamine > erysodine > DhβE > MLA) together with the differential potency of specific agonists to mimic ACh responses (cytisine >> RJR2403 ~ choline), suggest that A17 cells express heteromeric nAChRs containing the β4 subunit. Activation of nAChRs induced GABA release after Ca2+ accumulation in A17 cell dendrites and varicosities mediated by L-type voltage-gated calcium channels (VGCCs) and intracellular Ca2+ stores. Inhibition of acetylcholinesterase depolarized A17 cells and increased spontaneous inhibitory postsynaptic currents in RB cells, indicating that endogenous ACh enhances GABAergic inhibition of RB cells. Moreover, injection of neostigmine or cytisine reduced the b-wave of the scotopic flash electroretinogram (ERG), suggesting that cholinergic modulation of GABA release controls RB cell activity in vivo. These results describe a novel regulatory mechanism of RB cell inhibition and complement our understanding of the neuromodulatory control of retinal signal processing. PMID:25709566

  18. Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling

    PubMed Central

    Nadjar, Agnes; Layé, Sophie; Leyrolle, Quentin; Gómez-Nicola, Diego; Domercq, María; Pérez-Samartín, Alberto; Sánchez-Zafra, Víctor; Savage, Julie C.; Hui, Chin-Wai; Deudero, Juan J. P.; Brewster, Amy L.; Anderson, Anne E.; Zaldumbide, Laura; Galbarriatu, Lara; Marinas, Ainhoa; Vivanco, Maria dM.; Matute, Carlos; Maletic-Savatic, Mirjana

    2016-01-01

    Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance

  19. High fat diet and body weight have different effects on cannabinoid CB1 receptor expression in rat nodose ganglia

    PubMed Central

    Cluny, N.L.; Baraboi, E.D.; Mackie, K; Burdyga, G.; Richard, D.; Dockray, G.J.; Sharkey, K.A.

    2013-01-01

    Energy balance is regulated, in part, by orexigenic signaling pathways of the vagus nerve. Fasting-induced modifications in the expression of orexigenic signaling systems have been observed in vagal afferents of lean animals. Altered basal cannabinoid (CB)1 receptor expression in the nodose ganglia in obesity has been reported. Whether altered body weight or a high fat diet modifies independent or additive changes in CB1 expression is unknown. We investigated the expression of CB1 and orexin 1 receptor (OX-1R) in nodose ganglia of rats fed ad libitum or food deprived (24h), maintained on low or high fat diets (HFD), with differing body weights. Male Wistar rats were fed chow or HFD (diet-induced obese: DIO or diet-resistant: DR) or were body weight matched to the DR group but fed chow (wmDR). CB1 and OX-1R immunoreactivity were investigated and CB1 mRNA density was determined using in situ hybridization. CB1 immunoreactivity was measured in fasted rats after sulfated cholecystokinin octapeptide (CCK8s) administration. In chow rats, fasting did not modify the level of CB1 mRNA. More CB1 immunoreactive cells were measured in fed DIO, DR and wmDR rats than chow rats; levels increased after fasting in chow and wmDR rats but not in DIO or DR rats. In HFD fasted rats CCK8s did not reduce CB1 immunoreactivity. OX-1R immunoreactivity was modified by fasting only in DR rats. These data suggest that body weight contributes to the proportion of neurons expressing CB1 immunoreactivity in the nodose ganglion, while HFD blunts fasting-induced increases, and CCK-induced suppression of, CB1-immunoreactivity. PMID:24145047

  20. Anabolic steroid- and exercise-induced cardio-depressant cytokines and myocardial β1 receptor expression in CD1 mice.

    PubMed

    Fineschi, Vittorio; Di Paolo, Marco; Neri, Margherita; Bello, Stefania; D'Errico, Stefano; Dinucci, Dinuccio; Parente, Ruggero; Pomara, Cristoforo; Rabozzi, Roberto; Riezzo, Irene; Turillazzi, Emanuela

    2011-02-01

    Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The AAS mice received intramuscular Nandrolone Decanoate (DECA-DURABOLIN), vehicled in arachidis oil, for 42 days, twice per week, with different dosages, studying plasma lipid analysis, cardiac histopathological features, cardiac β (1) adrenergic receptor expression, and the effects of the myocardial expression of inflammatory mediators (IL-1β, TNF-α) on the induction of cardiomyocytes apoptosis (HSP 70, TUNEL), using proteomic and immunohistochemical analysis. The mice had free movements in their animal rooms (two groups) or exercised by running on a motor-driven treadmill the others three groups. Recurring high dose AAS administration and physical training in mice produce significant increase in body weight and for total cholesterol. A moderate increase of the heart weight, cardiac hypertrophy and wide colliquative myocytolysis, were observed in high dose AAS administration and physical training group. The expression of HSP70 and inflammatory cytokine IL-1β, increased in the three AAS-treated groups. TNF- α showed a more extensive expression in the AAS-high dose group. A significant apoptotic process randomly sparse in the myocardium was described. Our data support the hypothesis that the combined effects of vigorous training, anabolic steroid abuse and stimulation of the sympathetic nervous system, may predispose to myocardial injury. PMID:21050164

  1. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy

    PubMed Central

    Lapa, Constantin; Hänscheid, Heribert; Wild, Vanessa; Pelzer, Theo; Schirbel, Andreas; Werner, Rudolf A.; Droll, Sabine; Herrmann, Ken; Buck, Andreas K.; Lückerath, Katharina

    2016-01-01

    Despite initial responsiveness to both chemotherapy and radiotherapy, small cell lung cancer (SCLC) commonly relapses within months. Although neuroendocrine characteristics may be difficult to demonstrate in individual cases, a relevant expression of somatostatin receptors (SSTR) on the cell surface has been described. We aimed to evaluate the prognostic value of SSTR-expression in advanced SCLC. We further examined pre-requisites for successful peptide receptor radionuclide therapy (PRRT). 21 patients with extensive stage SCLC were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTATATE to select patients for SSTR-directed therapy. PET scans were visually and semi-quantitatively assessed and compared to SSTR2a and SSTR5 expression in biopsy samples. Peak standardized uptake values (SUVpeak) of tumors as well as tumor-to-liver ratios were correlated to progression-free (PFS) and overall survival (OS). In 4/21 patients all SCLC lesions were PET-positive. 6/21 subjects were rated “intermediate” with the majority of lesions positive, the remaining 11/21 patients were PET-negative. PET-positivity correlated well with histologic SSTR2a, but not with SSTR5 expression. Neither PET-positivity nor SUVpeak were predictors of PFS or OS. In 4 patients with intensive SSTR2a-receptor expression, PRRT was performed with one partial response and one stable disease, respectively. SSTR-expression as detected by 68Ga-DOTATATE-PET and/or histology is not predictive of PFS or OS in patients with advanced SCLC. However, in patients exhibiting sufficient tracer uptake, PRRT might be a treatment option given its low toxicity and the absence of effective alternatives. PMID:26936994

  2. Estrogen and androgen receptor expression in surface epithelium and inclusion cyst in the ovary of premenopausal and postmenopausal women

    PubMed Central

    2013-01-01

    Background The importance of surface epithelium and epithelial inclusion cysts in the ovary arises from studies demonstrating that these structures are susceptible to epithelial ovarian cancer development. The expression of estrogen receptor alpha (ER alpha), androgen receptor (AR), in epithelial cells of the ovary from premenopausal and postmenopausal women is interesting because sexual steroid hormones are involved in cell growth and differentiation. Methods The presence of ER alpha, AR, and the orphan G protein-coupled receptor 30 (GPR30) was demonstrated by immunofluorescence in ovaries obtained from 79 pre and postmenopausal patients, undergoing histero-salpingo-oophorectomy for proliferative gynecological diseases. The proportion of patients that displayed positive reaction for estrogen and androgen receptors in epithelial cells of the ovary was evaluated according to menopausal status and associated pathology. Results The proportion of patients that displayed a positive receptor expression in the epithelial cells of the ovarian surface and cortical inclusion cysts shows that ER alpha is present in 20 of 79 patients (0.25), AR in 33 of 79 (0.42) and GPR30 in 38 of 55 (0.69). There are no differences in ER alpha, AR, and GPR30 expression between pre and postmenopausal patients and considering the associated pathology, proportions for ER alpha and GPR30 are similar. The patients with cervical cancer show a higher proportion of AR expression in epithelial cells of the ovary, which is statistically significant (P < 0.01) compared with patients with other proliferative diseases. Conclusions The presence of ER alpha, AR, and GPR30 in the surface epithelial ovarian cells and its derivatives are observed with a proportion that is specific for each receptor. The proportion of expression for these receptors in the epithelial cells of the ovary does not change after menopause. The proportion of ovaries with AR positive epithelial cells in patients with cervical

  3. Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem.

    PubMed

    Herrera Moro Chao, D; Argmann, C; Van Eijk, M; Boot, R G; Ottenhoff, R; Van Roomen, C; Foppen, E; Siljee, J E; Unmehopa, U A; Kalsbeek, A; Aerts, J M F G

    2016-01-01

    Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem. PMID:27388805

  4. Uterine gland development begins postnatally and is accompanied by estrogen and progesterone receptor expression in the dog.

    PubMed

    Cooke, P S; Borsdorf, D C; Ekman, G C; Doty, K F; Clark, S G; Dziuk, P J; Bartol, F F

    2012-11-01

    During neonatal and juvenile life, mammalian uteri undergo extensive structural and functional changes, including uterine gland differentiation and development. In sheep and mice, inhibition of neonatal uterine gland development induced by progestin treatment led to a permanent aglandular uterine phenotype and adult infertility, suggesting that this strategy might be useful for sterilizing dogs and other companion animals. The goal of this study was to define temporal patterns of adenogenesis (gland development), cell proliferation, and progesterone and estrogen receptor expression in uteri of neonatal and juvenile dogs as a first step toward determining whether neonatal progestin treatments might be a feasible contraceptive approach in this species. Uteri obtained from puppies at postnatal wk 1, 2, 4, 6, or 8 were evaluated histologically and immunostained for MKI67, a marker of cell proliferation, estrogen receptor-1, and progesterone receptor. Adenogenesis was under way at 1 wk of age, as indicated by the presence of nascent glands beginning to bud from the luminal epithelium, and rapid proliferation of both luminal epithelial and stromal cells. By Week 2, glands were clearly identifiable and proliferation of luminal, glandular, and stromal cells was pronounced. At Week 4, increased numbers of endometrial glands were evident penetrating uterine stroma, even as proliferative activity decreased in all cell compartments as compared with Week 2. Whereas gland development was most advanced at Weeks 6 to 8, luminal, glandular, and stromal proliferation was minimal, indicating that the uterus was nearly mitotically quiescent at this age. Both estrogen receptor-1 and progesterone receptor were expressed consistently in uterine stromal and epithelial cells at all ages examined. In summary, canine uterine adenogenesis was underway by 1 wk of age and prepubertal glandular proliferation was essentially complete by Week 6. These results provided information necessary to

  5. Morphine-induced early delays in wound closure: involvement of sensory neuropeptides and modification of neurokinin receptor expression

    PubMed Central

    Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.

    2014-01-01

    Dose-limiting side effects of centrally-acting opioid drugs have led to the use of topical opioids to reduce the pain associated with chronic cutaneous wounds. However, previous studies indicate that topical morphine application impairs wound healing. This study was designed to elucidate the mechanisms by which morphine delays wound closure. Rats were depleted of sensory neuropeptides by treatment with capsaicin, and full-thickness 4 mm diameter wounds were excised from the intrascapular region. Wounds were treated topically twice daily with 5 mM morphine sulfate, 1 mM substance P, 1 mM neurokinin A, or 5 mM morphine combined with 1 m M substance P or neurokinin A and wound areas assessed. During closure, wound tissue was taken 1, 3, 5, and 8 days post-wounding from control and morphine-treated rats and immunostained for neurokinin receptors and markers for macrophages, myofibroblasts, and vasculature. Results obtained from capsaicin-treated animals demonstrated a significant delay in the early stages of wound contraction that was reversed by neuropeptide application. Treatment of capsaicin-treated rats with topical morphine did not further delay wound closure, suggesting that topical opioids impair wound closure via the inhibition of peripheral neuropeptide release into the healing wound. Morphine application altered neurokinin-1 and neurokinin-2 receptor expression in inflammatory and parenchymal cells essential for wound healing in a cell-specific manner, demonstrating a direct effect of morphine on neurokinin receptor regulation within an array of cells involved in wound healing. These data provide evidence indicating a potentially detrimental effect of topical morphine application on the dynamic wound healing process. PMID:19428329

  6. Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem

    PubMed Central

    Herrera Moro Chao, D.; Argmann, C.; Van Eijk, M.; Boot, R. G.; Ottenhoff, R.; Van Roomen, C.; Foppen, E.; Siljee, J. E.; Unmehopa, U. A.; Kalsbeek, A.; Aerts, J. M. F. G.

    2016-01-01

    Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem. PMID:27388805

  7. Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity

    PubMed Central

    Seoane, Iria V.; Ortiz, Ana M.; Piris, Lorena; Lamana, Amalia; Juarranz, Yasmina; García-Vicuña, Rosario; González-Álvaro, Isidoro; Gomariz, Rosa P.; Martínez, Carmen

    2016-01-01

    Background The vasoactive intestinal peptide (VIP) receptors VPAC1 and VPAC2 mediate anti-inflammatory and immunoregulatory responses in rheumatoid arthritis (RA). Data on the expression of these receptors could complement clinical assessment in the management of RA. Our goal was to investigate the correlation between expression of both receptors and the 28-Joint Disease Activity Score (DAS28) in peripheral blood mononuclear cells (PBMCs) from patients with early arthritis (EA). We also measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation. Methods We analyzed 250 blood samples collected at any of the 5 scheduled follow-up visits from 125 patients enrolled in the Princesa Early Arthritis Register Longitudinal study. Samples from 22 healthy donors were also analyzed. Sociodemographic, clinical, and therapeutic data were systematically recorded. mRNA expression levels were determined using real-time PCR. Then, longitudinal multivariate analyses were performed. Results PBMCs from EA patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p<0.001). With time, however, VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index. Our results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 (p<0.001) and conversely with increased expression of VPAC2 (p<0.001). A major finding of this study is that expression of VPAC1 is lower in patients with increased disease activity (p = 0.001), thus making it possible to differentiate between patients with various degrees of clinical disease activity. Conclusion Patients with more severe inflammation and higher disease activity show lower levels of VPAC1 expression, which is associated with patient-reported impairment. Therefore, VPAC1 is a biological marker in EA. PMID:26881970

  8. Progesterone receptor expression declines in the guinea pig uterus during functional progesterone withdrawal and in response to prostaglandins.

    PubMed

    Welsh, Toni N; Hirst, Jonathan J; Palliser, Hannah; Zakar, Tamas

    2014-01-01

    Progesterone withdrawal is essential for parturition, but the mechanism of this pivotal hormonal change is unclear in women and other mammals that give birth without a pre-labor drop in maternal progesterone levels. One possibility suggested by uterine tissue analyses and cell culture models is that progesterone receptor levels change at term decreasing the progesterone responsiveness of the myometrium, which causes progesterone withdrawal at the functional level and results in estrogen dominance enhancing uterine contractility. In this investigation we have explored whether receptor mediated functional progesterone withdrawal occurs during late pregnancy and labor in vivo. We have also determined whether prostaglandins that induce labor cause functional progesterone withdrawal by altering myometrial progesterone receptor expression. Pregnant guinea pigs were used, since this animal loses progesterone responsiveness at term and gives birth in the presence of high maternal progesterone level similarly to primates. We found that progesterone receptor mRNA and protein A and B expression decreased in the guinea pig uterus during the last third of gestation and in labor. Prostaglandin administration reduced while prostaglandin synthesis inhibitor treatment increased progesterone receptor A protein abundance. Estrogen receptor-1 protein levels remained unchanged during late gestation, in labor and after prostaglandin or prostaglandin synthesis inhibitor administration. Steroid receptor levels were higher in the non-pregnant than in the pregnant uterine horns. We conclude that the decreasing expression of both progesterone receptors A and B is a physiological mechanism of functional progesterone withdrawal in the guinea pig during late pregnancy and in labor. Further, prostaglandins administered exogenously or produced endogenously stimulate labor in part by suppressing uterine progesterone receptor A expression, which may cause functional progesterone withdrawal, promote

  9. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.

    PubMed

    Bravo, Javier A; Forsythe, Paul; Chew, Marianne V; Escaravage, Emily; Savignac, Hélène M; Dinan, Timothy G; Bienenstock, John; Cryan, John F

    2011-09-20

    There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression. PMID:21876150

  10. Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells.

    PubMed

    Jiang, Luning; O'Leary, Claire; Kim, Hyun Ah; Parish, Clare L; Massalas, Jim; Waddington, John L; Ehrlich, Michelle E; Schütz, Günter; Gantois, Ilse; Lawrence, Andrew J; Drago, John

    2015-04-01

    D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIα(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIα(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia. PMID:25684539

  11. Effect of Exercise on µ-Opioid Receptor Expression in the Rostral Ventromedial Medulla in Neuropathic Pain Rat Model

    PubMed Central

    Kim, Young-Jin; Byun, Jeong-Hyun

    2015-01-01

    Objective To investigate the effects of aerobic exercise on neuropathic pain and verify whether regular treadmill exercise alters opioid receptor expression in the rostral ventral medulla (RVM) in a neuropathic pain rat model. Methods Thirty-two male Sprague-Dawley rats were used in the study. All rats were divided into 3 groups, i.e., group A, sham group (n=10); group B, chronic constriction injury (CCI) group (n=11); and group C, CCI+exercise group (n=11). Regular treadmill exercise was performed for 30 minutes a day, 5 days a week, for 4 weeks at the speed of 8 m/min for 5 minutes, 11 m/min for 5 minutes, and 22 m/min for 20 minutes. Withdrawal threshold and withdrawal latency were measured before and after the regular exercise program. Immunohistochemistry and Western blots analyses were performed using antibodies against µ-opioid receptor (MOR). Results Body weight of group C was the lowest among all groups. Withdrawal thresholds and withdrawal latencies were increased with time in groups B and C. There were significant differences of withdrawal thresholds between group B and group C at 1st, 2nd, 3rd, and 4th weeks after exercise. There were significant differences of withdrawal latencies between group B and group C at 3rd and 4th weeks after exercise. MOR expression of group C was significantly decreased, as compared to that of group B in the RVM and spinal cord. Conclusion In neuropathic pain, exercise induced analgesia could be mediated by desensitization of central MOR by endogenous opioids, leading to the shift of RVM circuitry balance to pain inhibition. PMID:26161338

  12. Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood.

    PubMed

    Novick, Andrew M; Mears, Mackenzie; Forster, Gina L; Lei, Yanlin; Tejani-Butt, Shanaz M; Watt, Michael J

    2016-05-01

    Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies. PMID:26876136

  13. Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling.

    PubMed

    Abiega, Oihane; Beccari, Sol; Diaz-Aparicio, Irune; Nadjar, Agnes; Layé, Sophie; Leyrolle, Quentin; Gómez-Nicola, Diego; Domercq, María; Pérez-Samartín, Alberto; Sánchez-Zafra, Víctor; Paris, Iñaki; Valero, Jorge; Savage, Julie C; Hui, Chin-Wai; Tremblay, Marie-Ève; Deudero, Juan J P; Brewster, Amy L; Anderson, Anne E; Zaldumbide, Laura; Galbarriatu, Lara; Marinas, Ainhoa; Vivanco, Maria dM; Matute, Carlos; Maletic-Savatic, Mirjana; Encinas, Juan M; Sierra, Amanda

    2016-05-01

    Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance

  14. Effect of exercise on hyperactivity, impulsivity and dopamine D2 receptor expression in the substantia nigra and striatum of spontaneous hypertensive rats

    PubMed Central

    Cho, Han Sam; Baek, Dae Jung; Baek, Seung Soo

    2014-01-01

    [Purpose] Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurobehavioral disorder that is characterized by hyperactivity, inattention, and impulsivity. It is commonly believed that the symptoms of ADHD are closely associated with hypo-function of the dopamine system. Dopamine D2 receptor activation decreases the excitability of dopamine neurons, as well as the release of dopamine. Physical exercise is known to improve structural and functional impairments in neuropsychiatric disorders. We investigated the therapeutic effect of exercise on ADHD. [Methods] Open field task and elevated-plus maze task were used in the evaluation of hyperactivity and impulsivity, respectively. Dopamine D2 receptor expression in the substantia nigra and striatum were evaluated by western blotting. [Results] The present results indicated that ADHD rats showed hyperactivity and impulsivity. Dopamine D2 receptor expression in the substantia nigra and striatum were increased in ADHD rats. Exercise alleviated hyperactivity and impulsivity in ADHD rats. Furthermore, dopamine D2 receptor expression in ADHD rats was also decreased by exercise. [Conclusion] We thus showed that exercise effectively alleviates ADHD-induced symptoms through enhancing dopamine D2 expression in the brain. PMID:25671205

  15. Tumours of the upper alimentary tract

    PubMed Central

    Head, K. W.

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147

  16. Tumour angiogenesis-Origin of blood vessels.

    PubMed

    Krishna Priya, S; Nagare, R P; Sneha, V S; Sidhanth, C; Bindhya, S; Manasa, P; Ganesan, T S

    2016-08-15

    The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy. PMID:26934471

  17. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver. PMID:26059599

  18. [Pancreatic tumour in a child].

    PubMed

    Schouenborg Schultz, Thea; Thyssen Vestergaard, Esben

    2014-07-28

    Abdominal pain is a common symptom in children and recurrent abdominal pain (RAP) has a prevalence of 8.4% in childhood. In 90-95% of RAPs no organic disease is identified. Thus, it is important that the few of somatic origin are diagnosed. We describe a case concerning a 12-year-old girl, diagnosed with a solid pseudopapillary tumour of the pancreas. The symptoms were RAP and postprandial vomiting. The purpose of this article is to increase the knowledge of "alarm findings" indicating an organic disease in children with RAP. PMID:25292323

  19. The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival.

    PubMed Central

    Veale, D.; Kerr, N.; Gibson, G. J.; Kelly, P. J.; Harris, A. L.

    1993-01-01

    Increased expression of epidermal growth factor receptor (EGFr) has been reported in non small cell lung cancers (NSCLC) when compared to normal lung. We have examined post-operative survival in 19 surgically treated patients with NSCLC who had full characterisation of EGFr on primary tumour membrane preparations from resection specimens. There were ten squamous, seven adeno and two large cell carcinomas. The median concentration of high affinity sites was 31 fmol per mg of protein (4-1532) and the median dissociation constant (Kd) of these high affinity sites was 2.3 x 10(-10) per mol (1.2-30 x 10(-10)). Seven patients survived over 5 years. Twelve patients died between 8.5 and 55 months from the time of surgery. When > 5 year survivors were compared to non-survivors there was no difference as regards tumour size or stage, or as regards age or sex. The survivors had a median concentration of high affinity EGFr sites of 16.1 fmol mg-1 protein compared to a median concentration of 68.6 fmol mg-1 protein in the non-survivors (P = 0.01 Wilcoxon test). No long term survivor had > 35 fmol mg-1 protein of receptor. Thus EGFr quantitation may give independent prognostic information in NSCLC and help to select patients for adjuvant therapy after surgery. These results need confirmation in a larger prospective study. PMID:8391303

  20. Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction.

    PubMed

    Petry, Fernanda S; Dornelles, Arethuza S; Lichtenfels, Martina; Valiati, Fernanda E; de Farias, Caroline Brunetto; Schwartsmann, Gilberto; Parent, Marise B; Roesler, Rafael

    2016-07-01

    Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade. PMID:27025446

  1. Gastrin inhibits a novel, pathological colon cancer signaling pathway involving EGR1, AE2 and P-ERK

    PubMed Central

    Song, Ling-Jun; Liu, Rui-Jun; Zeng, Zhi; Alper, Seth L.; Cui, Heng-Jing; Lu, Yang; Zheng, Lin; Yan, Zhao-Wen; Fu, Guo-Hui

    2016-01-01

    Human anion exchanger 2 (AE2) is a plasma membrane protein that regulates intracellular pH and cell volume. AE2 contributes to transepithelial transport of chloride and bicarbonate in normal colon and other epithelial tissues. We now report that AE2 overexpression in colon cancer cells is correlated with expression of the nuclear proliferation marker, Ki67. Survival analysis of 24 patients with colon cancer in early stage or 33 patients with tubular adenocarcinoma demonstrated that expression of AE2 is correlated with poor prognosis. Cellular and molecular experiments indicated that AE2 expression promoted proliferation of colon cancer cells. In addition, we found that transcription factor EGR1 underlies AE2 upregulation, and the AE2 sequester p16INK4a (P16) in the cytoplasm of colon cancer cells. Cytoplasmic P16 enhanced ERK phosphorylation and promoted proliferation of colon cancer cells. Gastrin inhibited proliferation of colon cancer cells by suppressing expression of EGR1 and AE2 and by blocking ERK phosphorylation. Taken together, our data describe a novel EGR1/AE2/P16/P-ERK signaling pathway in colon carcinogenesis, with implications for pathologic prognosis and for novel therapeutic approaches. PMID:22228178

  2. Electrochemotherapy on liver tumours in rabbits.

    PubMed Central

    Ramirez, L. H.; Orlowski, S.; An, D.; Bindoula, G.; Dzodic, R.; Ardouin, P.; Bognel, C.; Belehradek, J.; Munck, J. N.; Mir, L. M.

    1998-01-01

    Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies. Images Figure 1 Figure 2 PMID:9649121

  3. Transillumination imaging of intraocular tumours.

    PubMed

    Kjersem, Bård; Krohn, Jørgen

    2013-06-01

    The purpose of this paper is to discuss a recently described modification of a standard photo slit lamp system for ocular transillumination, with special emphasis on the light transmission through the eye wall and the photographic technique. Transillumination photography was carried out with the Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG, Koeniz, Switzerland). After having released the background lighting optic fibre cable from its holder, the patient was positioned at the slit lamp, and the fibre tip was gently pressed against the sclera or the cornea of the patient's eye. During about 1/1000 of a second, the eye was illuminated by the flash and the scleral shadow of the tumour was exposed to the camera sensor. The images were of good diagnostic quality, making it easy to outline the tumours and to evaluate the involvement of intraocular structures. None of the examined patients experienced discomfort or negative side effects. The method is recommended in cases where photographic transillumination documentation of intraocular pathologies is considered important. PMID:23641762

  4. Comparative analysis of mineralocorticoid receptor expression among vocal learners (Bengalese finch and budgerigar) and non-vocal learners (quail and ring dove) has implications for the evolution of avian vocal learning.

    PubMed

    Matsunaga, Eiji; Suzuki, Kenta; Kobayashi, Tetsuya; Okanoya, Kazuo

    2011-12-01

    Mineralocorticoid receptor is the receptor for corticosteroids such as corticosterone or aldosterone. Previously, we found that mineralocorticoid receptor was highly expressed in song nuclei of a songbird, Bengalese finch (Lonchura striata var. domestica). Here, to examine the relationship between mineralocorticoid receptor expression and avian vocal learning, we analyzed mineralocorticoid receptor expression in the developing brain of another vocal learner, budgerigar (Melopsittacus undulatus) and non-vocal learners, quail (Coturnix japonica) and ring dove (Streptopelia capicola). Mineralocorticoid receptor showed vocal control area-related expressions in budgerigars as Bengalese finches, whereas no such mineralocorticoid receptor expressions were seen in the telencephalon of non-vocal learners. Thus, these results suggest the possibility that mineralocorticoid receptor plays a role in vocal development of parrots as songbirds and that the acquisition of mineralocorticoid receptor expression is involved in the evolution of avian vocal learning. PMID:22010640

  5. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  6. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  7. Peculiarities of hyperlipidaemia in tumour patients.

    PubMed Central

    Dilman, V. M.; Berstein, L. M.; Ostroumova, M. N.; Tsyrlina, Y. V.; Golubev, A. G.

    1981-01-01

    The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer). PMID:7248149

  8. Classification of odontogenic tumours. A historical review.

    PubMed

    Philipsen, Hans Peter; Reichart, Peter A

    2006-10-01

    Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon. PMID:16968232

  9. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

  10. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

    PubMed Central

    Ince, Tan A.; Sousa, Aurea D.; Jones, Michelle A.; Harrell, J. Chuck; Agoston, Elin S.; Krohn, Marit; Selfors, Laura M.; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S.; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T.; Merritt, Melissa A.; Foster, Rosemary; Rueda, Bo R.; Crum, Christopher P.; Brugge, Joan S.; Mills, Gordon B.

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  11. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours.

    PubMed

    Ince, Tan A; Sousa, Aurea D; Jones, Michelle A; Harrell, J Chuck; Agoston, Elin S; Krohn, Marit; Selfors, Laura M; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T; Merritt, Melissa A; Foster, Rosemary; Rueda, Bo R; Crum, Christopher P; Brugge, Joan S; Mills, Gordon B

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  12. Sex- and age-specific differences in relaxin family peptide receptor expression within the hippocampus and amygdala in rats.

    PubMed

    Meadows, K L; Byrnes, E M

    2015-01-22

    Relaxin is an essential pregnancy-related hormone with broad peripheral effects mediated by activation of relaxin-like family peptide 1 receptors (RXFP1). More recent studies suggest an additional role for relaxin as a neuropeptide, with RXFP1 receptors expressed in numerous brain regions. Neurons in an area of the brainstem known as the nucleus incertus (NI) produce relaxin 3 (RLN3), the most recently identified neuropeptide in the relaxin family. RLN3 has been shown to activate both RXFP1 and relaxin-like family peptide receptor 3 (RXFP3) receptor subtypes. Studies suggest wide-ranging neuromodulatory effects of both RXFP1 and RXFP3 activation, although to date the majority of studies have been conducted in young males. In the current study, we examined potential sex- and age-related changes in RLN3 gene expression in the NI as well as RXFP1 and RXFP3 gene expression in the dorsal hippocampus (HI), ventral hippocampus (vHI) and amygdala (AMYG) using young adult (9-12weeks) and middle-aged (9-12months) male and female rats. In addition, regional changes in RXFP1 and RXFP3 protein expression were examined in the CA1, CA2/CA3 and dentate gyrus (DG) as well as within basolateral (BLA), central (CeA), and medial (MeA) amygdaloid nuclei. In the NI, RLN3 showed an age-related decrease in males. In the HI, only the RXFP3 receptor showed an age-related change in gene expression, however, both receptor subtypes showed age-related changes in protein expression that were region specific. Additionally, while gene and protein expression of both receptors increased with age in AMYG, these effects were both region- and sex-specific. Finally, overall males displayed a greater number of cells that express the RXFP3 protein in all of the amygdaloid nuclei examined. Cognitive and emotional processes regulated by activity within the HI and AMYG are modulated by both sex and age. The vast majority of studies exploring the influence of sex on age-related changes in the HI and AMYG have

  13. Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.

    PubMed

    Wang, Yan; Ma, Yuchao; Hu, Jingmin; Zhang, Xinxin; Cheng, Wenwen; Jiang, Han; Li, Min; Ren, Jintao; Zhang, Xiaosong; Liu, Mengxi; Sun, Anji; Wang, Qi; Li, Xiaobai

    2016-07-01

    Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress. PMID:27094122

  14. Analgesic tolerance of opioid agonists in mutant mu-opioid receptors expressed in sensory neurons following intrathecal plasmid gene delivery

    PubMed Central

    2013-01-01

    Background Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo. To facilitate the determination of the contribution of phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed mutant and wild-type human MORs (hMORs) in sensory dorsal root ganglion (DRG) neurons, a major site for nociceptive (pain) signaling and determined morphine- and the full MOR agonist, DAMGO,-induced effects on heat-induced hyperalgesic behaviors and potassium current (IK) desensitization in these rats. Findings A mutant hMOR DNA with the putative phosphorylation threonine site at position 394 replaced by an alanine (T394A), i.e., hMOR-T, or a plasmid containing wild type hMOR (as a positive control) was intrathecally delivered. The plasmid containing GFP or saline was used as the negative control. To limit the expression of exogenous DNA to neurons of DRGs, a neuron-specific promoter was included in the plasmid. Following a plasmid injection, hMOR-T or hMOR receptors were expressed in small and medium DRG neurons. Compared with saline or GFP rats, the analgesic potency of morphine was increased to a similar extent in hMOR-T and hMOR rats. Morphine induced minimum IK desensitization in both rat groups. In contrast, DAMGO increased analgesic potency and elicited IK desensitization to a significantly less extent in hMOR-T than in hMOR rats. The development and extent of acute and chronic tolerance induced by repeated morphine or DAMGO applications were not altered by the T394A mutation. Conclusions These results indicate that phosphorylation of T394

  15. Myoepithelial cells in canine mammary tumours.

    PubMed

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  16. Transurethral resection and degeneration of bladder tumour

    PubMed Central

    Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

    2013-01-01

    Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

  17. [34 epibulbar malignant tumours (author's transl)].

    PubMed

    Schwartzenberg, T; Vancea, P P; Dobrescu, G

    1979-02-01

    Based on a study of 34 cases, the authors make therapeutical and diagnostical references concerning the epibulbar malignant tumours. These were met with a frequency of 10% of the total amount of the malignant tumours of the visual apparatus. The most frequent setting were at the level of the bulbar conjunctiva and of the sclero-corneal limb, especially in front of the opening of the palpebral slit and in the temporal area. The histological examination of the tumours pointed out the following morphological types; epitheliomas (61%), especially spino-cellular, malignant melanomas (32%) and sarcomas (6%). The therapeutical attitude was the surgical one -- the accurate extirpation -- in the limited tumours, followed by radiotherapy when neoplasic lesions were found at the limit of section. In the invaded tumours, the exenteration of the orbit was performed followed by radiotherapy. On the terms of such a therapeutical conduct, the distant prognosis proved to be dependent on two factors: a. The early diagnosis, that is the stage of the therapeutical action. It is insisted upon the importance of the signs of malignization of some benign tumors: papillomas or naevi. b. The nature and origin of the tumour: the secondary tumours are more severe from the beginning. PMID:444115

  18. The Laser Treatment of Experimental Malignant Tumours

    PubMed Central

    McGuff, Paul E.; Deterling, Ralph A.; Gottlieb, Leonard S.; Fahimi, H. Dariush; Bushnell, David; Roeber, Fred

    1964-01-01

    Some of the results of experiments performed during the past two years to assess effects of laser energy on experimental malignant tumours are reviewed. Twenty types of malignant tumours (most in the cheek pouch and 11 of human origin) were treated in over 700 Syrian hamsters. Results of laser treatment of malignant melanomas and thyroidal carcinomas are presented. A human patient with malignant melanoma treated by laser energy is described. Investigation of thermal effect revealed that the laser-treated tumour remained warm for about one minute, while the cautery-treated tumour cooled to normal temperature in five seconds. Direct action of laser on superficial tumours is possible; deeper lesions must be exposed surgically. Laser energy has a selective effect on certain malignant tumours, resulting in their progressive regression and ultimate dissolution. All hamsters with implanted malignant melanomas and carcinomas of human origin, after completion of a course of laser treatment, showed no gross or histologic evidence of tumour up to the date of last observation. ImagesFig. 1Fig. 2aFig. 2bFig. 2cFig. 2dFig. 2eFig. 2fFig. 3Fig. 4aFig. 4bFig. 4cFig. 4dFig. 4eFig. 4fFig. 4gFig. 6 PMID:14229757

  19. Phase congruency map driven brain tumour segmentation

    NASA Astrophysics Data System (ADS)

    Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

    2015-03-01

    Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

  20. Malignant sweat gland tumours: an update.

    PubMed

    Cardoso, José C; Calonje, Eduardo

    2015-11-01

    Cutaneous adnexal tumours can be a diagnostic challenge for the pathologist. This is particularly true in the case of tumours with sweat gland differentiation, due to a large number of rare entities, a multiplicity of names to designate the same neoplasms and consequent lack of consensus regarding their classification and nomenclature. In the traditional view, sweat gland tumours were divided into eccrine and apocrine. However, this has been challenged in recent years, and in fact many of these tumours may have both eccrine and apocrine variants. Some display more complex features and defy classification, due to the presence of other lines of differentiation, namely follicular and/or sebaceous (in the case of apocrine tumours, due to the close embryological relationship between apocrine glands, hair follicles and sebaceous glands). The present paper reviews and updates the basic concepts regarding the following malignant sweat gland tumours: apocrine carcinoma, porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and primary cutaneous signet ring cell carcinoma. Particular emphasis is put in recent findings that may have implications in the diagnosis and management of these tumours. PMID:26114606

  1. Telomerase activity in 144 brain tumours.

    PubMed Central

    Sano, T.; Asai, A.; Mishima, K.; Fujimaki, T.; Kirino, T.

    1998-01-01

    Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of each specimen to that of human glioma cell line T98G to obtain the relative telomerase activity. Telomerase activity was also assessed visually from the autoradiograms as being positive or negative. One hundred and sixteen tumours with negative telomerase activity had null relative telomerase activity, whereas 28 tumours with positive telomerase activity had relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P < 0.0001). Thus, quantification of telomerase activity confirmed the results of the visual evaluation of telomerase activity on autoradiograms. Based on the assessment, malignant brain tumours had a higher positive rate of telomerase activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that positive telomerase activity is strongly associated with malignant brain tumours and is rather rare in benign tumours, such as neurinomas or meningiomas. Images Figure 2 PMID:9635839

  2. A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice.

    PubMed

    Couch, Yvonne; Xie, Qin; Lundberg, Louise; Sharp, Trevor; Anthony, Daniel C

    2015-01-01

    It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5 mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours post-injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS. PMID:26147001

  3. Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain.

    PubMed

    Torres, Elisa; Gutierrez-Lopez, Maria Dolores; Borcel, Erika; Peraile, Ines; Mayado, Andrea; O'Shea, Esther; Colado, Maria Isabel

    2010-04-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') produces selective long-lasting serotonergic neurotoxicity in rats. The drug also produces acute hyperthermia which modulates the severity of the neurotoxic response. In addition, MDMA produces signs of neuroinflammation reflected as microglial activation and an increase in the release of interleukin-1beta, the latter of which appears to be a consequence of the hyperthermic response and to be implicated in the neurotoxicity induced by the drug. Over-expression of the cannabinoid CB2 receptor in microglia during non-immune and immune pathological conditions is thought to be aimed at controlling the production of neurotoxic factors such as proinflammatory cytokines. Our objective was to study the pattern of CB2 receptor expression following MDMA and to examine the effect of JWH-015 (a CB2 agonist) on the MDMA-induced neuroinflammatory response as well as 5-hydroxytryptamine (5-HT) neurotoxicity. Adult Dark Agouti rats were given MDMA (12.5 mg/kg, i.p.) and killed 3 h or 24 h later for the determination of CB2 receptor expression. JWH-015 was given 48 h, 24 h and 0.5 h before MDMA and 1 h and/or 6 h later and animals were killed for the determination of microglial activation (3 h and 24 h) and 5-HT neurotoxicity (7 days). MDMA increased CB2 receptor expression shortly after administration and these receptors were found in microglia. JWH-015 decreased MDMA-induced microglial activation and interleukin-1beta release and slightly decreased MDMA-induced 5-HT neurotoxicity. In conclusion, CB2 receptor activation reduces the neuroinflammatory response following MDMA and provides partial neuroprotection against the drug. PMID:20067581

  4. A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice

    PubMed Central

    Couch, Yvonne; Xie, Qin; Lundberg, Louise; Sharp, Trevor; Anthony, Daniel C.

    2015-01-01

    It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours post-injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS. PMID:26147001

  5. Gastrin-Releasing Peptide Signaling Plays a Limited and Subtle Role in Amygdala Physiology and Aversive Memory

    PubMed Central

    Chaperon, Frederique; Fendt, Markus; Kelly, Peter H.; Lingenhoehl, Kurt; Mosbacher, Johannes; Olpe, Hans-Rudolf; Schmid, Peter; Sturchler, Christine; McAllister, Kevin H.; van der Putten, P. Herman; Gee, Christine E.

    2012-01-01

    Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe6, Leu-NHEt13, des-Met14)-Bombesin (6–14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders. PMID:22509372

  6. Hypothalamic gastrin-releasing peptide receptor mediates an antidepressant-like effect in a mouse model of stress

    PubMed Central

    Yao, Lihua; Chen, Jianxin; Chen, Hexiang; Xiang, Dan; Yang, Can; Xiao, Ling; Liu, Wanhong; Wang, Huiling; Wang, Gaohua; Zhu, Fan; Liu, Zhongchun

    2016-01-01

    Evidence has shown that gastrin-releasing peptide receptor (GRPR) is involved in responses to stress and anxiety. The primary role of GRPR is to stimulate corticotrophin-releasing hormone (CRH) or adrenocorticotropic hormone (ACTH) secretion. Thus, the mechanisms of GRPR signaling should be elucidated to discover novel therapeutic targets for treating depression. This study aimed to investigate GRPR alterations in the C57 mouse hypothalamus after the animals were subjected to stress and fluoxetine treatments. Specifically, we subjected the mice to isolation and chronic unpredictable mild stress (CUMS) for three weeks to establish an experimental model of depression. These mice were subsequently treated with fluoxetine for three weeks. Then, we performed the sucrose preference test and the open field test and measured food intake and body weight to explore the effects of stress and fluoxetine on activity and anhedonia. After fluoxetine treatment, we also assessed changes in the levels of GRPR expression in the hypothalamus using immunohistochemistry, western blotting, and real-time quantitative PCR (RT-PCR). We found that stressed mice showed significant reductions in locomotion, food intake/body weight, and sucrose preference; these reduced parameters indicated a state of anhedonia. Marked increases in mRNA and protein expression of GRPR in the hypothalamus of CUMS-exposed mice were also observed, although treatment with fluoxetine reversed these stress-induced changes. Our results also demonstrated the feasibility and effectiveness of the C57 mouse model of depression established by CUMS and isolation. After fluoxetine treatment was administered, the animals’ depression symptoms were alleviated, and these behavioral alterations were accompanied by specific changes in mRNA and protein expression of GRPR in the hypothalamus. These results suggest that GRPR may be implicated in depression; therefore, new therapeutic targets of depression focused on GRPR signaling

  7. Hypothalamic gastrin-releasing peptide receptor mediates an antidepressant-like effect in a mouse model of stress.

    PubMed

    Yao, Lihua; Chen, Jianxin; Chen, Hexiang; Xiang, Dan; Yang, Can; Xiao, Ling; Liu, Wanhong; Wang, Huiling; Wang, Gaohua; Zhu, Fan; Liu, Zhongchun

    2016-01-01

    Evidence has shown that gastrin-releasing peptide receptor (GRPR) is involved in responses to stress and anxiety. The primary role of GRPR is to stimulate corticotrophin-releasing hormone (CRH) or adrenocorticotropic hormone (ACTH) secretion. Thus, the mechanisms of GRPR signaling should be elucidated to discover novel therapeutic targets for treating depression. This study aimed to investigate GRPR alterations in the C57 mouse hypothalamus after the animals were subjected to stress and fluoxetine treatments. Specifically, we subjected the mice to isolation and chronic unpredictable mild stress (CUMS) for three weeks to establish an experimental model of depression. These mice were subsequently treated with fluoxetine for three weeks. Then, we performed the sucrose preference test and the open field test and measured food intake and body weight to explore the effects of stress and fluoxetine on activity and anhedonia. After fluoxetine treatment, we also assessed changes in the levels of GRPR expression in the hypothalamus using immunohistochemistry, western blotting, and real-time quantitative PCR (RT-PCR). We found that stressed mice showed significant reductions in locomotion, food intake/body weight, and sucrose preference; these reduced parameters indicated a state of anhedonia. Marked increases in mRNA and protein expression of GRPR in the hypothalamus of CUMS-exposed mice were also observed, although treatment with fluoxetine reversed these stress-induced changes. Our results also demonstrated the feasibility and effectiveness of the C57 mouse model of depression established by CUMS and isolation. After fluoxetine treatment was administered, the animals' depression symptoms were alleviated, and these behavioral alterations were accompanied by specific changes in mRNA and protein expression of GRPR in the hypothalamus. These results suggest that GRPR may be implicated in depression; therefore, new therapeutic targets of depression focused on GRPR signaling

  8. FUNCTION OF NON-VISUAL ARRESTINS IN SIGNALING AND ENDOCYTOSIS OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR (GRP RECEPTOR)

    PubMed Central

    Schumann, Michael; Nakagawa, Tomoo; Mantey, Samuel A.; Howell, Brian; Jensen, Robert T.

    2008-01-01

    Little is known about the role of arrestins in gastrointestinal hormone/neurotransmitter receptor endocytosis. With other G protein-coupled receptors, arrestins induce G protein-uncoupling and receptor endocytosis. In this study, we used arrestin wild-type and dominant-negative mutant constructs to analyze the arrestin dependence of endocytosis and desensitization of the gastrin- releasing peptide receptor (GRP-R). Co-expression of the GRP-R with wild-type arrestin-2 and arrestin-3 increased not only GRP-R endocytosis but also GRP-R desensitization in arrestin-overexpressing cells. Co-expression of the dominant-negative mutants V53D-arrestin-2 or V54D-arrestin-3 reduced GRP-R endocytosis. Notably, different trafficking routes for agonist-activated GRPR-arrestin-2 and GRPR-arrestin-3 complexes were found. Arrestin-3 internalizes with GRP-R to intracellular vesicles, arrestin-2 splits from the GRP-R and localizes to the cell membrane. Also, the recycling pathway of the GRP-R was different if co-expressed with arrestin-2 or arrestin-3. Using different GRP-R mutants, the C-terminus and the 2nd intracellular loop of the GRP-R were found to be important for the GRPR-arrestin interaction and for the difference in GRP receptor trafficking with the two arrestin subtypes. Our results show that both non-visual arrestins play an important role in GRP-R internalization and desensitization. PMID:18199425

  9. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    PubMed

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. PMID:26658172

  10. Appendiceal tumour--retrospective clinicopathological analysis.

    PubMed

    Machado, Norman O'Neil; Chopra, Pradeep; Pande, Girish

    2004-01-01

    Appendiceal tumours are rare and often discovered unexpectedly in an acute situation in which decision-making is difficult. We report the spectrum of appendiuar tumours seen in our institution over a period of more than 10 years, and discuss the clinicopathological behaviour, investigations, surgical procedures and outcomes in these patients. We have also reviewed the literature with regard to appendiceal tumours. Appendicular tumours were identified from the database of 1646 appendictomies (18% in children) performed in single centre and case notes were reviewed. Clinical presentation, investigations, histopathology, surgical procedures and outcome were analysed. Twelve patients with appendiceal tumours were identified (0.72%): 8 carcinoid, 2 mucinous (mucocele) and 2 adenocarcinoma. All the patients with a carcinoid tumour presented with features suggestive of acute appendicitis and were diagnosed postoperatively following appendicectomy and formal histology. No further surgical intervention was required as these lesions were less than 1cm away from the base of the appendix. One of the patient with mucinous cystadenoma presented acutely and underwent an appendicectomy; in the other patient with chronic pain, apreoperative MRI suggested the diagnosis leading to a planned hemicolectomy as the lesion was close to the base of the appendix. While one of the patient with an adenocarcinoma localized to the appendix did well following a right hemicolectomy, the other patient with disseminated disease succumbed within a year. Carcinoid tumours are the commonest appendiceal tumours, which present often as acute appendicitis. While appendicectomy would be adequate in most of these patients, in patients with a cystadenoma close to the base of the appendix or in case of a carcinoma, a right hemicolectomy is the appropriate option. While the prognosis is good in patients with carcinoid tumour and cystadenoma, it remains dismal in patients with disseminated malignant disease

  11. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour

    PubMed Central

    Valarmathi, K.; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-01-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  12. Photodynamic therapy and anti-tumour immunity

    PubMed Central

    Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  13. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour.

    PubMed

    Devi, Nalli R Sumitra; Valarmathi, K; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-02-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  14. The prophylaxis of nonindustrial urothelial tumours

    PubMed Central

    Mount, Balfour M.

    1973-01-01

    Present knowledge concerning carcinogenesis and the natural history of urothelial tumours precludes firm conclusions relative to nonindustrial prophylaxis. However, a number of measures are consistent with current data and may be instituted for those patients with a demonstrated propensity to urothelial tumours. Their acceptability is based on the lack of associated toxicity for the patient. These measures include the elimination of significant infection, cigarettes, artificial sweeteners, analgesic abuse and coffee, the administration of vitamins C and B6, and in selected cases, the use of thiotepa. It is emphasized that the merit of these steps in altering the natural history of urothelial tumours is uncertain. PMID:4197537

  15. Growth factors, their receptor expression and markers for proliferation of endothelial and neoplastic cells in human osteosarcoma.

    PubMed

    Bianchi, E; Artico, M; Di Cristofano, C; Leopizzi, M; Taurone, S; Pucci, M; Gobbi, P; Mignini, F; Petrozza, V; Pindinello, I; Conconi, M T; Della Rocca, C

    2013-01-01

    Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF - TrKA - NT3 - TrKC - VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-beta was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation. PMID:24067459

  16. [Clinical types of thoracic cancer. Mediastinal tumours].

    PubMed

    Lemarié, E

    2006-11-01

    Mediastinal germ cell tumours (teratomas, seminomas, and non-seminomatous malignant germ cell tumours) are a heterogeneous group of benign and malignant neoplasms. The standard treatment of mediastinal non-seminomatous malignant germ cell tumours is four cycles of chemotherapy followed by surgical resection of the residual mass. Small localized mediastinal seminomas may be treated with primary resection followed by radiotherapy. In patients with locally advanced disease, the preferred treatment is systemic chemotherapy followed by surgical resection of any residual disease. Thymomas can be locally invasive and associated with parathymic syndromes. Complete surgical excision is attempted in most cases of thymoma. Radiation therapy is usually recommended for invasive or incompletely excised tumours. Invasive thymoma is chemosensitive. PMID:17268355

  17. A rare solitary fibrous tumour of kidney.

    PubMed

    Pathak, Tilak Bahadur; Nepal, Umesh

    2013-01-01

    A solitary fibrous tumour is an unusual spindle cell neoplasm. It frequently arises from the serosal surface of pleural cavity but has recently been described in diverse extrapleural sites. Urogenital localization is rare and only 36 cases of solitary fibrous tumours of the kidney have been described on published report. We report a case of a large solitary fibrous tumour clinically and radiologically thought to be renal cell carcinoma arising in the kidney of a 30 year old female. The radical nephrectomy was performed. The tumour was a well- circumscribed, solid mass attached to the renal pelvis without necrosis and haemorrhage. Histopathologically, a spindle cell neoplasia with alternating hypo and hypercellular areas, storiform, fascicular and hemangipericytoma like growth pattern and less cellular dense collagen deposits were observed. Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2 protein. PMID:24362666

  18. Dentigerous Cyst Associated with Adenomatoid Odontogenic Tumour

    PubMed Central

    Majumdar, Sumit; Uppala, Divya; Talasila, Sunil; Babu, Mahesh

    2015-01-01

    Adenomatoid odontogenic tumour (AOT), a tumour composed of odontogenic epithelium, is an uncommon tumour of odontogenic origin that accounts for only 2.2- 7.1% of all odontogenic tumours. Very few cases of AOT associated with Dentigerous cyst (DC) have been reported till date, most cases are in females and have a striking tendency to occur in the anterior maxilla. The present case is that of a 14-year-old female who revealed a large radiolucent lesion associated with the crown of an unerupted canine located in the left maxillary anterior region. The microscopic examination revealed the presence of AOT in the fibrous capsule of a DC. In this paper, we describe the importance of grossing, sectioning and complete examination of the slide to diagnose such hybrid lesions. PMID:26155575

  19. Primary malignant tumours of the duodenum.

    PubMed

    Nix, G A; Wilson, J H; Dees, J

    1985-04-01

    The clinical and radiological findings in 19 patients with primary duodenal malignancy are described. Weight loss, abdominal pain, nausea and vomiting were the main symptoms. Diagnosis was made by endoscopy or ERCP (71%) or by barium studies (68%). In retrospect the tumour was visible in 97% of the studies. Tumour growth was longitudinal, circular or spiral, the inner curvature being involved over a greater length than the outer curvature. Exophytic tumour growth, involvement of the papilla of Vater, malignant spikes, transient, non-constant tumour image, skip lesions and ulceration were often seen. Mean survival time was 18 months from start of symptoms in 10 inoperable patients, and 24 months in 9 patients undergoing resection. PMID:2986213

  20. Chemotherapy sensitivity testing in human tumours.

    PubMed Central

    Richmond, H G; Billington, R W

    1981-01-01

    We have attempted to establish in vitro growth in a consecutive series of 245 malignant tumours submitted for routine histopathology. Initially, three disaggregation procedures were used: mechanical separation, digestion by trypsin, and digestion by collagenase. The resulting cell fractions had varying success rates in establishing growth. Abundant epithelial cell growth was achieved in monolayer culture in 63 tumours, and the sensitivity of the cells to cytotoxic agents was tested. There was no indiscriminate cytotoxic effect, and each tumour type varied in its sensitivity from one patient's lesion to another. While testing of all solid tumours is not possible with present-day techniques, we believe that the employment of in vitro sensitivity testing as a routine procedure may be possible in the future if a suitable system giving correlation between in vitro and in vivo sensitivity can be developed. Images PMID:7240421

  1. The International Histological Classification of Tumours*

    PubMed Central

    Sobin, L. H.

    1981-01-01

    This article reviews the development of the WHO project on the histological classification of tumours, which has included the establishment of several collaborating centres and has involved more than 300 pathologists in over 50 countries. The project has resulted in the publication, over the last 14 years, of 25 volumes in the first series of the International Histological Classification of Tumours (IHCT), each giving a classification of tumours specific to a certain site. The classifications are based primarily on the microscopic characteristics of the tumours and are concerned with morphologically identifiable cell types and histological patterns as seen by means of light microscopy and conventional staining techniques. The article also describes the relationship between IHCT and other classification and coding systems and assesses possible future developments that may result from new approaches to diagnosis. PMID:6978190

  2. Imaging tumour hypoxia with positron emission tomography

    PubMed Central

    Fleming, I N; Manavaki, R; Blower, P J; West, C; Williams, K J; Harris, A L; Domarkas, J; Lord, S; Baldry, C; Gilbert, F J

    2015-01-01

    Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers. PMID:25514380

  3. Intramuscular Hibernoma: A Rare Tumour in Buttock

    PubMed Central

    Naik, Reena; Kushwaha, Anil KU; Agrawal, P.C.

    2015-01-01

    Hibernomas are benign tumours of brown fat that does not recur after complete excision. These tumours are found most often in adults and most commonly in thigh. Four morphologic variants of hibernoma are identified: typical, myxoid, spindle cell, and lipoma-like. The most common histologic type is typical variant. In this report, we present the clinical, morphological features and discuss the differential diagnosis of a typical variant of intramuscular hibernoma. PMID:26266129

  4. Antenatally detected solid tumour of kidney

    PubMed Central

    Panda, Shasanka Shekhar; Mandelia, Ankur; Gupta, Devendra Kumar; Singh, Amit

    2014-01-01

    Congenital renal tumours are rare and usually benign. Polyhydramnios is the most common mode of presentation. Although most cases have been diagnosed postnatally, with advances in imaging technology, an increasing number of cases are being detected on antenatal scans. We describe a case of solid tumour of kidney detected in the second trimester of pregnancy and managed by surgery in the postnatal period. PMID:24526198

  5. Skull metastasis from rectal gastrointestinal stromal tumours.

    PubMed

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach. PMID:19776004

  6. Epithelial odontogenic tumours in domestic animals.

    PubMed

    Walsh, K M; Denholm, L J; Cooper, B J

    1987-09-01

    Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog. PMID:3316314

  7. Treadmill exercise inhibits hippocampal apoptosis through enhancing N-methyl-D-aspartate receptor expression in the MK-801-induced schizophrenic mice

    PubMed Central

    Chung, Jin Woo; Seo, Jin-Hee; Baek, Sang-Bin; Kim, Chang-Ju; Kim, Tae-Woon

    2014-01-01

    Schizophrenia is a severe mental disorder characterized by abnormal mental functioning and disruptive behaviors. Abnormal expression of N-methyl-D-aspartate (NMDA) receptor, one of the glutamate receptor subtypes, has also been suggested to contribute to the symptoms of schizophrenia. The effect of treadmill exercise on schizophrenia-induced apoptosis in relation with NMDA receptor has not been evaluated. In the present study, we investigated the effect of treadmill exercise on neuronal apoptosis in the hippocampus using MK-801-induced schizophrenic mice. MK-801 was intraperitoneally injected once a day for 2 weeks. The mice in the exercise groups were forced to run on a treadmill exercise for 60 min, once a day for 2 weeks. In the present results, repeated injection of the NMDA receptor antagonist MK-801 reduced expression of NMDA receptor in hippocampal CA2-3 regions. MK-801 injection increased casapse-3 expression and enhanced cytochrome c release in the hippocampus. The ratio of Bax to Bcl-2 was higher in the MK-801-induced schizophrenia mice than the normal mice. In contrast, treadmill exercise enhanced NMDA receptor expression, suppressed caspae-3 activation and cytochrome c release, and inhibited the ratio of Bax to Bcl-2. Based on present finding, we concluded that NMDA receptor hypofunctioning induced neuronal apoptosis in MK-801-induced schizophrenic mice. Treadmill exercise suppressed neuronal apoptosis through enhancing NMDA receptor expression in schizophrenic mice. PMID:25210696

  8. Vitamin D3 supplementation increases insulin level by regulating altered IP3 and AMPA receptor expression in the pancreatic islets of streptozotocin-induced diabetic rat.

    PubMed

    Jayanarayanan, Sadanandan; Anju, Thoppil R; Smijin, Soman; Paulose, Cheramadathikudiyil Skaria

    2015-10-01

    Pancreatic islets, particularly insulin-secreting β cells, share common characteristics with neurons. Glutamate is one of the major excitatory neurotransmitter in the brain and pancreas, and its action is mediated through glutamate receptors. In the present work, we analysed the role of vitamin D3 in the modulation of AMPA receptor subunit and their functional role in insulin release. Radio receptor binding study in diabetic rats showed a significant increase in AMPA receptor density. Insulin AMPA colabelling study showed an altered AMPA GluR2 and GluR4 subunit expression in the pancreatic beta cells. We also found lowered IP3 content and decreased IP3 receptor in pancreas of diabetic rats. The alterations in AMPA and IP3 receptor resulted in reduced cytosolic calcium level concentration, which further blocks Ca(2+)-mediated insulin release. Vitamin D3 supplementation restored the alteration in vitamin D receptor expression, AMPA receptor density and AMPA and IP3 receptor expression in the pancreatic islets that helps to restore the calcium-mediated insulin secretion. Our study reveals the antidiabetic property of vitamin D3 that is suggested to have therapeutic role through regulating glutamatergic function in diabetic rats. PMID:26054778

  9. Gold nanoprobes-based resonance Rayleigh scattering assay platform: Sensitive cytosensing of breast cancer cells and facile monitoring of folate receptor expression.

    PubMed

    Cai, Huai-Hong; Pi, Jiang; Lin, Xiaoying; Li, Baole; Li, Aiqun; Yang, Pei-Hui; Cai, Jiye

    2015-12-15

    A rapid, facile assay for sensitive cytosensing of breast cancer cells should help to guide potential medical evaluation for breast cancer. Here, we report development of novel resonance Rayleigh scattering (RRS) cytosensor for cell recognitions and folate (FA) receptor expression analyses on living cells. Using FA-conjugated gold nanoparticles (FA-AuNPs) as nanoprobes, the constructed nanoprobes-assembled recognition interface could increase the binding capacity for cell recognition, amplify Au-aggregates-enhanced RRS signal, and then enhance the sensitivity for membrane antibody assay. FA-AuNPs-based RRS measurements enabled a distinct 34-times-enhancement in RRS intensities after incubation with human breast cancer cells, compared with normal cells. Receptor-targeted cytosensor was used to quantitatively detect human breast cancer MCF-7, liver cancer HepG2 and normal cells, which expressing different amount of FA receptor, respectively. The detection limit for MCF-7 cells was 12 cells/mL with good selectivity and reproducibility. Furthermore, the proposed cytosensor allowed for dynamic evaluation of FA receptor expression on different living cells after dihydroartemisinin stimulus. This assay platform shows the good potential for clinical diagnostics and antibody-targeted drug screening. PMID:26141102

  10. Pesticide exposure during pregnancy, like nicotine, affects the brainstem α7 nicotinic acetylcholine receptor expression, increasing the risk of sudden unexplained perinatal death.

    PubMed

    Lavezzi, Anna Maria; Cappiello, Achille; Pusiol, Teresa; Corna, Melissa Felicita; Termopoli, Veronica; Matturri, Luigi

    2015-01-15

    This study indicates the impact of nicotine and pesticides (organochlorine and organophosphate insecticides used in agriculture) on neuronal α7-nicotinic acetylcholine receptor expression in brainstem regions receiving cholinergic projections in human perinatal life. An in-depth anatomopathological examination of the autonomic nervous system and immunohistochemistry to analyze the α7-nicotinic acetylcholine receptor expression in the brainstem from 44 fetuses and newborns were performed. In addition, the presence of selected agricultural pesticides in cerebral cortex samples of the victims was determined by specific analytical procedures. Hypodevelopment of brainstem structures checking the vital functions, frequently associated with α7-nicotinic acetylcholine receptor immunopositivity and smoke absorption in pregnancy, was observed in high percentages of victims of sudden unexpected perinatal death. In nearly 30% of cases however the mothers never smoked, but lived in rural areas. The search for pesticides highlighted in many of these cases traces of both organochlorine and organophosphate pesticides. We detain that exposition to pesticides in pregnancy produces homologous actions to those of nicotine on neuronal α7-nicotinic acetylcholine receptor, allowing to developmental alterations of brainstem vital centers in victims of sudden unexplained death. PMID:25433450

  11. Seasonal changes in morphology and steroid receptor expression in the prostate of the brushtail possum (Trichosurus vulpecula): an animal model for the study of prostate growth?

    PubMed

    Martyn, Helen; Pugazhenthi, Kamali; Gould, Maree; Fink, Jo W; McLeod, Bernie; Nicholson, Helen D

    2011-01-01

    The prostate of the brushtail possum undergoes growth and regression during the year. The present study investigated the morphological changes and expression of androgen and oestrogen receptors during the breeding and non-breeding seasons. Prostate tissue was collected from adult possums at 2-monthly intervals. The periurethral and outer glandular areas were separated and the volume of stromal, epithelial and luminal tissues measured in each area. Immunohistochemistry was used to investigate cell proliferation with proliferating cell nuclear antigen (PCNA) and to localise androgen receptor (AR) and oestrogen receptors α and β (ERα, ERβ). Seasonal changes in expression of the three receptors were investigated using quantitative PCR and western blot analysis. During the breeding season the volume of stromal tissue in the periurethral area and the luminal volume in the glandular area significantly increased. The change in periurethral volume was associated with increased PCNA-immunopositive cells. While the localisation of AR to the stromal and epithelial cells did not change, there was a significant increase in receptor expression before the main breeding season. ERα and ERβ expression and localisation did not alter during the year. Similarities in receptor expression and localisation suggest that the possum may be a suitable animal model for the study of human prostate growth. PMID:21635819

  12. Soft Tissue Tumours of the Retroperitoneum

    PubMed Central

    Van Roggen, J. Frans Graadt

    2000-01-01

    Purpose. This review summarizes the more prevalent soft tissue tumours arising in the retroperitoneum and highlights some recent fundamental and diagnostic developments relevant to mesenchymal tumours. Discussion. The retroperitoneum is an underestimated site for benign and malignant neoplastic disease, and represents the second most common site of origin of primary malignant soft tissue tumours (sarcomas) after the deep tissues of the lower extremity. In contrast to the predominance of benign soft tissue lesions over malignant sarcomas elsewhere, retroperitoneal mesenchymal lesions are far more likely to be malignant. The differential diagnosis is primarily with the more common lymphoproliferative and parenchymatous epithelial lesions arising in this area, and with metastatic disease from known or unknown primary sites elsewhere.The most prevalent mesenchymal tumours at this site are of a lipomatous, myogenic or neural nature.Their generally late clinical presentation and poorly accessible location provides numerous clinical challenges; optimal radiological imaging and a properly performed biopsy are essential cogs in the management route. Histopathological diagnosis may be complicated, but has been aided by developments in the fields of immunohistochemistry and tumour (cyto)genetics. Despite significant advances in oncological management protocols, the prognosis remains generally less favourable than for similar tumours at more accessible sites. PMID:18521430

  13. Consensus on biomarkers for neuroendocrine tumour disease

    PubMed Central

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

    2016-01-01

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

  14. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location. PMID:27126667

  15. Ovarian stimulation and granulosa-cell tumour.

    PubMed

    Willemsen, W; Kruitwagen, R; Bastiaans, B; Hanselaar, T; Rolland, R

    1993-04-17

    Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation--ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present. PMID:8096944

  16. Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes.

    PubMed Central

    Versluis, A. J.; Rensen, P. C.; Rump, E. T.; Van Berkel, T. J.; Bijsterbosch, M. K.

    1998-01-01

    Many tumours express relatively high levels of low-density lipoprotein (LDL) receptors on their membranes. The LDL receptor is, therefore, an attractive target for the selective delivery of antineoplastic drugs to tumour cells. We reported previously on the synthesis of small apolipoprotein E (apoE)-containing liposomes that behave in vivo in a very similar way to native LDL. In this study, we examined the interaction of this liposomal carrier with cultured B16 melanoma cells. Binding of apoE liposomes to the cells is saturable, with a maximum binding of approximately 90000 particles per cell. Cross-competition studies indicated that apoE liposomes are bound by the LDL receptor. Association of apoE liposomes to B16 cells is strictly Ca2+ dependent, which forms additional evidence for a role of the LDL receptor. The affinity of apoE liposomes for the LDL receptor on B16 cells is 15-fold higher than that of LDL (0.77 vs 11.5 nM respectively). ApoE is essential for the LDL receptor recognition because liposomes lacking apoE were, in competition studies, 20- to 50-fold less effective than apoE-containing liposomes. We examined in B16 tumour-bearing mice the tumour-localizing properties of apoE liposomes and the disposition of an incorporated lipophilic derivative of daunorubicin (LAD). Tissue distribution studies showed that LAD-loaded apoE liposomes were taken up and processed by the major LDL receptor-expressing organs (i.e. adrenals, liver and spleen). Of all other tissues, the tumour showed the highest uptake. The distribution patterns of LAD-loaded apoE liposomes and native LDL in the tumour-bearing mice were very similar, which supports the role of the LDL receptor in the disposition of the prodrug-loaded particles. The disposition of LAD followed the pattern of the liposomal carrier. We conclude that apoE liposomes enable LDL receptor-mediated specific delivery of antineoplastic (pro)drugs to tumours, and, therefore, constitute an attractive novel option for

  17. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight

    PubMed Central

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-01-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. PMID:25648860

  18. Tumour macrophages as potential targets of bisphosphonates

    PubMed Central

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  19. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    NASA Astrophysics Data System (ADS)

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-02-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

  20. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    PubMed Central

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-01-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID:26861829

  1. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    PubMed Central

    Vijayakumar, Thusyanth; Bakhshinyan, David; Venugopal, Chitra; Singh, Sheila K.

    2015-01-01

    CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs), are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools. PMID:26064134

  2. Tumour resistance to cisplatin: a modelling approach

    NASA Astrophysics Data System (ADS)

    Marcu, L.; Bezak, E.; Olver, I.; van Doorn, T.

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

  3. Tumours and dysplasias of the mammary gland

    PubMed Central

    Hampe, J. F.; Misdorp, W.

    1974-01-01

    As mammary tumours occur frequently in the dog and cat but rarely in other domestic animals, only the tumours of these two species are classified. The epithelial tumours are termed “complex” when they consist of cells resembling both secretory and myoepithelial cells: these tumours are biologically less malignant than tumours of the “simple” type in which only one of these kinds of cell is present. The carcinomas are subdivided into adenocarcinoma, solid carcinoma, spindle cell carcinoma, anaplastic carcinoma, squamous cell carcinoma, and mucinous carcinoma. The term “carcinosarcoma or malignant mixed tumour” was used only when there were cells morphologically resembling not only one or both of the epithelial components but also connective tissue cells with their products of differentiation. The benign tumours are classed as adenoma, papilloma, fibroadenoma, or benign soft tissue tumour. The dysplasias are described under the following headings: cyst, adenosis, regular typical epithelial proliferation in ducts and lobules (epitheliosis), duct ectasia, fibrosclerosis, and lobular hyperplasia. ImagesFig. 41Fig. 42Fig. 43Fig. 44Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 45Fig. 46Fig. 47Fig. 48Fig. 17Fig. 18Fig. 19Fig. 20Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 30Fig. 31Fig. 32Fig. 21Fig. 22Fig. 23Fig. 24Fig. 37Fig. 38Fig. 39Fig. 40Fig. 9Fig. 10Fig. 11Fig. 12Fig. 1Fig. 2Fig. 3Fig. 4Fig. 33Fig. 34Fig. 35Fig. 36 PMID:4371737

  4. Cystic lesions accompanying extra-axial tumours.

    PubMed

    Lohle, P N; Wurzer, H A; Seelen, P J; Kingma, L M; Go, K G

    1999-01-01

    We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2-macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue. PMID:9987761

  5. Naturally occurring tumours in the basal metazoan Hydra.

    PubMed

    Domazet-Lošo, Tomislav; Klimovich, Alexander; Anokhin, Boris; Anton-Erxleben, Friederike; Hamm, Mailin J; Lange, Christina; Bosch, Thomas C G

    2014-01-01

    The molecular nature of tumours is well studied in vertebrates, although their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring tumours in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that most metazoans might be prone to develop tumours. Here we provide first evidence for naturally occurring tumours in two species of Hydra. Histological, cellular and molecular data reveal that these tumours are transplantable and might originate by differentiation arrest of female gametes. Growth of tumour cells is independent from the cellular environment. Tumour-bearing polyps have significantly reduced fitness. In addition, Hydra tumours show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows that spontaneous tumours have deep evolutionary roots and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis. PMID:24957317

  6. Tumour-specific CD4 T cells eradicate melanoma via indirect recognition of tumour-derived antigen.

    PubMed

    Shklovskaya, Elena; Terry, Alexandra M; Guy, Thomas V; Buckley, Adrian; Bolton, Holly A; Zhu, Erhua; Holst, Jeff; Fazekas de St. Groth, Barbara

    2016-07-01

    The importance of CD4 T cells in tumour immunity has been increasingly recognised, with recent reports describing robust CD4 T cell-dependent tumour control in mice whose immune-regulatory mechanisms have been disturbed by irradiation, chemotherapy, immunomodulatory therapy and/or constitutive immunodeficiency. Tumour control in such models has been attributed in large part to direct Major Histocompatibility Complex (MHC) class II-dependent CD4 T cell killing of tumour cells. To test whether CD4 T cells can eradicate tumours without directly killing tumour cells, we developed an animal model in which tumour-derived antigen could be presented to T-cell receptor (TCR)-transgenic CD4 T cells by host but not tumour MHC class II molecules. In I-E(+) mice bearing I-E(null) tumours, naive I-E-restricted CD4 T cells proliferated locally in tumour-draining lymph nodes after recognising tumour-derived antigen on migratory dendritic cells. In lymphopaenic but not immunosufficient hosts, CD4 T cells differentiated into polarised T helper type 1 (Th1) cells expressing interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin (IL)-2 but little IL-17, and cleared established tumours. Tumour clearance was enhanced by higher TCR affinity for tumour antigen-MHC class II and was critically dependent on IFNγ, as demonstrated by early tumour escape in animals treated with an IFNγ blocking antibody. Thus, CD4 T cells and IFNγ can control tumour growth without direct T-cell killing of tumour cells, and without requiring additional adaptive immune cells such as CD8 T cells and B cells. Our results support a role for effective CD4 T cell-dependent tumour immunity against MHC class II-negative tumours. PMID:26837456

  7. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    PubMed

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer. PMID:27208904

  8. IL-8/IL-8 receptor expression in psoriasis and the response to systemic tacrolimus (FK506) therapy.

    PubMed Central

    Lemster, B H; Carroll, P B; Rilo, H R; Johnson, N; Nikaein, A; Thomson, A W

    1995-01-01

    Recently, the keratinocyte IL-8/IL-8 receptor (IL-8R) pathway has been implicated in the pathogenesis of psoriasis, and there is evidence that the potent macrolide immune suppressant tacrolimus (formerly FK506) can inhibit this pathway in vitro. In this study, determination of the expression of cytokine mRNAs in lesional skin of patients with active disease by reverse transcriptase polymerase chain reaction revealed transcripts for IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8, IL-8R, IL-10, interferon-gamma (IFN-gamma), IL-2R and transforming growth factor-beta (TGF-beta), but not IL-2 or IL-4. IL-8 was the only cytokine expressed in affected skin of all patients but not in clinically normal skin of healthy subjects. In seven CD4+ T cell clones propagated from the lesional skin of an untreated psoriasis patient, IL-8 was expressed by the skin-derived T lymphocytes and not by feeder cells (irradiated autologous blood lymphocytes); IL-1 beta, IL-2, IL-6 and IL-10 were also expressed by some or all of the T cell clones. IL-8 mRNA was not detected in the skin of any patient after the start of systemic tacrolimus therapy; IL-1 beta, IL-6 and IFN-gamma transcripts were also reduced. By 12 weeks, the mean psoriasis area and severity index (PASI) had decreased from 18.8 to 3.8, a reduction of 80%. In the same post-treatment biopsies, however, message for IL-8R persisted. Estimation of circulating IL-8 levels by enzyme immunoassay showed that all patients with detectable IL-8 before treatment had decreased levels in response to treatment with tacrolimus; reductions in PASI scores were accompanied by decreases in IL-8 levels, that varied both in rate and extent. Partial relapse, which in a minority of patients followed the initial period of remission, and was precipitated by drug dose reduction, was accompanied by an increase in circulating IL-8. These findings add credence to the view that the IL-8/IL-8R autocrine/paracrine pathway may be important in the

  9. Tumour-like inflammatory abdominal conditions in children.

    PubMed

    Latawiec-Mazurkiewicz, I; Juszkiewicz, P; Pacanowski, J; Kwas, A; Rybkiewicz, M; Rudnicki, J; Walecka, A; Musiał, S

    2005-02-01

    The presence of a tumour, poor general condition, features of anaemia, increased erythrocyte sedimentation rates and imaging suggesting malignancy were the common features in 4 different tumour-like abdominal conditions that are extremely rare in childhood. These conditions included: extensive retroperitoneal tumour with rib involvement that turned out to be an inflammatory lesion caused by Actinomyces in a 12-year-old girl; multi-loculated tumour of the mesentery/ovary caused by mesenteric lymphadenopathy in the course of a Salmonella enteritidis infection in a 2.5-year-old girl; tumour of the VII - VIII hepatic segments that turned out to be the focus of granuloma in the course of lambliasis in a 5.5-year-old boy with a history of purulent neck lymphadenopathy and a final suspicion of immunocompromise; and a multi-loculated tumour of the small pelvis and inguinal area that turned out to be an abscess of the iliopsoas muscle in a 16-year-old boy. Apart from the imaging, the lesions required cytological examination of the material harvested by fine-needle biopsies (liver tumour) or histopathological investigations (retroperitoneal tumour, mesenteric/ovarian tumour, liver tumour and--on second surgery--the pelvic tumour) and/or bacteriological examination (all cases), serological examination (liver tumour and mesenteric/ovarian tumour), protozoal investigation (liver tumour), and measurement of AFP levels (mesenteric/ovarian tumour). Surgical treatment (retroperitoneal tumour, mesenteric/ovarian tumour and tumour of the small pelvis) and guided antibiotic therapy (all cases including 15 weeks of antibiotics in the first case) allowed complete recovery in 3 patients (actinomycosis, mesenteric lymphadenopathy, abscess of the iliopsoas muscle). Antibiotic and antiprotozoal therapy cured the granulomatous hepatitis; however this patient tended to develop severe right-sided pleural/pulmonary changes (the child was referred for further diagnosis with suspicion of

  10. An Ectopic ACTH Secreting Metastatic Parotid Tumour.

    PubMed

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

    2016-01-01

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

  11. Tumour scanning with indium-111 dihaematoporphyrin ether.

    PubMed Central

    Quastel, M. R.; Richter, A. M.; Levy, J. G.

    1990-01-01

    Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection. Images Figure 1 PMID:2147858

  12. An Ectopic ACTH Secreting Metastatic Parotid Tumour

    PubMed Central

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

    2016-01-01

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

  13. Tumour suppressor genes in chemotherapeutic drug response

    PubMed Central

    Lai, Dulcie; Visser-Grieve, Stacy; Yang, Xiaolong

    2012-01-01

    Since cancer is one of the leading causes of death worldwide, there is an urgent need to find better treatments. Currently, the use of chemotherapeutics remains the predominant option for cancer therapy. However, one of the major obstacles for successful cancer therapy using these chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. Therefore identification of genes involved in chemotherapeutic response is critical for predicting tumour response and treating drug-resistant cancer patients. A group of genes commonly lost or inactivated are tumour suppressor genes, which can promote the initiation and progression of cancer through regulation of various biological processes such as cell proliferation, cell death and cell migration/invasion. Recently, mounting evidence suggests that these tumour suppressor genes also play a very important role in the response of cancers to a variety of chemotherapeutic drugs. In the present review, we will provide a comprehensive overview on how major tumour suppressor genes [Rb (retinoblastoma), p53 family, cyclin-dependent kinase inhibitors, BRCA1 (breast-cancer susceptibility gene 1), PTEN (phosphatase and tensin homologue deleted on chromosome 10), Hippo pathway, etc.] are involved in chemotherapeutic drug response and discuss their applications in predicting the clinical outcome of chemotherapy for cancer patients. We also propose that tumour suppressor genes are critical chemotherapeutic targets for the successful treatment of drug-resistant cancer patients in future applications. PMID:22762204

  14. Chest wall tumour following iodized talc pleurodesis

    PubMed Central

    Jackson, John W.; Bennett, M. H.

    1973-01-01

    Jackson, J. W., and Bennett, M. H. (1973).Thorax, 28, 788-793. Chest wall tumour following iodized talc pleurodesis. A man of 37 had an iodized talc pleurodesis carried out for recurrent spontaneous pneumothorax. There was no history of industrial exposure to asbestos. Two years later he presented with pain in the right chest and radiographs at that time showed some localized pleural thickening at the site of the thoracoscopy cannulation for introduction of talc. A provisional diagnosis of talc granuloma, chemical abscess or tumour was made and exploratory thoracotomy revealed a tumour involving the chest wall, lung, and pleura which, on histological examination, showed adenocarcinoma of varying degrees of differentiation and in some parts also presenting a more squamoid appearance. Numerous doubly refractile talc particles were intimately associated with the tumour and fibrous tissue. Shortly after excision the patient developed evidence of systemic dissemination of the disease and died four months later. The possibility of this tumour being induced by the talc is discussed. A brief review is made of the various forms of talc used in surgery over the past 40 years and attention is drawn to the significance of the proportion of asbestos mineral which is present in talc as mined in various parts of the world. We do not consider that this is a case of mesothelioma of the pleura. Images PMID:4787992

  15. Targeting the tumour microenvironment in ovarian cancer.

    PubMed

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. PMID:26849037

  16. Giant malignant phyllodes tumour of breast.

    PubMed

    Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah

    2014-01-01

    The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence. PMID:25548696

  17. Clinical and biological significance of aneuploidy in human tumours.

    PubMed Central

    Friedlander, M L; Hedley, D W; Taylor, I W

    1984-01-01

    Aneuploidy is a well recognised feature of human tumours, but the investigation of its biological and clinical significance has been hampered by technological constraints. Quantitative DNA analysis reflects the total chromosomal content of tumour cells and can now be determined rapidly and reliably using flow cytometry; this has resulted in renewed interest in its potential clinical applications. This article reviews the accumulating evidence that tumour ploidy reflects the biological behaviour of a large number of tumour types and that diploid tumours in particular have a relatively good prognosis. The measurement of tumour ploidy is likely to become a valuable adjunct to the clinical and histopathological assessment of cancers. PMID:6381555

  18. Anaesthetic management of left main bronchial glomus tumour

    PubMed Central

    Krishnakumar, Mathangi; Sharma, Rammurti; Pawar, Harshwardhan Singh; Hasnain, Shahbaz

    2016-01-01

    Glomus tumours involving bronchus are rare. Surgical resection is the treatment of choice for this tumour, with excellent prognosis. The nature and location of tumour pose a significant challenge for perioperative anaesthetic management. However, there is a paucity of case reports on anaesthetic risks involved in case of a bronchial glomus tumour. We present a case of glomus tumour involving left main stem bronchus, subjected to bronchial sleeve resection. The various anaesthetic implications of this tumour type and airway management with right double lumen tube are discussed. PMID:27141112

  19. Novel 1,4-diarylpiperidine-4-methylureas as anti-hyperlipidemic agents: dual effectors on acyl-CoA:cholesterol O-acyltransferase and low-density lipoprotein receptor expression.

    PubMed

    Asano, Shigehiro; Ban, Hitoshi; Kino, Kouichi; Ioriya, Katsuhisa; Muraoka, Masami

    2009-02-15

    A family of 1,4-diarylpiperidine-4-methylureas were designed and synthesized as novel dual effectors on ACAT and LDL receptor expression. We examined SAR of the synthesized compounds focusing on substitution at the three aromatic parts of the starting compound 1 and succeeded in identifying essential substituents for inhibition of ACAT and up-regulation of hepatic LDL receptor expression. Especially, we found that compound 12f, which can easily be prepared, has biological properties comparable to those of SMP-797, a promising ACAT inhibitor. In addition, the in vitro effects of 12f on lipid metabolism were substantially superior to those of a known ACAT inhibitor, Avasimibe. PMID:19167888

  20. The perivascular niche regulates breast tumour dormancy.

    PubMed

    Ghajar, Cyrus M; Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R; Evason, Kimberley J; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A; Stainier, Didier Y R; Chen, Emily I; Lyden, David; Bissell, Mina J

    2013-07-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  1. Viscoelastic properties of human bladder tumours.

    PubMed

    Barnes, S C; Lawless, B M; Shepherd, D E T; Espino, D M; Bicknell, G R; Bryan, R T

    2016-08-01

    The urinary bladder is an organ which facilitates the storage and release of urine. The bladder can develop tumours and bladder cancer is a common malignancy throughout the world. There is a consensus that there are differences in the mechanical properties of normal and malignant tissues. However, the viscoelastic properties of human bladder tumours at the macro-scale have not been previously studied. This study investigated the viscoelastic properties of ten bladder tumours, which were tested using dynamic mechanical analysis at frequencies up to 30Hz. The storage modulus ranged between 0.052MPa and 0.085MPa while the loss modulus ranged between 0.019MPa and 0.043MPa. Both storage and loss moduli showed frequency dependent behaviour and the storage modulus was higher than the loss modulus for every frequency tested. Viscoelastic properties may be useful for the development of surgical trainers, surgical devices, computational models and diagnostic equipment. PMID:27082128

  2. Unusual presentation of a scrotal tumour

    PubMed Central

    Sarkar, Debashis; Parr, Nijel J

    2014-01-01

    A 59-year-old man had a wide excision of the right-sided scrotal cancer in the neck of the scrotum. On dissection it became apparent that the tumour had developed a blood supply from the right spermatic cord. Histology revealed G2T2 squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite groin reported chronic folliculitis. He underwent an ultrasound scanning of the groin and fine-needle aspiration, which did not show any suspicious features. Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3 months to confirm that the spread of the tumour does not follow the pattern of a testicular tumour. PMID:24879734

  3. Post-treatment imaging of liver tumours

    PubMed Central

    Ba-Ssalamah, Ahmed; Kurtaran, Amir; Schindl, Martin; Gruenberger, Thomas

    2007-01-01

    Abstract In the past few years, great improvements have been made to achieve local tumour control of primary liver malignancies and liver metastases. For hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) and tumour ablation techniques, including percutaneous ethanol injection (PEI), radiofrequency ablation (RF), and laser-induced interstitial thermotherapy (LITT) have been developed. For colorectal liver metastases, surgery is still the standard technique in localised disease, although percutaneous RF ablation has gained considerable acceptance. In patients with widespread disease, chemotherapy with new drugs offers improved survival. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice to evaluate treatment response. The present review demonstrates imaging findings of complete and incomplete tumour control after intervention as well as the imaging spectrum of complications. Imaging guidelines according to the World Health Organization and Response Evaluation Criteria In Solid Tumors (RECIST) for assessment of chemotherapy response are presented. PMID:17921098

  4. Tumour Angiogenesis and Angiogenic Inhibitors: A Review

    PubMed Central

    Yadav, Lalita; Puri, Naveen; Satpute, Pranali; Sharma, Vandana

    2015-01-01

    Angiogenesis is a complex process depending on the coordination of many regulators and there by activating angiogenic switch. Recent advances in understanding of angiogenic mechanism have lead to the development of several anti-angiogenic and anti-metastatic agents that use the strategy of regulation of angiogenic switch. Antiangiogenic therapy is a form of treatment not cure for cancer and represents a highly effective strategy for destroying tumour because vascular supply is the fundamental requirement for growth of tumour. Because of the quiescent nature of normal adult vasculature, angiogenic inhibitors are expected to confer a degree of specificity when compared to nonspecific modalities of chemo and radiotherapy, so it has the advantage of less toxicities, does not induce drug resistance and deliver a relatively non toxic, long term treatment of tumour. PMID:26266204

  5. Differential cerebellar GABAA receptor expression in mice with mutations in CaV2.1 (P/Q-type) calcium channels.

    PubMed

    Kaja, S; Payne, A J; Nielsen, E Ø; Thompson, C L; van den Maagdenberg, A M J M; Koulen, P; Snutch, T P

    2015-09-24

    Ataxia is the predominant clinical manifestation of cerebellar dysfunction. Mutations in the human CACNA1A gene, encoding the pore-forming α1 subunit of CaV2.1 (P/Q-type) calcium channels, underlie several neurological disorders, including Episodic Ataxia type 2 and Familial Hemiplegic Migraine type 1 (FHM1). Several mouse mutants exist that harbor mutations in the orthologous Cacna1a gene. The spontaneous Cacna1a mutants Rolling Nagoya (tg(rol)), Tottering (tg) and Leaner (tg(ln)) mice exhibit behavioral motor phenotypes, including ataxia. Transgenic knock-in (KI) mouse strains with the human FHM1 R192Q and S218L missense mutations have been generated. R192Q KI mice are non-ataxic, whereas S218L KI mice display a complex behavioral phenotype that includes cerebellar ataxia. Given the dependence of γ-aminobutyric acid type A (GABAA) receptor subunit functioning on localized calcium currents, and the functional link between GABAergic inhibition and ataxia, we hypothesized that cerebellar GABAA receptor expression is differentially affected in Cacna1a mutants and contributes to the ataxic phenotype. Herein we quantified functional GABAA receptors and pharmacologically dissociated cerebellar GABAA receptors in several Cacna1a mutants. We did not identify differences in the expression of GABAA receptor subunits or in the number of functional GABAA receptors in the non-ataxic R192Q KI strain. In contrast, tg(rol) mice had a ∼15% decrease in the number of functional GABAA receptors, whereas S218L KI mice showed a ∼29% increase. Our data suggest that differential changes in cerebellar GABAA receptor expression profile may contribute to the neurological phenotype of cerebellar ataxia and that targeting GABAA receptors might represent a feasible complementary strategy to treat cerebellar ataxia. PMID:26208839

  6. Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.

    PubMed

    Vassoler, Fair M; Wright, Siobhan J; Byrnes, Elizabeth M

    2016-04-01

    Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA. PMID:26700246

  7. Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl d-aspartate receptor expression

    PubMed Central

    Reichel, Carmela M.; Gilstrap, Meghin G.; Ramsey, Lauren A.; See, Ronald E.

    2013-01-01

    Background Chronic methamphetamine (meth) abuse in humans can lead to various cognitive deficits, including memory loss. We previously showed that chronic meth self-administration impairs memory for objects relative to their location and surrounding objects. Here, we demonstrate that the cognitive enhancer, modafinil, reversed this cognitive impairment independent of glutamate N-methyl d-aspartate (GluN) receptor expression. Methods Male, Long-Evans rats underwent a noncontingent (Experiment 1) or contingent (Experiment 2) meth regimen. After one week of abstinence, rats were tested for object-in-place recognition memory. Half the rats received either vehicle or modafinil (100 mg/kg) immediately after object familiarization. Rats (Experiment 2) were sacrificed immediately after the test and brain areas that comprise the key circuitry for object in place performance were manually dissected. Subsequently, glutamate receptor expression was measured from a crude membrane fraction using western blot procedures. Results Saline-treated rats spent more time interacting with the objects in changed locations, while meth-treated rats distributed their time equally among all objects. Meth-treated rats that received modafinil showed a reversal in the deficit, whereby they spent more time exploring the objects in the new locations. GluN2B receptor subtype was decreased in the perirhinal cortex, yet remained unaffected in the prefrontal cortex and hippocampus of meth rats. This meth-induced down regulation occurred whether or not meth experienced rats received vehicle or modafinil. Conclusions These data support the use of modafinil for memory impairment in meth addiction. Further studies are needed to elucidate the neural mechanisms of modafinil reversal of cognitive impairments. PMID:24120858

  8. High frequency of tumours in Mulibrey nanism.

    PubMed

    Karlberg, Niklas; Karlberg, Susann; Karikoski, Riitta; Mikkola, Sakari; Lipsanen-Nyman, Marita; Jalanko, Hannu

    2009-06-01

    Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. In this work, the frequency and pathology of malignant and benign tumours were analysed in a national cohort of 89 Finnish MUL patients aged 0.7-76 years. The subjects had a clinical and radiological evaluation, and histological and immunohistocemical analyses on specimens obtained from biopsy, surgery or autopsy, were performed. The results show that the MUL patients have disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours detectable in several internal organs. A total of 210 tumorous lesions were detected in 66/89 patients (74%). Fifteen malignancies occurred in 13 patients (15%), seven of them in the kidney (five Wilms' tumours), three in the thyroid gland, two gynaecological cancers, one gastrointestinal carcinoid tumour, one neuropituitary Langerhans cell histiocytosis and one case of acute lymphoblastic leukaemia (ALL). Tumours detected by radiology in the liver and other organs mainly comprised strongly dilated blood vessels (peliosis), vascularized cysts and nodular lesions. The lesions showed strong expression of the endothelial cell markers CD34 and CD31 as well as the myocyte marker alpha-smooth muscle actin (alpha-SMA). Our findings show that MUL is associated with frequent malignant tumours and benign adenomatous and vascular lesions, as well as disturbed organ development. PMID:19334051

  9. Anti-tumour strategies aiming to target tumour-associated macrophages

    PubMed Central

    Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

    2013-01-01

    Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

  10. Sertoliform cystadenoma: a rare benign tumour of the rete testis

    PubMed Central

    2013-01-01

    Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335 PMID:23406299

  11. Sertoli cell tumour in an Amur tiger.

    PubMed

    Scudamore, C L; Meredith, A L

    2001-01-01

    The histological and immunohistochemical characteristics of a malignant Sertoli cell tumour in a 17-year-old Amur tiger (Panthera tigris altaica) are described. Histological examination of the primary lesion in the right testis and metastatic lesions throughout the internal organs showed a variable cellular pattern with an admixture of tubular structures divided by fine stroma filled with fusiform to stellate cells, and sheets of polygonal cells with abundant vacuolated cytoplasm. Immunohistochemical techniques demonstrated strong positive staining for neuron-specific enolase and variable positive staining for vimentin in neoplastic cells, supporting a diagnosis of a tumour of Sertoli cell origin. PMID:11428192

  12. Metastatic colonization by circulating tumour cells.

    PubMed

    Massagué, Joan; Obenauf, Anna C

    2016-01-21

    Metastasis is the main cause of death in people with cancer. To colonize distant organs, circulating tumour cells must overcome many obstacles through mechanisms that we are only now starting to understand. These include infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds and eventually breaking out to replace the host tissue. They make metastasis a highly inefficient process. However, once metastases have been established, current treatments frequently fail to provide durable responses. An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer. PMID:26791720

  13. Thoracic Wall Reconstruction in Advanced Breast Tumours

    PubMed Central

    Daigeler, A.; Harati, K.; Goertz, O.; Hirsch, T.; Behr, B.; Lehnhardt, M.; Kolbenschlag, J.

    2014-01-01

    In advanced mammary tumours, extensive resections, sometimes involving sections of the thoracic wall, are often necessary. Plastic surgery reconstruction procedures offer sufficient opportunities to cover even large thoracic wall defects. Pedicled flaps from the torso but also free flap-plasties enable, through secure defect closure, the removal of large, ulcerated, painful or bleeding tumours with moderate donor site morbidity. The impact of thoracic wall resection on the respiratory mechanism can be easily compensated for and patientsʼ quality of life in the palliative stage of disease can often be improved. PMID:24976636

  14. Extracutaneous glomus tumour of the trachea

    PubMed Central

    Łochowski, Mariusz Piotr; Jesionek-Kupnicka, Dorota; Kozak, Józef

    2015-01-01

    A 38-year-old man presenting expiratory stridor and high-grade dyspnoea was admitted to hospital in Lodz in February 2013. Chest radiographs and computed tomography scans showed a solid lesion in the upper part of the trachea occluding 85% of the airway lumen. A segmental resection of the trachea with a subsequent end-to-end anastomosis was performed. Histopathology showed an extracutaneous glomus tumour. There were no postoperative complications. Tracheal resection is the primary curative method in cases of this rare tumour. PMID:26702289

  15. A Large Extragnathic Keratocystic Odontogenic Tumour

    PubMed Central

    Bavle, Radhika M.; Muniswamappa, Sudhakara; Narasimhamurthy, Srinath

    2015-01-01

    Odontogenic keratocysts (OKCs) are developmental cysts which occur typically in the jawbones. They present more commonly in the posterior mandible of young adults than the maxilla. OKCs have been reclassified under odontogenic tumours in 2005 by the WHO and have since been termed as keratocystic odontogenic tumours (KCOTs). Here we report a case of a recurrent buccal lesion in a 62-year-old man which was provisionally diagnosed as a space infection (buccal abscess) but surprisingly turned out to be a soft tissue KCOT in an unusual location on histopathologic examination. PMID:26770859

  16. SINGLE-WALLED CARBON NANOTUBE–MEDIATED SMALL INTERFERING RNA DELIVERY AND SILENCING GASTRIN-RELEASING PEPTIDE RECEPTOR IN HUMAN NEUROBLASTOMA CELLS

    PubMed Central

    Qiao, Jingbo; Hong, Tu; Guo, Honglian; Xu, Ya-Qiong; Chung, Dai H.

    2015-01-01

    Small interfering RNA (siRNA) has the potential to influence expression with a high degree of target gene specificity. However, the clinical application of siRNA therapeutics has proven to be less promising as evidenced by poor intracellular uptake, instability in vivo, and non-specific immune stimulations. Recently, we have demonstrated that single-walled carbon nanotube (SWNT)-mediated siRNA delivery can enhance the efficiency of siRNA-mediated gastrin-releasing peptide receptor (GRP-R) gene silencing by stabilizing siRNA while selectively targeting tumor tissues. Based on our recent findings, we introduce a novel technique to silence specific gene(s) in human neuroblastoma through SWNT-mediated siRNA delivery in vitro and in vivo. PMID:23749575

  17. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  18. Systematic pan-cancer analysis of tumour purity

    PubMed Central

    Aran, Dvir; Sirota, Marina; Butte, Atul J.

    2015-01-01

    The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses. PMID:26634437

  19. Intraoperative intravital microscopy permits the study of human tumour vessels.

    PubMed

    Fisher, Daniel T; Muhitch, Jason B; Kim, Minhyung; Doyen, Kurt C; Bogner, Paul N; Evans, Sharon S; Skitzki, Joseph J

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  20. Brain tumour cells interconnect to a functional and resistant network.

    PubMed

    Osswald, Matthias; Jung, Erik; Sahm, Felix; Solecki, Gergely; Venkataramani, Varun; Blaes, Jonas; Weil, Sophie; Horstmann, Heinz; Wiestler, Benedikt; Syed, Mustafa; Huang, Lulu; Ratliff, Miriam; Karimian Jazi, Kianush; Kurz, Felix T; Schmenger, Torsten; Lemke, Dieter; Gömmel, Miriam; Pauli, Martin; Liao, Yunxiang; Häring, Peter; Pusch, Stefan; Herl, Verena; Steinhäuser, Christian; Krunic, Damir; Jarahian, Mostafa; Miletic, Hrvoje; Berghoff, Anna S; Griesbeck, Oliver; Kalamakis, Georgios; Garaschuk, Olga; Preusser, Matthias; Weiss, Samuel; Liu, Haikun; Heiland, Sabine; Platten, Michael; Huber, Peter E; Kuner, Thomas; von Deimling, Andreas; Wick, Wolfgang; Winkler, Frank

    2015-12-01

    Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease. PMID:26536111

  1. Pedunculated islet-cell tumour of the duodenum.

    PubMed

    Britt, R P

    1966-05-01

    An unusual islet-cell tumour found at necropsy in a patient who had died from a myocardial infarction is described. Of particular interest were the pedunculated nature and large size of the tumour. The clinical features of the case are considered. Four islet-cell tumours in the duodenum have previously been reported and it seems probable that such tumours arise in heterotopic pancreas. PMID:4287114

  2. Büschke-Lowenstein tumour in pregnancy.

    PubMed

    Garozzo, G; Nuciforo, G; Rocchi, C M; Bonanno, N M; Sampugnaro, E G; Piccione, S; Di Stefano, A; Acquaviva, G; Barberi, A L; Panella, M

    2003-11-10

    During pregnancy a localised human papillomavirus (HPV) lesion may, in rare cases, develop into a Büschke-Lowenstein tumour. The choice of treatment is crucial as standard systemic treatment is teratogenic. We performed laser CO2 microsurgery because it has a low incidence of complications. PMID:14557019

  3. Vagal Schwannoma: A Rare Parapharyngeal Tumour.

    PubMed

    Kamath, Panduranga M; Dosemane, Deviprasad; Sreedharan, Suja S; Majeed, Nazeem A; Shenoy, Vijendra S

    2016-04-01

    Among the parapharyngeal tumours, salivary gland tumours are the commonest, followed by schwannomas, which are slow growing benign tumours. Half of the parapharyngeal schwannomas originate from the vagus. Complete surgical excision is the treatment of choice. We hereby present two cases of parapharyngeal schwannomas, one which had presented as an intraoral mass and the other as a swelling in the neck. The first case, a 57-year-old female patient complained of a slowly increasing swelling in the left side of the throat since 3 months, associated with pain and dysphagia. In the Contrast Enhanced CT scan of the neck, a well-defined cystic lesion with central enhancing solid components (4cm X 4.5cm X 3cm) was seen in the left parapharyngeal region. The second case, a 39-year-old male patient complained of a painless, gradually increasing swelling below the lobule of the right ear since one month. Examination revealed a solitary, nontender, firm and mobile swelling of 2cm X 2cm below the lobule of the right ear. In Contrast Enhanced CT scan of the neck, an enhancing lesion was seen involving the right parapharyngeal space, post-styloid compartment. Both the patients underwent trans-cervical surgical excision. Vagal nerve schwannoma is rare. The majority of the cases present with a slow growing neck swelling without neurological deficit. Complete surgical excision of the tumour is important to prevent recurrence. PMID:27190844

  4. Karyotypic abnormalities in tumours of the pancreas.

    PubMed Central

    Bardi, G.; Johansson, B.; Pandis, N.; Mandahl, N.; Bak-Jensen, E.; Andrén-Sandberg, A.; Mitelman, F.; Heim, S.

    1993-01-01

    Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours. Images Figure 1 PMID:8494707

  5. Analysis of nanoparticle delivery to tumours

    NASA Astrophysics Data System (ADS)

    Wilhelm, Stefan; Tavares, Anthony J.; Dai, Qin; Ohta, Seiichi; Audet, Julie; Dvorak, Harold F.; Chan, Warren C. W.

    2016-05-01

    Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.

  6. Molecular mechanisms for tumour resistance to chemotherapy.

    PubMed

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it. PMID:27097837

  7. Canine oral mucosal mast cell tumours.

    PubMed

    Elliott, J W; Cripps, P; Blackwood, L; Berlato, D; Murphy, S; Grant, I A

    2016-03-01

    Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present. PMID:24215587

  8. Solitary fibrous tumour of the cheek: An unusual presentation of a rare soft tissue tumour

    PubMed Central

    Jones, JL; Jones, AV; Drage, NA; Bhatia, S; Hourihan, MD

    2014-01-01

    This case report discusses the unusual presentation and ultrasound features of a solitary fibrous tumour of the face. Solitary fibrous tumour is an uncommon form of soft tissue tumour which, although seen predominantly within the lung pleura, can occur throughout the body in sites such as the peritoneum, mediastinum and head and neck. Ultrasound is an excellent imaging modality in the assessment of soft tissue masses in the head and neck. The ultrasound features demonstrated by this example of solitary fibrous tumour are reviewed. This report also highlights that ultrasound alone is ultimately limited in reaching a definitive diagnosis. The roles of other investigations such as ultrasound-guided biopsy and cross-sectional imaging are discussed.

  9. Neuropsychological Differences between Survivors of Supratentorial and Infratentorial Brain Tumours

    ERIC Educational Resources Information Center

    Patel, S. K.; Mullins, W. A.; O'Neil, S. H.; Wilson, K.

    2011-01-01

    Background: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined…

  10. Anti - tumour activity of an ayurvedic oil preparation.

    PubMed

    Panikar, K R; Bhanumathy, P; Raghunath, P N

    1986-10-01

    An ayurvedic oil preparation containing flowers of ixora coccinea and cortus sativum was subjected to an animal experimentation to find out how far it is efficient in preventing the development of Dalton's lymphoma as solid tumour. The oil was applied after injecting the cells and we found it could retard the development of tumour and arrest further development of already formed tumour. PMID:22557556

  11. ANTI – TUMOUR ACTIVITY OF AN AYURVEDIC OIL PREPARATION

    PubMed Central

    Panikar, K. R.; Bhanumathy, P.; Raghunath, P. N.

    1986-01-01

    An ayurvedic oil preparation containing flowers of ixora coccinea and cortus sativum was subjected to an animal experimentation to find out how far it is efficient in preventing the development of Dalton's lymphoma as solid tumour. The oil was applied after injecting the cells and we found it could retard the development of tumour and arrest further development of already formed tumour. PMID:22557556

  12. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

    PubMed Central

    Habets, Thomas H. P. M.; Oth, Tammy; Houben, Ans W.; Huijskens, Mirelle J. A. J.; Senden-Gijsbers, Birgit L. M. G.; Schnijderberg, Melanie C. A.; Brans, Boudewijn; Dubois, Ludwig J.; Lambin, Philippe; De Saint-Hubert, Marijke; Germeraad, Wilfred T. V.; Tilanus, Marcel G. J.; Mottaghy, Felix M.

    2016-01-01

    Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects. PMID:27427766

  13. Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness

    PubMed Central

    Avgustinova, Alexandra; Iravani, Marjan; Robertson, David; Fearns, Antony; Gao, Qiong; Klingbeil, Pamela; Hanby, Andrew M.; Speirs, Valerie; Sahai, Erik; Calvo, Fernando; Isacke, Clare M.

    2016-01-01

    Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome. PMID:26777421

  14. Treatment of spontaneous tumours by temporary local ligation

    PubMed Central

    Allen, Frederick M.; Kaplan, Martin M.; Meranze, David R.; Gradess, Morton

    1960-01-01

    Previous work in some human cases and in laboratory animals has indicated that temporary local ligation of spontaneous tumours has a selective destructive effect on these tumours, with only temporary inflammation resulting in normal tissues. In the experiments described in this paper, 49 spontaneous accessible tumours in dogs were treated by this method, with periods of ligation of from 4 to 11 hours. Success, as measured by selective necrosis of tumour tissue as compared with normal tissue, was achieved in 29 out of 41 benign tumours, including lipomas, angiomas, adenomas and mixed mammary tumours. Treatment failures were encountered in two cases each of papillomas and fibromas, six mixed mammary tumours and two testicular tumours. Total necrosis of tumour cells occurred in all eight malignant tumours encountered in this series. The outstanding feature was the specific destruction of tumour tissue by a bodily process without participation of any outside agent. Emphasis was placed on an adequate inflammatory response following temporary anoxia, although a precise definition of this inflammation could not be offered. Post-ligation bacterial multiplication, which may be expected to occur in necrotic tumour tissue, is considered to be a secondary effect rather than a possible primary cause of regression and disappearance of the tumour. If ligation treatment can be shown to be successful for a particular type of tumour, it may be possible to apply it to human patients for the treatment of areas not amenable to surgery. The results reported here warrant new experimental approaches to the study of neoplasms at the cellular level to define more precisely the anoxic and inflammatory processes involved in the selective lethal effect on tumour tissues; and the authors suggest that trials should be undertaken of combinations of chemotherapy or irradiation with ligation to reduce ligation time and extend the possible benefits. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7

  15. Ovarian Steroid Cell Tumour: Correlation of Histopathology with Clinicopathologic Features

    PubMed Central

    Mehdi, Ghazala; Ansari, Hena A.; Sherwani, Rana K.; Rahman, Khaliqur; Akhtar, Nishat

    2011-01-01

    Ovarian steroid cell tumours (not otherwise specified) are rare neoplasms of the ovary and are classified under lipid cell tumours. Their diagnosis can be considered as one of exclusion. Histopathologically, the tumour should carefully be evaluated for microscopic features of malignancy, but it is essential for the clinician and the pathologist to remember that in these tumours, pathologically benign histomorphology does not exclude the possibility of clinically malignant behaviour. Our case study focuses on the comparative findings in a postmenopausal female diagnosed with an ovarian steroid tumour (not otherwise specified). A careful correlation between clinical and surgical evaluation and microscopic analysis is necessary, as is a regular followup. PMID:21436872

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  17. Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity.

    PubMed

    Frey, Benjamin; Derer, Anja; Scheithauer, Heike; Wunderlich, Roland; Fietkau, Rainer; Gaipl, Udo S

    2016-01-01

    Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence-associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies. PMID:27558821

  18. Insulin-like growth factor I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15.

    PubMed

    Siebler, T; Lopaczynski, W; Terry, C L; Casella, S J; Munson, P; De Leon, D D; Phang, L; Blakemore, K J; McEvoy, R C; Kelley, R I

    1995-12-01

    Most patients with deletion of the distal long arm of chromosome 15 have intrauterine growth retardation and postnatal growth deficiency in addition to developmental abnormalities. It has been proposed that the absence of one copy of the insulin-like growth factor I (IGF-I) receptor gene may play a role in the growth deficiency seen in this syndrome. To address this question we examined IGF-I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15 (15q26.1-->qter). Quantitative Southern blot analysis of the IGF-I receptor gene was performed on HindIII digests of fibroblast DNA. Radioactivity in the 1.7-kilobase receptor fragment in the two patients was 55% and 51% of the values in controls, consistent with the absence of one copy of the IGF-I receptor gene. IGF-I receptor messenger ribonucleic acid levels were quantitated by a solution hybridization/nuclease protection assay. Receptor messenger ribonucleic acid levels in the two patients were 45% and 52% of the values in controls. Northern blotting demonstrated normal size IGF-I receptor transcripts and affinity crosslinking of [125I]IGF-I to Triton X-100-solubilized fibroblasts demonstrated a normal size receptor in the patients. Analysis of placental membranes prepared from one patient revealed no difference in [125I]IGF-I binding. In the patients' fibroblasts, however, binding of [125I]long [R3]-IGF-I to the IGF-I receptor was significantly reduced, as assessed by the amount of radioactivity competed by the monoclonal antibody alpha IR-3 or insulin and Scatchard analysis of binding data. To assess IGF-I receptor function, stimulation of [alpha-1-14C]-methylaminoisobutyric acid transport and stimulation of [methyl-3H]thymidine incorporation into DNA by a full range of IGF-I concentrations was examined in patient and control fibroblasts. There was a significant decrease in the maximal response to IGF-I in both assays for one of the two patients when

  19. Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers.

    PubMed

    Goldsmith, S K; Joyce, J N

    1994-06-01

    A detailed study comparing the distribution of D2 receptors and tyrosine hydroxylase-immunoreactive fibers in the hippocampus and parahippocampal cortices of the rat, cat, and human was conducted. The distribution of [125I]epidepride binding to D2 receptors along the transverse and longitudinal axes of the hippocampus and parahippocampus differed among the species. In rat hippocampus, the number of sites was highest in septal portions of lacunosum-moleculare of CA1 and stratum moleculare of the subiculum. Virtually no binding to D2 receptors existed in the temporal hippocampus. For the cat hippocampus, the highest binding existed in the inner one-third of the molecular layer of the dentate gyrus (DG). There were also significant numbers of D2 receptors in strata radiatum and oriens of the CA subfields, with almost undetectable levels in lacunosum moleculare and subiculum. The number of sites was higher in the septal than temporal hippocampus. In the human hippocampus, highest binding was observed in the molecular layer of DG and the subiculum, with lower levels in strata oriens and lacunosum-moleculare of CA3, and very low binding in CA1. The histochemical demonstration of the pattern of mossy fibers revealed an organization complementary to that of D2 receptors in cat and human. In none of the species was there significant expression of D2 receptors in the entorhinal cortex, except in the caudal extreme of this region in the rat. In that region a trilaminar pattern was exhibited that continued into the perirhinal cortex. A trilaminar pattern of D2 receptor expression was observed in the perirhinal cortex of all species, with the highest values in the external and deep laminae and low expression in the middle laminae. The organization of dopamine fibers was assessed by comparing the distribution of tyrosine hydroxylase-positive and dopamine beta-hydroxylase-immunoreactive fibers in these same regions. It revealed consistent mismatches between the pattern of D2

  20. Type I Interferon Elevates Co-Regulatory Receptor Expression on CMV- and EBV-Specific CD8 T Cells in Chronic Hepatitis C

    PubMed Central

    Owusu Sekyere, Solomon; Suneetha, Pothakamuri Venkata; Hardtke, Svenja; Falk, Christine Susanne; Hengst, Julia; Manns, Michael Peter; Cornberg, Markus; Wedemeyer, Heiner; Schlaphoff, Verena

    2015-01-01

    Hepatitis C virus (HCV) readily sets up persistence in a large fraction of infected hosts. Mounting epidemiological and immunological evidence suggest that HCV’s persistence could influence immune responses toward unrelated pathogens and vaccines. Nonetheless, the fundamental contribution of the inflammatory milieu during persistent HCV infection in impacting immune cells specific for common pathogens such as CMV and EBV has not been fully studied. As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8+ T cell function, we assessed their expression on CMV/EBV-specific CD8+ T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. Total and CMV/EBV-specific CD8+ T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8+ T cells in CHC patients. Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. Importantly, IFNα-2a further caused upregulation of these markers upon in vitro peptide stimulation. Finally, we could prospectively study patients receiving novel IFN-free antiviral therapy. Here, we observed that treatment-induced clearance of HCV resulted in a partial reversion of the phenotype of CMV/EBV-specific CD8+ T cells in patients with CHC. These data reveal an alteration of the plasma concentrations of IFNα-2a together with other inflammatory mediators during CHC, which appeared to pervasively influence co-regulatory receptor expression on CMV/EBV-specific CD8+ T cells. PMID:26113847

  1. Computed tomography predictors of hepatocellular carcinoma tumour necrosis after chemoembolization

    PubMed Central

    Bryant, Mary K; Dorn, David P; Zarzour, Jessica; Smith, J Kevin; Redden, David T; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen H; Eckhoff, Devin E; DuBay, Derek A

    2014-01-01

    Background Radiographical features associated with a favourable response to trans-arterial chemoembolization (TACE) are poorly defined for patients with hepatocellular carcinoma (HCC). Methods From 2008 to 2012, all first TACE interventions for HCC performed at the University of Alabama at Birmingham (UAB) were retrospectively reviewed. Only patients with a pre-TACE and a post-TACE computed tomography (CT) scan were included in the analyses (n = 115). HCC tumour response to TACE was quantified via the the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Univariate and multivariable analyses were constructed. Results The index HCC tumours experienced a > 90% or complete tumour necrosis in 59/115 (51%) of patients after the first TACE intervention. On univariate analysis, smaller tumour size, peripheral tumour location and arterial enhancement were associated with a > 90% or complete tumour necrosis, whereas, only smaller tumour size [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.48, 0.81] and peripheral location (OR 6.91; 95% CI 1.75, 27.29) were significant on multivariable analysis. There was a trend towards improved survival in the patients that experienced a > 90% or complete tumour necrosis (P = 0.08). Conclusions Peripherally located smaller HCC tumours are most likely to experience a > 90% or complete tumour necrosis after TACE. Surprisingly, arterial-phase enhancement and portal venous-phase washout were not significantly predictive of TACE-induced tumour necrosis. The TACE response was not statistically associated with improved survival. PMID:23980917

  2. Incidence and prevalence of salivary gland tumours in Valparaiso, Chile

    PubMed Central

    Araya, Juan; Martinez, René; Niklander, Sven; Marshall, Maureen

    2015-01-01

    Background To determine the incidence and prevalence of salivary gland tumours in the province of Valparaíso, Chile. Material and Methods Retrospective review of salivary gland tumours diagnosed between the years 2000 and 2011 from four local pathology services. Information on demographics and histopathology were retrieved from the medical records. Results The study sample consisted of 279 salivary gland tumours. Prevalence and incidence rates per 100.000 persons were 15.4 and 2.51, respectively. Most of the neoplasms corresponded to benign tumours (70.3%). The most affected gland was the parotid gland. Pleomorphic adenoma was the most common benign tumour (53.8%) and mucoepidermoid carcinoma was the most common malignant tumour (7.2%). Conclusions Salivary gland tumours are uncommon neoplasms that usually arise in the parotid gland. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common benign and malignant tumours reported in this series. Key words:Salivary gland tumours, benign tumours, malignant tumours, salivary glands neoplasms, cancer, neoplasia. PMID:26034925

  3. Enhancement of T cell recruitment and infiltration into tumours

    PubMed Central

    Oelkrug, C; Ramage, J M

    2014-01-01

    Studies have documented that cancer patients with tumours which are highly infiltrated with cytotoxic T lymphocytes show enhanced survival rates. The ultimate goal of cancer immunotherapy is to elicit high-avidity tumour-specific T cells to migrate and kill malignant tumours. Novel antibody therapies such as ipilumimab (a cytotoxic T lymphocyte antigen-4 blocking antibody) show enhanced T cell infiltration into the tumour tissue and increased survival. More conventional therapies such as chemotherapy or anti-angiogenic therapy and recent therapies with oncolytic viruses have been shown to alter the tumour microenvironment and thereby lead to enhanced T cell infiltration. Understanding the mechanisms involved in the migration of high-avidity tumour-specific T cells into tumours will support and provide solutions for the optimization of therapeutic options in cancer immunotherapy. PMID:24828133

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

    PubMed Central

    Das, Anirban; Pratap, Abhishek

    2016-01-01

    Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment. PMID:27034865

  5. Tumours and cancers in Graeco-Roman times.

    PubMed

    Retief, F P; Cilliers, L

    2001-04-01

    In Graeco-Roman times all tumours (Greek: onkoi, abnormal swellings) were considered to be of inflammatory origin, the result of unfavourable humoural fluxes, and caused by an extravascular outpouring of fluid into tissue spaces. The neoplastic nature of tumours is a more recent concept, barely two centuries old. In Hippocratic literature tumours were mainly classified as karkinômata, phumata, and oidêmata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), while oidêmata were soft, painless tumours and even included generalised oedema (dropsy). Although all categories possibly included occasional cancers, the vast majority of what appears to have been malignant tumours were called karkinoi karkinômata (Latin: cancrum/carcinoma). There was, however, no recognition of benign and malignant, primary and secondary tumours, in the modern sense. PMID:11402909

  6. BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas

    PubMed Central

    O’Neill, Hannah L.; Cassidy, Amy P.; Harris, Olivia B.

    2016-01-01

    Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas. PMID:27114889

  7. Effects of nandrolone decanoate on the toxicity and anti-tumour action of CCNU and FU in murine tumours.

    PubMed Central

    Bibby, M. C.; Double, J. A.; Mughal, M. A.

    1981-01-01

    Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND. PMID:7295514

  8. LKB1, the multitasking tumour suppressor kinase

    PubMed Central

    Marignani, P A

    2005-01-01

    Mutations in the lkb1 gene are found in Peutz-Jeghers syndrome (PJS), with loss of heterozygosity or somatic mutations at the lkb1 locus, suggesting the gene product, the serine/threonine kinase LKB1, may function as a tumour suppressor. Patients with PJS are at a greater risk of developing cancers of epithelial tissue origin. It is widely accepted that the presence of hamartomatous polyps in PJS does not in itself lead to the development of malignancy. The signalling mechanisms that lead to these PJS related malignancies are not well understood. However, it is evident from the recent literature that LKB1 is a multitasking kinase, with unlimited potential in orchestrating cell activity. Thus far, LKB1 has been found to play a role in chromatin remodelling, cell cycle arrest, Wnt signalling, cell polarity, and energy metabolism, all of which may require the tumour suppressor function of this kinase and/or its catalytic activity. PMID:15623475

  9. Improved tumour response by laser light treatment

    NASA Astrophysics Data System (ADS)

    Graschew, Georgi; Smith, Janice; Rakowsky, Stefan; Roelofs, Theo A.; Schlag, Peter M.; Stein, Ulrike

    2008-04-01

    Multidrug resistance (MDR) poses a serious barrier to the efficacy of clinical treatment of human cancers with chemotherapeutic drugs. This barrier might be reduced and eventually overcome by the simultaneous application of two or more treatment modalities. This study reports on the synergetic effect of combined application of laser light and cytostatic drugs to induce an improved tumour response in MDR cancer cells. The MDR breast cancer cell line MaTu/ADR, resistant to the drug adriamycin (ADR), was treated with a combination of ADR (125-1000 ng/ml) and laser light (488 nm with a total light dose between 6-18 J/cm2). This combined treatment leads to an additional reduction of the cell vitality by a factor of 2-3 as compared to treatment with ADR alone, suggesting that combined application of laser light and other treatment modalities might constitute a promising strategy for improvements in the tumour response.

  10. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    PubMed

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

    2016-01-01

    In the past decades, the number of neuroendocrine tumours that are detected is increasing. A relative new and promising therapy for patients with metastasised or inoperable disease is peptide receptor radionuclide therapy (PRRT). This therapy involves an infusion of somatostatin analogues linked to radionuclides like Yttrium-90 or Lutetium-177. Objective response rates are reported in 15-35%. Response rates may vary between type of tumour and radionuclide. Besides the objective response rate, overall survival and progression free survival increase significantly. Also, the quality of life improves as well. Serious side-affects are rare. PRRT is usually well tolerated, also in patients with extensive metastasised disease. Recent studies combined PRRT with other types of therapies. Unfortunately no randomised trials comparing these strategies are available. In the future, more research is needed to evaluate the best therapy combinations or sequence of therapies. PMID:26971847

  11. Perivascular epithelioid cell tumour of the bladder

    PubMed Central

    Tarplin, Sarah; Osterberg, E Charles; Robinson, Brian D; Herman, Michael P; Rosoff, James S

    2014-01-01

    A 39-year-old woman presented with a long history of pelvic pain and urinary urgency. Prior workup by her primary care doctor had been negative. The patient's gynaecologist ultimately referred her to a urologist following an ultrasound that revealed a possible bladder mass. MRI of the abdomen and pelvis demonstrated a 4 cm soft tissue lesion arising from the bladder. Cystoscopy showed an atypical mass on the anterior bladder wall, and pathological examination of the TURBT (transurethral resection of the bladder tumour) specimen revealed a perivascular epithelioid cell tumour (PEComa) with involvement of the detrusor muscle. The patient underwent a robotically assisted laparoscopic partial cystectomy. Final pathology confirmed a PEComa with negative margins. The patient had an uncomplicated postoperative course and is doing well following surgery. A surveillance cystoscopy at 6 months showed no evidence of recurrence. This case underscores the variability of clinical presentation of PEComas while proposing an appropriate method of surgical management. PMID:25123573

  12. An unusual tumour of the lung.

    PubMed

    Ayadi, L; Abid, N; Makni, S; Bahri, I; Frikha, I; Sellami-Boudawara, T

    2015-03-01

    We report a case of a 51-year-old woman with a solitary mast cell tumour of the lung, a rare neoplasm with only three previously-reported cases reported in the literature. Unlike previous cases, the tumour in the present case was bulky, measuring 14 cm in diameter and budding into the segmental bronchus. Histologically, it showed proliferation of typical metachromatic mast cells intermingled with undifferentiated cells with a ratio of 3:1. The neoplastic mast cells stained strongly with tryptase, CD117, CD68 and CD45, CD14 and CD33; whereas the undifferentiated cells lacked all these markers and expressed EMA and cytokeratin. Histological examination of bone marrow and laboratory data were unremarkable. To our knowledge, this is the fourth case of solitary extracutaneous mastocytoma of the lung. The differentiating features of this neoplasm and a review of literature are presented. PMID:26591626

  13. Mutational patterns in oncogenes and tumour suppressors.

    PubMed

    Baeissa, Hanadi M; Benstead-Hume, Graeme; Richardson, Christopher J; Pearl, Frances M G

    2016-06-15

    All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved. In this paper we examine the mutation patterns observed in oncogenes and tumour suppressors, and discuss different approaches that have been developed to identify driver mutations within cancers that contribute to the disease progress. We also discuss the MOKCa database where we have developed an automatic pipeline that structurally and functionally annotates all proteins from the human proteome that are mutated in cancer. PMID:27284061

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

    PubMed Central

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

    2003-01-01

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

  15. ABCB1 in children's brain tumours.

    PubMed

    Coyle, Beth; Kessler, Maya; Sabnis, Durgagauri H; Kerr, Ian D

    2015-10-01

    Tumours of the central nervous system are the most common solid tumour, accounting for a quarter of the 1500 cases of childhood cancer diagnosed each year in the U.K. They are the most common cause of cancer-related death in children. Treatment consists of surgery followed by adjuvant chemotherapy and/or radiotherapy. Survival rates have generally increased, but many survivors suffer from radiotherapy-related neurocognitive and endocrine side effects as well as an increased risk of secondary cancer. Adjuvant chemotherapy is normally given in combination to circumvent chemoresistance, but several studies have demonstrated it to be ineffective in the absence of radiotherapy. The identification of children with drug-resistant disease at the outset could allow stratification of those that are potentially curable by chemotherapy alone. Ultimately, however, what is required is a means to overcome this drug resistance and restore the effectiveness of chemotherapy. Medulloblastomas and ependymomas account for over 30% of paediatric brain tumours. Advances in neurosurgery, adjuvant radiotherapy and chemotherapy have led to improvements in 5-year overall survival rates. There remain, however, significant numbers of medulloblastoma patients that have intrinsically drug-resistant tumours and/or present with disseminated disease. Local relapse in ependymoma is also common and has an extremely poor prognosis with only 25% of children surviving first relapse. Each of these is consistent with the acquisition of drug and radiotherapy resistance. Since the majority of chemotherapy drugs currently used to treat these patients are transport substrates for ATP-binding cassette sub-family B member 1 (ABCB1) we will address the hypothesis that ABCB1 expression underlies this drug resistance. PMID:26517917

  16. Malignant testicular tumour incidence and mortality trends

    PubMed Central

    Wojtyła-Buciora, Paulina; Więckowska, Barbara; Krzywinska-Wiewiorowska, Małgorzata; Gromadecka-Sutkiewicz, Małgorzata

    2016-01-01

    Aim of the study In Poland testicular tumours are the most frequent cancer among men aged 20–44 years. Testicular tumour incidence since the 1980s and 1990s has been diversified geographically, with an increased risk of mortality in Wielkopolska Province, which was highlighted at the turn of the 1980s and 1990s. The aim of the study was the comparative analysis of the tendencies in incidence and death rates due to malignant testicular tumours observed among men in Poland and in Wielkopolska Province. Material and methods Data from the National Cancer Registry were used for calculations. The incidence/mortality rates among men due to malignant testicular cancer as well as the tendencies in incidence/death ratio observed in Poland and Wielkopolska were established based on regression equation. The analysis was deepened by adopting the multiple linear regression model. A p-value < 0.05 was arbitrarily adopted as the criterion of statistical significance, and for multiple comparisons it was modified according to the Bonferroni adjustment to a value of p < 0.0028. Calculations were performed with the use of PQStat v1.4.8 package. Results The incidence of malignant testicular neoplasms observed among men in Poland and in Wielkopolska Province indicated a significant rising tendency. The multiple linear regression model confirmed that the year variable is a strong incidence forecast factor only within the territory of Poland. A corresponding analysis of mortality rates among men in Poland and in Wielkopolska Province did not show any statistically significant correlations. Conclusions Late diagnosis of Polish patients calls for undertaking appropriate educational activities that would facilitate earlier reporting of the patients, thus increasing their chances for recovery. Introducing preventive examinations in the regions of increased risk of testicular tumour may allow earlier diagnosis. PMID:27095941

  17. A benign maxillary tumour with malignant features.

    PubMed

    Ricalde, Rosario R; Lim, Aimee Caroline E; Lopa, Ramon Antonio B; Carnate, Jose M

    2010-06-01

    Non-specific biopsy results such as chronic inflammation, hemorrhage, necrosis can be frustrating to the clinician. This is especially true if the patient presents with clinical features suggestive of an aggressive tumour. This is a review of the clinical features, diagnostic dilemmas and surgical management of a benign maxillary mass with malignant features - a disease called hematoma-like mass of the maxillary sinus (HLMMS). Our experience with five cases will also be cited. PMID:20502750

  18. [Inflammatory myofibroblastic tumours of the bladder].

    PubMed

    Dakir, Mohamed; Taha, Abdellatif; Attar, Hicham; Sarf, Ismail; Aboutaib, Rachid; Moussaoui, Ali; Meziane, Fathi

    2004-12-01

    The inflammatory myofibroblastic tumour of the bladder is a rare benign affection that interests mainly young adults. Its etiopathogeny remains unknown, but its tumoral origin was evocated recently by Griffin (1999), incriminating a chromosomic abnormality involving the ALK gene. We will discuss the etiopathogenic, anatopathological and therapeutical aspects of this lesion for which the diagnosis is histological and the treatment remains conservative with a good prognosis. PMID:15751423

  19. Inflammatory fibroid polyp or Vanek's tumour.

    PubMed

    Paikos, D; Moschos, J; Tzilves, D; Koulaouzidis, A; Kouklakis, G; Patakiouta, F; Kontodimou, K; Tarpagos, A; Katsos, I

    2007-01-01

    We report a case of a 65-year-old woman who presented with recurrent episodes of severe, postprandial abdominal pain followed by projectile vomiting. Gastroscopy revealed a large polyp in the prepyloric region. During peristalsis, the polyp was repeatedly 'passing' through the pylorus into the duodenal bulb, hence obstructing the lumen. The polyp was eventually removed in a piecemeal fashion. Histopathologic examination revealed an inflammatory fibroid polyp (known also as Vanek's tumour). A brief review on inflammatory fibroid polyps follows. PMID:17541268

  20. Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage.

    PubMed

    Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

    2016-07-01

    Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task. We demonstrated that NAc D1- and D2-MSNs do not mediate the acquisition of the task, but that suppression of activity in D2-MSNs impairs reversal learning and increased perseverative errors. Additionally, global knockout of the dopamine D2L receptor isoform produced a similar behavioral phenotype to D2-MSN-blocked mice. These results suggest that D2L receptors and NAc D2-MSNs act to suppress the influence of previously correct behavioral strategies allowing transfer of behavioral control to new strategies. PMID:27317196

  1. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis.

    PubMed

    Huang, Hai-Peng; Pan, Hong; Wang, Hong-Feng

    2016-03-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis. PMID:27127487

  2. “Warming yang and invigorating qi” acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

    PubMed Central

    Huang, Hai-peng; Pan, Hong; Wang, Hong-feng

    2016-01-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. “Warming yang and invigorating qi” acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following “warming yang and invigorating qi” acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that “warming yang and invigorating qi” acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis. PMID:27127487

  3. Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats.

    PubMed

    Morel, Jean-Luc; Dabertrand, Fabrice; Porte, Yves; Prevot, Anne; Macrez, Nathalie

    2014-08-01

    Microgravity induces a redistribution of blood volume. Consequently, astronauts' body pressure is modified so that the upright blood pressure gradient is abolished, thereby inducing a modification in cerebral blood pressure. This effect is mimicked in the hindlimb unloaded rat model. After a duration of 8 days of unloading, Ca2+ signals activated by depolarization and inositol-1,4,5-trisphosphate intracellular release were increased in cerebral arteries. In the presence of ryanodine and thapsigargin, the depolarization-induced Ca2+ signals remained increased in hindlimb suspended animals, indicating that Ca2+ influx and Ca2+-induced Ca2+ release mechanism were both increased. Spontaneous Ca2+ waves and localized Ca2+ events were also investigated. Increases in both amplitude and frequency of spontaneous Ca2+ waves were measured in hindlimb suspension conditions. After pharmacological segregation of Ca2+ sparks and Ca2+ sparklets, their kinetic parameters were characterized. Hindlimb suspension induced an increase in the frequencies of both Ca2+ localized events, suggesting an increase of excitability. Labeling with bodipy compounds suggested that voltage-dependent Ca2+ channels and ryanodine receptor expressions were increased. Finally, the expression of the ryanodine receptor subtype 1 (RyR1) was increased in hindlimb unloading conditions. Taken together, these results suggest that RyR1 expression and voltage-dependent Ca2+ channels activity are the focal points of the regulation of Ca2+ signals activated by vasoconstriction in rat cerebral arteries with an increase of the voltage-dependent Ca2+ influx. PMID:24233561

  4. Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus).

    PubMed

    Lv, Xiaohui; Shi, Dazhao

    2012-01-01

    The effects of treatment with a combination of levonorgestrel and quinestrol (EP-1; ratio of 2:1) on reproductive hormone levels and the expression of their receptors in female Mongolian gerbils were examined. We show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreased, whereas serum estradiol (E2) and progesterone (P4) increased after EP-1 treatment. EP1 down-regulated mRNA expression of the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor (ER) βin the ovary. EP-1 up-regulated the mRNA expression of the luteinizing hormone receptor (LHR) and the progesterone receptor (PR) in the ovary as well as ERα and PR in the uterus of Mongolian gerbils. The effects were time-dependent and dose-dependent. EP-1 had no obvious effects on ERα mRNA expression in the ovary. The current study demonstrates that the effect of EP-1 on the expression of ER subtypes is tissue-specific in Mongolian gerbils. EP-1 disrupted the reproductive endocrinology of the Mongolian gerbil. These findings suggest that the effects of EP-1 on reproductive hormone levels and their receptor expression in Mongolian gerbils may be the result of synergistic actions of levonorgestrel and quinestrol, with quinestrol playing the major role. PMID:22233494

  5. TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice.

    PubMed

    Ze, Xiao; Su, Mingyu; Zhao, Xiaoyang; Jiang, Hao; Hong, Jie; Yu, Xiaohong; Liu, Dong; Xu, Bingqing; Sheng, Lei; Zhou, Qiuping; Zhou, Junling; Cui, Jingwen; Li, Kai; Wang, Ling; Ze, Yuguan; Hong, Fashui

    2016-06-01

    Titanium dioxide nanoparticles (TiO2 NPs) have been used in environmental management, food, medicine, and industry. But TiO2 NPs have been demonstrated to cross the blood-brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO2 NPs for 9 months, and the glutamate-glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly inhibited the expression of N-methyl-d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016. PMID:25411160

  6. The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status.

    PubMed

    Lin, Shin-Jen; Lin, Chang-Yi; Yang, Dong-Rong; Izumi, Kouji; Yan, Emily; Niu, Xiaodan; Chang, Hong-Chiang; Miyamoto, Hiroshi; Wang, Nancy; Li, Gonghui; Chang, Chawnshang

    2015-04-01

    The insulin sensitizers, thiazolidinediones (TZDs), have been used as anti-diabetic drugs since the discovery of their ability to alter insulin resistance through transactivation of peroxisome proliferator-activated receptors (PPARs). However, their side effects in hepatitis, cardiovascular diseases, and bladder cancer resulted in some selling restrictions in the USA and Europe. Here, we found that the potential impact of TZDs on the prostate cancer (PCa) progression might be linked to the TR4 nuclear receptor expression. Clinical surveys found that 9% of PCa patients had one allele TR4 deletion in their tumors. TZD increased cell growth and invasion in PCa cells when TR4 was knocked down. In contrast, TZD decreased PCa progression in PCa cells with wild type TR4. Mechanism dissection found that the Harvey Rat Sarcoma (HRAS) oncogene increased on TZD treatment of the TR4 knocked-down CWR22Rv1 and C4-2 cells, and interruption with HRAS inhibitor resulted in reversal of TZD-induced PCa progression. Together, these results suggest that TZD treatment may promote PCa progression depending on the TR4 expression status that may be clinically relevant since extra caution may be needed for those diabetic PCa patients receiving TZD treatment who have one allele TR4 deletion. PMID:25925376

  7. Effect of Increased Cyclic AMP Concentration on Muscle Protein Synthesis and Beta-Adrenergic Receptor Expression in Chicken Skeletal Muscle Cells in Culture

    NASA Technical Reports Server (NTRS)

    Young, R. B.; Vaughn, J. R.; Bridge, K. Y.; Smith, C. K.

    1998-01-01

    Analogies of epinephrine are known to cause hypertrophy of skeletal muscle when fed to animals. These compounds presumably exert their physiological action through interaction with the P-adrenergic receptor. Since the intracellular signal generated by the Beta-adrenergic receptor is cyclic AMP (cAMP), experiments were initiated in cell culture to determine if artificial elevation of cAMP by treatment with forskolin would alter muscle protein metabolism and P-adrenergic receptor expression. Chicken skeletal muscle cells after 7 days in culture were treated with 0.2-30 micrometers forskolin for a total of three days. At the end of the treatment period, both the concentration of cAMP and the quantity of myosin heavy chain (MHC) were measured. Concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. In contrast, the quantity of MHC was increased approximately 50% above control cells at 0.2 micrometers forskolin, but exhibited a gradual decline at higher levels of forskolin so that the quantity of MHC in cells treated with 30 micrometers forskolin was not significantly different from controls. Curiously, the intracellular concentration of cAMP which elicited the maximum increase in the quantity of MHC was only 40% higher than cAMP concentration in control cells.

  8. Dawn-song onset coincides with increased HVC androgen receptor expression but is decoupled from high circulating testosterone in an equatorial songbird.

    PubMed

    Quispe, René; Sèbe, Frédéric; da Silva, Maria Luisa; Gahr, Manfred

    2016-03-15

    The song of songbirds is a testosterone-sensitive behavior that is controlled by brain regions expressing androgen receptors. At higher latitudes, seasonal singing is stimulated by increasing day-length and elevated circulating testosterone. However, a large number of songbird species inhabit equatorial regions under a nearly constant photoperiod, and the neuroendocrine mechanisms of seasonal song in these species have rarely been investigated. We studied males from an equatorial population of the silver-beaked tanager (Ramphocelus carbo), an Amazonian songbird. We found seasonality in dawn-song behavior, which was displayed continuously for more than half a year throughout an extended breeding territoriality stage. The seasonal activation of dawn-song was correlated with an increased area of androgen receptor expression in HVC, a major brain area of song control. However, testosterone levels remained low for several weeks after activation of dawn-song. Circulating levels of testosterone were elevated only later in the breeding season, coinciding with a higher dawn-song output and with the mating period. Our results suggest that the seasonal activation of dawn-song and territoriality involves an increase of androgen target cells in HVC. This mechanism could potentially function to circumvent adverse effects of high testosterone levels in a species with an extended breeding season. PMID:26752610

  9. Evaluation and Validation of the Detection of soluble Triggering Receptor Expressed on Myeloid Cells 1 by Enzyme-linked immunosorbent Assay

    PubMed Central

    Hasibeder, Astrid; Stein, Pamela; Brandwijk, Ricardo; Schild, Hansjörg; Radsak, Markus P.

    2015-01-01

    Triggering receptor expressed on myeloid cells (TREM)-1 plays an important role in innate immune responses and is upregulated under infectious as well as non-infectious conditions. In addition, a soluble TREM-1 variant (sTREM-1) is detectable in sera or bronchoalveolar-lavage fluids from patients. Currently, various studies are difficult to compare, since the methods of detection by enzyme-linked immunosorbent assays (ELISA) vary among different research groups. In this study, we compared three different s-TREM-1 specific ELISAs and identified individual assay characteristics finding notable differences in sTREM-1 concentrations in part depending on the employed buffers. Investigating potential confounding factors for sTREM-1 detection, serum heat-inactivation (HI) showed improved recovery compared to non-HI (NHI) serum, reproducible by addition of complement and re-heat-inactivation. Hence we identified complement as a heat-sensitive confounder in some sTREM-1 ELISAs. We conclude that it is difficult to directly compare data of several studies, in particular if different ELISAs are engaged. Immunoassays for research use only are in general hampered by lack of standardization. Further standardization is needed until sTREM-1 ELISA is capable for better reproducibility of studies and clinical application. PMID:26480887

  10. Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras.

    PubMed

    Papapetrou, Eirini P; Kovalovsky, Damian; Beloeil, Laurent; Sant'angelo, Derek; Sadelain, Michel

    2009-01-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression by targeting complementary sequences, referred to as miRNA recognition elements (MREs), typically located in the 3' untranslated region of mRNAs. miR-181a is highly expressed in developing thymocytes and markedly downregulated in post-thymic T cells. We investigated whether endogenous miR-181a can be harnessed to segregate expression of chimeric antigen receptors (CARs) and TCRs between developing and mature T cells. Lentiviral-encoded antigen receptors were tagged with a miR-181a-specific MRE and transduced into mouse BM cells that were used to generate hematopoietic chimeras. Expression of a CAR specific for human CD19 (hCD19) was selectively suppressed in late double-negative and double-positive thymocytes, coinciding with the peak in endogenous miR-181a expression. Receptor expression was fully restored in post-thymic resting and activated T cells, affording protection against a subsequent challenge with hCD19+ tumors. Hematopoietic mouse chimeras engrafted with a conalbumin-specific TCR prone to thymic clonal deletion acquired peptide-specific T cell responsiveness only when the vector-encoded TCR transcript was similarly engineered to be subject to regulation by miR-181a. These results demonstrate the potential of miRNA-regulated transgene expression in stem cell-based therapies, including cancer immunotherapy. PMID:19033646

  11. Cinnamomum camphora Seed Kernel Oil Improves Lipid Metabolism and Enhances β3-Adrenergic Receptor Expression in Diet-Induced Obese Rats.

    PubMed

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Wen, Xuefang; Yu, Ping; Gong, Deming

    2016-06-01

    The effects of dietary Cinnamomum camphora seed kernel oil (CCSKO) containing medium-chain triacylglycerols on lipid metabolism and mRNA and protein expression of β-3 adrenergic receptor in adipose tissue were studied in diet-induced obese rats. High fat food-induced obese rats were randomly divided into CCSKO group, Lard group, Soybean oil (SOY) group and naturally restoring group (n = 10). Rats fed with low fat food were used as a normal control group. Significant decreases in body mass and abdominal fat mass/body mass after 12 weeks were found in CCSKO group as compared with Lard and SOY groups (p < 0.05). Levels of blood total cholesterol (TC), triglyceride, free fatty acid, fasting insulin and insulin resistance in the CCSKO group were decreased significantly, and noradrenaline level and insulin sensitivity index in the CCSKO group were significantly higher than other groups. Meanwhile liver TC and triglyceride levels in the CCSKO group were also decreased markedly. Expression levels of β3-adrenergic receptor mRNA and protein were higher in CCSKO group than in Lard and SOY groups. These results suggest that CCSKO may contribute to reduction of the body fat mass, promote lipid metabolism and up-regulate β3-adrenergic receptor expression in high fat diet-induced obese rats. PMID:27068065

  12. Differential relationships between D1 and D2 dopamine receptor expression in the medial preoptic nucleus and sexually-motivated song in male European starlings (Sturnus vulgaris).

    PubMed

    DeVries, M S; Cordes, M A; Stevenson, S A; Riters, L V

    2015-08-20

    Converging data in songbirds support a central role for the medial preoptic nucleus (POM) in motivational aspects of vocal production. Recent data suggest that dopamine in the POM plays a complex modulatory role in the production of sexually-motivated song and that an optimal level of dopamine D1 receptor stimulation is required to facilitate singing behavior. To further explore this possibility, we used quantitative real-time PCR to examine relationships between mRNA expression of D1 as well as D2 receptors in the POM (and also the lateral septum and Area X) and sexually-motivated singing behavior in male European starlings. Results showed that both males with the highest and lowest D1 expression in the POM sang significantly less than males with intermediate levels of expression. Furthermore, singing behavior rose linearly in association with increasing levels of D1 expression in POM but dropped abruptly, such that individuals with D1 expression values higher than the mean sang very little. Analysis of birds with low and intermediate levels of D1 expression in POM revealed strong positive correlations between D1 expression and song but negative relationships between D2 receptor expression and song. These findings support prior work suggesting an optimal level of POM D1 receptor stimulation best facilitates sexually-motivated singing behavior. Results also suggest that D2 receptors may work in opposition to D1 receptors in POM to modify vocal production. PMID:26079111

  13. Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy.

    PubMed

    Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke; Hirobe, Sachiko; Nakagawa, Shinsaku; Okada, Naoki

    2016-04-22

    Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period of pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. PMID:26993168

  14. Role of tumour angiogenesis in haematological malignancies.

    PubMed

    Medinger, Michael; Passweg, Jakob

    2014-01-01

    Tumour angiogenesis plays a key role in the pathogenesis and progression of haematological malignancies. Thereby, pro- and anti-angiogenic growth factors and cytokines regulate the angiogenic process. The most important growth factor, vascular endothelial growth factor (VEGF) and its signaling through its receptors 1 and 2, is not only involved in solid tumours, but there is also emerging evidence that tumour progression in haematological malignancies also depends on the induction of new blood vessel formation. The evidence supporting this theory includes the finding of increased bone marrow microvessel density and increased levels of plasma pro-angiogenic cytokines. Leukaemia cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype. The pathophysiology of leukaemia induced angiogenesis involves both direct production of angiogenic cytokines by leukaemia cells and their interaction with bone marrow microenvironment. The inhibition of VEGF signalling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully used for the treatment of different cancer entities, and multiple new drugs are being tested. This review summarises recent advances in the basic understanding of the role of angiogenesis in haematological malignancies and the translation of such basic findings into clinical studies. PMID:25375891

  15. Familial syndromes associated with neuroendocrine tumours

    PubMed Central

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

    2015-01-01

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

  16. [Ovarian yolk sac tumour: general review].

    PubMed

    Even, Caroline; Lhommé, Catherine; Duvillard, Pierre; Morice, Philippe; Balleyguier, Corinne; Pautier, Patricia; Troalen, Frédéric; de La Motte Rouge, Thibault

    2011-08-01

    Ovarian yolk sac tumour (OYST) is a very rare malignancy arising most often in young women. Preoperative clinical, biological (alpha-foetoprotein) and radiological findings should help to establish the diagnosis of OYST, in order to propose adequate surgical treatment. The aim of surgery is to remove the primary tumour, to obtain an accurate histological diagnosis and to assess the disease extent. In young women, fertility-sparing surgery should be performed, in order to preserve the possibility of pregnancy later on. Chemotherapy has substantially modified the prognosis of these tumours, and practically all patients will be cured. The overall 5-year survival rate is 94% when patients are treated with BEP chemotherapy. Depending on the clinical situation, two to four cycles of the BEP regimen should be administered after surgery. Identification of prognostic factors may help to propose risk-adapted treatment in order to increase the cure rate in patients with a poor prognosis and to decrease toxicity in patients with a low risk of relapse. Fertility preservation represents a major objective in women treated for OYSTs. PMID:21708513

  17. Tumour exosome integrins determine organotropic metastasis.

    PubMed

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

  18. Diagnosis and surgical treatment of retroperitoneal tumours.

    PubMed

    Testini, M; Catalano, G; Macarini, L; Paccione, F

    1996-01-01

    The authors examine the various techniques for diagnosing Retroperitoneal Tumours (RPT) and analyse the results of the surgical treatment performed. Between March 1987 and February 1991, 20 patients with RPT (6 benign and 14 malignant forms) were observed in our Institution. CT and NMR revealed more diagnostic accuracy than other techniques (100%), while NMR had greater accuracy than CT in predictly resectability preoperatively (100% vs. 80.0%, respectively). A total of 26 laparotomies were performed: 20 for primary neoplasms and 6 for recurrent tumours. Exeresis of the mass was performed in 18/20 (90%) patients. Mean follow-up was 57.6 months (84-36). The benign forms had no recurrence. In malignant cases the disease recurred in 58.3% of the cases after an interval varying from 10 to 59 months. Overall mean survival of the 12 patients with malignant tumours subjected to resection was 58.3%. The 1- and 3-year survival rates were 91.7% and 58.3% respectively. Prognosis in malignant RPT is still very poor. PMID:8803715

  19. Cell metabolism, tumour diagnosis and multispectral FLIM

    NASA Astrophysics Data System (ADS)

    Rück, A.; Hauser, C.; Lorenz, S.; Mosch, S.; Rotte, S.; Kessler, M.; Kalinina, S.

    2013-02-01

    Fluorescence guided diagnosis of tumour tissue is in many cases insufficient, because false positive results are interfering with the outcome. Discrimination between tumour and inflammation could be therefore difficult. Improvement of fluorescence diagnosis through observation of cell metabolism could be the solution, which needs a detailed understanding of the origin of autofluorescence. However, a complex combination of fluorophores give rise to the emission signal. Also in PDD (photodynamic diagnosis) different photosensitizer metabolites contribute to the fluorescence signal. Therefore, the fluorescence decay in many cases does not show a simple monoexponential profile. In those cases a considerable improvement could be achieved when time-resolved and spectral-resolved techniques are simultaneously incorporated. The discussion will focus on the detection of NADH, FAD and 5-ALA induced porphyrins. With respect to NADH and FAD the discrimination between protein bound and free coenzyme was investigated with multispectral FLIM in normal oral keratinocytes and squamous carcinoma cells from different origin. The redox ratio, which can be correlated with the fluorescence lifetimes of NADH and FAD changed depending on the state of the cells. Most of the investigations were done in monolayer cell cultures. However, in order to get information from a more realistic in vivo situation additionally the chorioallantoismembrane (CAM) of fertilized eggs was used where tumour cells or biopsies were allowed to grow. The results of theses measurements will be discussed as well.

  20. Tumour promoter activity in Malaysian Euphorbiaceae.

    PubMed Central

    Norhanom, A. W.; Yadav, M.

    1995-01-01

    Herbal medication has been practised by the rural Malaysian Malays for a long time. However, the long-term side-effects have never been studied. In the present study, 48 species of Euphorbiaceae were screened for tumour-promoter activity by means of an in vitro assay using a human lymphoblastoid cell line harbouring the Epstein-Barr virus (EBV) genome. Twenty-seven per cent (13 out of 48) of the species tested were found to be positive, and in four species, namely Breynia coronata Hk.f, Codiaeum variegatum (L) Bl, Euphorbia atoto and Exocoecaria agallocha, EBV-inducing activity was observed when the plant extracts were tested at low concentrations of between 0.2 and 1.2 micrograms ml-1 in cell culture. This observation warrants attention from the regular users of these plants because regular use of plants with tumour-promoting activity could well be an aetiological factor for the promotion of tumours among rural Malaysian Malays. PMID:7710943

  1. Clinical tumour markers in ovarian cancer.

    PubMed

    Mazurek, A; Nikliński, J; Laudański, T; Pluygers, E

    1998-02-01

    Within past few years, the measurement of serological, histochemical and molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting markers in ovarian cancer. CA 125, CA 19.9, TATI, CASA, CEA, TPA, TPS and CYFRA21-1 are now the most widely used serological tumour markers for management of ovarian cancer patients. Ras oncogenes, C-erb2 proto-oncogene, p53 suppressor gene and Bcl-2 oncogene are examples of currently used molecular genetic markers. As histochemical markers-proliferation markers, flow cytometric analysis, thymidine labelling index, Ki-67 nuclear antigen or differentiation markers are nowadays the ones most often determined. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. Numerous tumour markers characterized in this paper have been recognized as promising prognostic factors. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies; nevertheless to validate these factors, prospective studies of a large patient population are needed. PMID:9511849

  2. Tumour exosome integrins determine organotropic metastasis

    PubMed Central

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-01-01

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

  3. Imatinib treatment for gastrointestinal stromal tumour (GIST)

    PubMed Central

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734

  4. [Epidemiology and risk factors of testicular tumours].

    PubMed

    Kozłowski, Piotr; Starosławska, Elżbieta; Szumiło, Justyna; Jankiewicz, Małgorzata; Kozłowska, Magdalena; Burdan, Franciszek

    2016-04-01

    Testicular tumours are rare neoplasms, which most commonly affects men aged 25 to 35 years. Among young adult males it is the most common cause of testicular swelling. In recent decades, the number of cases of testicular tumours has greatly increased. The most significant predisposing factors are cryptorchidism and some endocrine disorders, especially increased levels of gonadotropins and female sex hormones. Testicular trauma, inguinal hernia, extreme values of body mass index (BMI), high-calorie diet rich in dairy products as well as high social status are also regarded as risk factors. Furthermore, some chromosomal abnormalities like increased number of chromosomes 7, 8. 12, 21 and X, loss of chromosomes 4, 5, 11, 13, 18, or Y, mutation in the gene Xq27; as well as multiplied copy of the gene i(12p) are associated with tumor development. It has been proven that high testosterone levels and regular physical activity may prevent testicular tumours. Since one of the first sign the lesion is often a lump or swelling of the testis and the appearance of abnormal structure in the scrotum routine testicular self-examination seems to be important in early detection. In all suspected cases an immediate ultrasound examination of both testicles is highly recommended. It is also advised to conduct a computerized tomography (CT) and a positron emission tomography (PET) scan for staging of the tumor to select the best mode of treatment. PMID:27137819

  5. Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis.

    PubMed

    Yin, Shu-Yi; Jian, Feng-Yin; Chen, Yung-Hsiang; Chien, Shih-Chang; Hsieh, Mao-Chih; Hsiao, Pei-Wen; Lee, Wen-Hwa; Kuo, Yueh-Hsiung; Yang, Ning-Sun

    2016-01-01

    Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities. PMID:27089063

  6. Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis

    PubMed Central

    Yin, Shu-Yi; Jian, Feng-Yin; Chen, Yung-Hsiang; Chien, Shih-Chang; Hsieh, Mao-Chih; Hsiao, Pei-Wen; Lee, Wen-Hwa; Yang, Ning-Sun

    2016-01-01

    Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities. PMID:27089063

  7. Local tumour hyperthermia as immunotherapy for metastatic cancer

    PubMed Central

    Toraya-Brown, Seiko; Fiering, Steven

    2014-01-01

    Abstract Local tumour hyperthermia for cancer treatment is currently used either for ablation purposes as an alternative to surgery or less frequently, in combination with chemotherapy and/or radiation therapy to enhance the effects of those traditional therapies. As it has become apparent that activating the immune system is crucial to successfully treat metastatic cancer, the potential of boosting anti-tumour immunity by heating tumours has become a growing area of cancer research. After reviewing the history of hyperthermia therapy for cancer and introducing methods for inducing local hyperthermia, this review describes different mechanisms by which heating tumours can elicit anti-tumour immune responses, including tumour cell damage, tumour surface molecule changes, heat shock proteins, exosomes, direct effects on immune cells, and changes in the tumour vasculature. We then go over in vivo studies that provide promising results showing that local hyperthermia therapy indeed activates various systemic anti-tumour immune responses that slow growth of untreated tumours. Finally, future research questions that will help bring the use of local hyperthermia as systemic immunotherapy closer to clinical application are discussed. PMID:25430985

  8. Site-specific volumetric analysis of lung tumour motion

    NASA Astrophysics Data System (ADS)

    Pepin, Eric W.; Wu, Huanmei; Sandison, George A.; Langer, Mark; Shirato, Hiroki

    2010-06-01

    The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes (<50 mm3), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm3). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.

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

    PubMed Central

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

    2015-01-01

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

  10. Synthesis, characterization and systematic comparison of FITC-labelled GnRH-I, -II and -III analogues on various tumour cells.

    PubMed

    Murányi, József; Gyulavári, Pál; Varga, Attila; Bökönyi, Györgyi; Tanai, Henriette; Vántus, Tibor; Pap, Domonkos; Ludányi, Krisztina; Mező, Gábor; Kéri, György

    2016-08-01

    Targeted tumour therapy is the focus of recent cancer research. Gonadotropin-releasing hormone (GnRH) analogues are able to deliver anticancer agents selectively into tumour cells, which highly express GnRH receptors. However, the effectiveness of different analogues as targeting moiety in drug delivery systems is rarely compared, and the investigated types of cancer are also limited. Therefore, we prepared selectively labelled, fluorescent derivatives of GnRH-I, -II and -III analogues, which were successfully used for drug targeting. In this manuscript, we investigated these analogues' solubility, stability and passive membrane permeability and compared their cellular uptake by various cancer cells. We found that these labelled GnRH conjugates provide great detectability, without undesired cytotoxicity and passive membrane permeability. The introduced experiments with these conjugates proved their reliable tracking, quantification and comparison. Cellular uptake efficiency was studied on human breast, colon, pancreas and prostate cancer cells (MCF-7, HT-29, BxPC-3, LNCaP) and on dog kidney cells (Madin-Darby canine kidney). Each of the three conjugates was taken up by GnRH-I receptor-expressing cells, but the different cells preferred different analogues. Furthermore, we demonstrated for the first time the high cell surface expression of GnRH-I receptors and the effective cellular uptake of GnRH analogues on human pharynx tumour (Detroit-562) cells. In summary, our presented results detail that the introduced conjugates could be innovative tools for the examination of the GnRH-based drug delivery systems on various cells and offer novel information about these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27443981

  11. Canine cutaneous spindle cell tumours with features of peripheral nerve sheath tumours: a histopathological and immunohistochemical study.

    PubMed

    Gaitero, L; Añor, S; Fondevila, D; Pumarola, M

    2008-07-01

    In veterinary medicine, the term peripheral nerve sheath tumour is usually restricted to neoplasms that are closely associated with an identified nerve. Thirty-three cases of canine cutaneous tumours previously classified as spindle cell tumours with features resembling peripheral nerve sheath tumours were examined. Two histological patterns were identified: dense areas of spindle shaped cells resembling the Antoni A pattern and less cellular areas with more pleomorphic cells resembling the Antoni B pattern. Immunohistochemically, all tumours uniformly expressed vimentin and 15/33 (45.4%) had scattered and patchy expression of S-100. Laminin expression was found in 25/33 (75.7%) tumours and collagen IV labelling occurred in 14/33 (42.4%). Expression of protein gene product 9.5 was detected in 31/33 (93.9%) of tumours and neuron specific enolase labelling was present in 27/33 (81.8%). Glial fibrillary acidic protein was only expressed within the cytoplasm of some large multinucleated cells in one tumour. These findings suggest that any cutaneous tumour with one of the two histopathological patterns described above should be described as a cutaneous peripheral nerve sheath tumour and that expression of S-100, laminin and collagen IV may be used to define a schwannoma. PMID:18514218

  12. Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours.

    PubMed

    Zaffryar-Eilot, Shelly; Marshall, Derek; Voloshin, Tali; Bar-Zion, Avinoam; Spangler, Rhyannon; Kessler, Ofra; Ghermazien, Haben; Brekhman, Vera; Suss-Toby, Edith; Adam, Dan; Shaked, Yuval; Smith, Victoria; Neufeld, Gera

    2013-10-01

    Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours. PMID:23828904

  13. The ratio of maximum percent tumour accumulations of the pretargeting agent and the radiolabelled effector is independent of tumour size.

    PubMed

    Liu, Guozheng; Dou, Shuping; Liang, Minmin; Chen, Xiangji; Rusckowski, Mary; Hnatowich, Donald J

    2009-11-01

    Our previous studies have indicated that the optimal dosage ratio of pretargeting antibody to effector is proportional to their maximum percent tumour accumulations (MPTAs). This study quantitatively describes how both MPTAs and their ratio change with tumour size, to simplify pretargeting optimisation when tumour size varies. The CC49 antibody dosages below saturation of the tumour antigen level were first examined for the LS174T tumour mouse model. Then the MPTAs of the antibody in mice bearing tumours of different sizes were determined, always at antibody dosages below antigen saturation. Historical data from this laboratory were used to collect the MPTAs of the (99m)Tc-cMORF effector for different tumour sizes, always at effector dosages below that required to saturate the MORF in tumour. The MPTAs versus tumour sizes for both the antibody and the effector were fitted non-linearly. The best fit of the antibody MPTA (Y(antibody)) with tumour size (x) in grams was Y(antibody)=19.00 x(-0.65) while that for the effector was Y(effector)=4.51x(-0.66). Thus, even though the MPTAs of both vary with tumour size, the ratio (Y(antibody)/Y(effector)) is a constant at 4.21. In conclusion, the MPTA ratio of the antibody to the effector was found to be constant with tumour size, an observation that will simplify pretargeting optimisation because remeasurement of the optimum dosage ratio for different tumour sizes can be avoided. Theoretical considerations also suggest that this relationship may be universal for alternative antibody/effector pairs and for different target models, but this must be experimentally confirmed. PMID:19811906

  14. Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation.

    PubMed

    Osmond, Allison; Filter, Emily; Joseph, Mariamma; Inculet, Richard; Kwan, Keith; McCormack, David

    2016-01-01

    Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment. We present an unusual case of endobronchial carcinoid tumour with extensive ossification in a 45-year-old male. Preliminary intraoperative diagnosis was achieved through the alternative use of cytology scrape smears. The final diagnosis was confirmed after decalcification of the tumour. The prognostic implications of heavily ossified carcinoid tumours remain elusive. Long-term clinical follow-up of these patients is recommended. PMID:27610135

  15. Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation

    PubMed Central

    Filter, Emily; Joseph, Mariamma; Inculet, Richard; Kwan, Keith; McCormack, David

    2016-01-01

    Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment. We present an unusual case of endobronchial carcinoid tumour with extensive ossification in a 45-year-old male. Preliminary intraoperative diagnosis was achieved through the alternative use of cytology scrape smears. The final diagnosis was confirmed after decalcification of the tumour. The prognostic implications of heavily ossified carcinoid tumours remain elusive. Long-term clinical follow-up of these patients is recommended. PMID:27610135

  16. Extra gonadal sclerosing stromal tumour in the transverse mesocolon.

    PubMed

    Mensah, Samuel; Kyei, Ishmael; Ohene-Yeboah, Michael; Adjei, Ernest

    2016-03-01

    Sclerosing stromal tumour (SST) is a rare benign sex cord stromal tumour of the ovary. We report a case of sclerosing stromal tumour of the mesentery in a 32-year-old Para one who presented with intra abdominal mass, menstrual irregularity and secondary infertility. Histopathology and immunohistochemistry of the completely excised tumour was consistent with sclerosing stromal tumour, immunoreactive only to vimentin. No ovarian tissue was found in the sectioned tumour. Her menses became regular and she conceived 3 months after complete excision and delivered after 9 months. Hormonal assay was not done because SST was least suspected. From literature this is the first case of SST in the transverse mesocolon reported in the West African subregion, and may probably be one of the rare cases of hormonally active SST. PMID:27605726

  17. Tumour-induced osteomalacia: An emergent paraneoplastic syndrome.

    PubMed

    Alonso, Guillermo; Varsavsky, Mariela

    2016-04-01

    Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies. PMID:26718193

  18. Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis.

    PubMed

    Jung, Younghun; Kim, Jin Koo; Shiozawa, Yusuke; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Krebsbach, Paul H; Keller, Evan T; Pienta, Kenneth J; Taichman, Russell S

    2013-01-01

    Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis. PMID:23653207

  19. Imaging of rare medullary adrenal tumours in adults.

    PubMed

    Maciel, C A; Tang, Y Z; Coniglio, G; Sahdev, A

    2016-05-01

    Although adrenal medullary tumours are rare, they have important clinical implications. They form a heterogeneous group of tumours, ranging from benign, non-secretory, incidental masses to hormonally active tumours presenting acutely, or malignant tumours with disseminated disease and a poor prognosis. Increasingly, benign masses are incidentally detected due to the widespread use of imaging and routine medical check-ups. This review aims to illustrate the multimodality imaging appearances of rare adrenal medullary tumours, excluding the more common phaeochromocytomas, with clues to the diagnosis and to summarise relevant epidemiological and clinical data. Careful correlation of clinical presentation, hormone profile, and various imaging techniques narrow the differential diagnosis. Image-guided percutaneous adrenal biopsy can provide a definitive diagnosis, allowing for conservative management in selected cases. A close collaboration between the radiologist, endocrinologist, and surgeon is of the utmost importance in the management of these tumours. PMID:26944698

  20. Tumour-associated hypoglycaemia in a murine cachexia model.

    PubMed Central

    McDevitt, T. M.; Tisdale, M. J.

    1992-01-01

    Animals bearing a cachexia-inducing tumour, the MAC16 adenocarcinoma, showed a progressive decrease in blood glucose levels with increasing weight loss, while animals bearing a histologically similar tumour, the MAC13 adenocarcinoma, showed no change in either body weight or blood glucose levels with growth of the tumour. The effect of the MAC16 tumour on blood glucose levels appeared to be unrelated to food intake, glucose consumption by the tumour, or to the production of increased levels of IGF-I and IGF-II mRNA by the tumour cells. The relationship between the induction of cachexia and alteration in blood glucose levels remains unknown. Images Figure 4 Figure 5 PMID:1358167

  1. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas

    NASA Astrophysics Data System (ADS)

    Wiesner, Thomas; He, Jie; Yelensky, Roman; Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S.; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T.; Stephens, Philip J.; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumours with distinctive histopathological features. They include benign tumours (Spitz naevi), malignant tumours (spitzoid melanomas) and tumours with borderline histopathological features and uncertain clinical outcome (atypical Spitz tumours). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signalling pathways, are tumourigenic and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanomas.

  2. [Perioperative management of intracranial tumours: the neurosurgeon's role].

    PubMed

    Polo-Torres, C; Moscote-Salazar, L R; Alvis-Miranda, H R; Villa-Delgado, R

    2013-01-01

    The perioperative management of patients with brain tumours is a challenge for the neurosurgeon and the entire surgical team. The treating physician should consider factors such as the type of tumour, extent of disease, treatment received, the presence of comorbidities and prognosis of the disease itself. The successful execution of all aspects involved in perioperative management in patients with brain tumours will help prolong the life and improve the quality of life of patients. PMID:24008533

  3. Mixed tumour of salivary gland type of the male breast.

    PubMed

    Simha, M R; Doctor, V M; Udwadia, T E

    1992-03-01

    Benign breast tumours with a mixed cartilaginous and epithelial component are distinctly rare as evident from the literature. A case of Mixed Tumour of the breast presenting pre-operatively as a hard mass in a 65 year old male is reported. Histologically, it was composed of a mixture of benign cartilage, myoepithelial cells, tubules and a myxoid stroma in fat. A brief review of cartilage bearing lesions and mixed tumour in the mammary region is discussed. PMID:1328037

  4. Giant Appendiceal Leiomyosarcoma: A Rare and Unusual Tumour

    PubMed Central

    Natalia, Christine; Koh, Cherry E.; Lee, Peter J.

    2011-01-01

    Appendiceal tumours are uncommon but may be present in 0.9–1.4% of all appendicectomy specimens. While carcinoid tumours and adenocarcinomas comprise the majority of appendiceal tumours, rarely, lymphomas or sarcomas may also present in the appendix. Appendiceal leiomyosarcomas are rare, and to date, only a handful of cases have been reported. The current paper presents a case of giant appendiceal leiomyosarcoma followed by a review of the literature. PMID:22606577

  5. Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.

    PubMed

    Rezin, Gislaine T; Petronilho, Fabricia C; Araújo, João H; Gonçalves, Cinara L; Daufenbach, Juliana F; Cardoso, Mariane R; Roesler, Rafael; Schwartsmann, Gilberto; Dal-Pizzol, Felipe; Streck, Emilio L

    2011-03-01

    The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis. PMID:21138529

  6. Intravenous infusion of gastrin-releasing peptide-27 and bombesin in rats reveals differential effects on meal size and intermeal interval length

    PubMed Central

    Washington, Martha C.; Salyer, Sarah; Aglan, Amnah H.; Sayegh, Ayman I.

    2016-01-01

    We have previously shown that the intraperitoneal (i.p) administration of gastrin-releasing peptide-27 (GRP-27) or bombesin (BN) (at 0.21, 0.41 and 1.03 nmol/kg) reduces meal size (MS) and prolongs the intermeal interval (IMI). Here, we hypothesized that the intravenous (i.v) administration of the same doses of GRP-27 and BN will be as effective as the i.p administration in evoking these feeding responses. To test this hypothesis, we administered GRP-27 and BN i.v and measured first MS (10% sucrose), IMI, satiety ratio (SR, IMI/MS) and second MS in overnight food-deprived but not water-deprived male Sprague Dawley rats. We found that (1) only GRP-27 reduced the first MS, (2) BN prolonged the IMI, (3) GRP-27 and BN increased the SR and (4) only BN reduced the size of the second meal. Contrary to our hypothesis, the i.v administration of GRP-27 and BN affected the MS and IMI differently than did the i.p administration. In conclusion, this pharmacological study suggests that the MS and IMI are regulated at different sites. PMID:24291388

  7. Electrophysiological properties of brain-natriuretic peptide- and gastrin-releasing peptide-responsive dorsal horn neurons in spinal itch transmission.

    PubMed

    Kusube, Fumiya; Tominaga, Mitsutoshi; Kawasaki, Hiroaki; Yamakura, Fumiyuki; Naito, Hisashi; Ogawa, Hideoki; Tomooka, Yasuhiro; Takamori, Kenji

    2016-08-01

    Spinal itch transmission has been reported to be mediated by at least two neuronal populations in spinal dorsal horn, neurons expressing brain-natriuretic peptide (BNP) receptor (Npra) and gastrin-releasing peptide (GRP) receptor (GRPR). Although Npra-expressing neurons were shown to be upstream of GRPR- expressing neurons in spinal itch transmission, the roles of BNP and GRP in the spinal neurotransmission of histamine-dependent and -independent itch remains unclear. Using in vivo electrophysiology and behavior analysis, this study examined the responses of chloroquine (histamine-independent pruritogen)-responsive and histamine-responsive dorsal horn neurons to spinal applications of BNP and GRP. Electrophysiologically, 9.5% of chloroquine-responsive neurons responded to BNP, 33.3% to GRP, and 4.8% to both, indicating that almost half of chloroquine-responsive neurons were unresponsive to both BNP and GRP. In contrast, histamine-responsive neurons did not respond to spinal BNP application, whereas 30% responded to spinal GRP application, indicating that 70% of histamine-responsive neurons were unresponsive to both BNP and GRP. Behavioral analyses showed differences in the time-course and frequency of scratching responses evoked by intrathecal BNP and GRP. These findings provide evidence that most BNP-Npra and GRP-GRPR signaling involve different pathways of spinal itch transmission, and that multiple neurotransmitters, in addition to BNP and GRP, are involved in spinal itch transmission. The electrophysiological results also suggest that spinal BNP contributes little to histaminergic itch directly. PMID:27235577

  8. Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

    PubMed Central

    Gutierrez-Mecinas, Maria; Polgár, Erika; Todd, Andrew J

    2016-01-01

    Background Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway. PMID:27270268

  9. Evolutionarily conserved organization of the dopaminergic system in lamprey: SNc/VTA afferent and efferent connectivity and D2 receptor expression.

    PubMed

    Pérez-Fernández, Juan; Stephenson-Jones, Marcus; Suryanarayana, Shreyas M; Robertson, Brita; Grillner, Sten

    2014-12-01

    The dopaminergic system influences motor behavior, signals reward and novelty, and is an essential component of the basal ganglia in all vertebrates including the lamprey, one of the phylogenetically oldest vertebrates. The intrinsic organization and function of the lamprey basal ganglia is highly conserved. For instance, the direct and indirect pathways are modulated through dopamine D1 and D2 receptors in lamprey and in mammals. The nucleus of the tuberculum posterior, a homologue of the substantia nigra pars compacta (SNc)/ventral tegmental area (VTA) is present in lamprey, but only scarce data exist about its connectivity. Likewise, the D2 receptor is expressed in the striatum, but little is known about its localization in other brain areas. We used in situ hybridization and tracer injections, both in combination with tyrosine hydroxylase immunohistochemistry, to characterize the SNc/VTA efferent and afferent connectivity, and to relate its projection pattern with D2 receptor expression in particular. We show that most features of the dopaminergic system are highly conserved. As in mammals, the direct pallial (cortex in mammals) input and the basal ganglia connectivity with the SNc/VTA are present as part of the evaluation system, as well as input from the tectum as the evolutionary basis for salience/novelty detection. Moreover, the SNc/VTA receives sensory information from the olfactory bulbs, optic tectum, octavolateral area, and dorsal column nucleus, and it innervates, apart from the nigrostriatal pathway, several motor-related areas. This suggests that the dopaminergic system also contributes to the control of different motor centers at the brainstem level. PMID:24942187

  10. Dendritic Cells Expressing Triggering Receptor Expressed on Myeloid Cells-1 Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis.

    PubMed

    Rai, Vikrant; Rao, Velidi H; Shao, Zhifei; Agrawal, Devendra K

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory cells, including T-lymphocytes, dendritic cells (DCs) and macrophages that are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. In atherosclerotic tissue the number of DCs increases with the progression of the lesion and produce several inflammatory cytokines and growth factors. Triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role in inflammation. However, relationship of DCs and the role of TREM-1 with the stability of atherosclerotic plaques have not been examined. In this study, we investigated the heterogeneity of the plaque DCs, myeloid (mDC1 and mDC2) and plasmacytoid (pDCs), and examined the expression of TREM-1 and their co-localization with DCs in the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. We found increased expression of HLA-DR, fascin, and TREM-1 and decreased expression of TREM-2 and α-smooth muscle actin in S compared to AS atherosclerotic carotid plaques. Both TREM-1 and fascin were co-localized suggesting increased expression of TREM-1 in plaque DCs of S compared to AS patients. These data were supported by increased mRNA transcripts of TREM-1 and decreased mRNA transcripts of TREM-2 in carotid plaques of S compared to AS patients. There was higher density of both CD1c+ mDC1 and CD141+ mDC2 in the carotid plaques from AS compared to S patients, where as the density of CD303+ pDCs were higher in the carotid plaques of S compared to AS patients. These findings suggest a potential role of pDCs and TREM-1 in atherosclerotic plaque vulnerability. Thus, newer therapies could be developed to selectively block TREM-1 for stabilizing atherosclerotic plaques. PMID:27148736

  11. Compromised NMDA/Glutamate Receptor Expression in Dopaminergic Neurons Impairs Instrumental Learning, But Not Pavlovian Goal Tracking or Sign Tracking1,2,3

    PubMed Central

    James, Alex S.; Pennington, Zachary T.; Tran, Phu

    2015-01-01

    Abstract Two theories regarding the role for dopamine neurons in learning include the concepts that their activity serves as a (1) mechanism that confers incentive salience onto rewards and associated cues and/or (2) contingency teaching signal reflecting reward prediction error. While both theories are provocative, the causal role for dopamine cell activity in either mechanism remains controversial. In this study mice that either fully or partially lacked NMDARs in dopamine neurons exclusively, as well as appropriate controls, were evaluated for reward-related learning; this experimental design allowed for a test of the premise th