Thyroid Hormone Deiodinases and Cancer

Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches

Using a GIS technology to plan an agroforestry sustainable system in Sardinia

This study was conducted with the aim to quantify the spread of livestock agroforestry in a Mediterranean ecosystem (island of Sardinia, Italy) and evaluate its sustainability in terms of grazing impact. By using GIS software ArcMap 10.2.2, the map of Sardinia vegetal landscape, obtained by information of Sardinia nature map based on the classification of habitat according to CORINE-Biotopes system, have been overplayed with the map of livestock grazing impact map CAIA developed by INTREGA (spin-off ENEA), to obtain for Meriagos (local agro-silvo-pastoral systems; classified “Dehesa 84.6” according to CORINE-Biotopes system), bushlands and woodlands, the surfaces under grazing and evaluate the extension of overgrazing for each of them

Osservazioni istochimiche e immunoistochimiche sull'ipofisi anteriore di un cane affetto da malattia di Cushing

Gli adenomi del lobo anteriore dell'ipofisi sono neoplasie benigne piuttosto frequenti. Essi mostrano aspetto circoscritto e accrescimento non invasivo nei confronti dei tessuti circostanti. Il tumore a cellule secernenti ACTH, che colpisce le cellule cromofobe della pars anteriore dell'ipofisi, è uno di questi e viene associato alla sindrome di Cushing, causando evidente ipercortisolemia per stimolazione della corteccia surrenale. Un cane meticcio, femmina, di 7 anni, in terapia per sospetta Sindrome di Cushing e pervenuto a morte, è stato sottoposto ad accurato esame necroscopico, durante il quale si procedeva tra l'altro a prelevare ghiandole surrenali, polmone, fegato, cute, muscoli e intera ghiandola pituitaria. Su detti organi veniva eseguito l'esame istopatologico per la ricerca delle lesioni tipiche determinate dalla sindrome. Sulla ghiandola pituitaria, aumentata notevolmente di volume, venivano eseguite indagini istopatologiche specifiche, mediante colorazione OFG, per differenziare gli istotipi costituenti la pars anteriore. Tale colorazione ha consentito di riscontrare e identificare tra le cellule pituitarie gli elementi acidofili, basofili e cromofobi; queste ultime cellule, aumentate di numero, erano d'aspetto omogeneo e formavano un nucleo compatto e con scarso stroma al centro della ghiandola. La caratterizzazione cromatica e la differenziazione dai restanti istotipi ha reso possibile identificare la neoplasia come adenoma ipofisario di tipo "diffuso", caratterizzato per l'appunto da cellule disposte a strati, con scarso stroma e debole vascolarizzazione. Per verificare l'ormonoattività  delle cellule neoplastiche si è proceduto all'esame immunoistochimico per la ricerca dell'ACTH. Il risultato di tale indagine ha dato esito positivo, confermando l'intensa attività secernente delle cellule oggetto di studio

hMAF, a Small Human Transcription Factor That Heterodimerizes Specifically with Nrf1 and Nrf2

A 1.6-kilobase pair full-length cDNA encoding a transcription factor homologous to the Maf family of proteins was isolated by screening a K562 cDNA library with the NFE2 tandem repeat probe derived from the globin locus control region. The protein, which was designated hMAF, contains a basic DNA binding domain and an extended leucine zipper but lacks any recognizable activation domain. Expressed in vitro, the hMAF protein is able to homodimerize in solution and band-shift the NFE2 tandem repeat probe. In addition to homodimers, hMAF can also form high affinity heterodimers with two members of the NFE2/CNC-bZip family (Nrf1 and Nrf2) but not with a third family member, p45-NFE2. Although hMAF/hMAF homodimers and hMAF/Nrf1 and hMAF/Nrf2 heterodimers bind to the same NFE2 site, they exert functionally opposite effects on the activity of a linked gamma-globin gene. In fact, whereas all hMAF/CNC-bZip heterodimers stimulate the activity of a gamma-promoter reporter construct in K562 cells, the association into homodimers that is induced by overexpressing hMAF inhibits the activity of the same construct. Thus variations in the expression of hMAF may account for the modulation in the activity of the genes that bear NFE2 recognition sites

PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

This is an Open Access article under the terms of the Creative Commons Attribution License.Camptothecin (CPT; (S)-(+)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione) is a highly cytotoxic natural alkaloid that has not yet found use as chemotherapeutic agent due to its poor water-solubility and chemical instability and, as a consequence, no effective administration means have been designed. In this work, camptothecin has been successfully loaded into iron oxide superparamagnetic nanoparticles with an average size of 14 nm. It was found that surface modification of the nanoparticles by polyethylene glycol enables loading a large amount of camptothecin. While the unloaded nanoparticles do not induce apoptosis in the H460 lung cancer cell line, the camptothecin-loaded nanoparticle formulations exhibit remarkable proapoptotic activity. These results indicate that camptothecin retains its biological activity after loading onto the magnetic nanoparticles. The proposed materials represent novel materials based on naturally occurring bioactive molecules loaded onto nanoparticles to be used as chemotherapeutic formulations. The procedure seems apt to be extended to other active molecules extracted from natural products. In addition, these materials offer the potential of being further implemented for combined imaging and therapeutics, as magnetic nanoparticles are known to be multifunctional tools for biomedicine.This work was supported by Fundación Progreso y Salud, Consejería de Salud (PI0070) and Proyecto de Investigación de Excelencia de la Junta de Andalucía (P10-FQM-6615).Peer Reviewe

Histopathological, histochemical and immunoistochemical study on a rare case of granulocytic sarcoma in a dog

Granulocytic sarcoma is a malignant extramedullary solid tumor, composed of granulocytic precursor cells at various levels of differentiation. Three differentiation levels are considered: blastic, immature, and differentiated, and cases with unusual morphology. Nowadays the aid of more and more highly developed techniques allows to differentiate the various histotypes. We report a case of a 5 year-old female Schnautzer dog, died after a serious dyspnoea. During the autopsy the veterinary found several neoplasias in the lungs. It has been found a very large white-greyish mediastinal neoplasia, stuck at the trachea and several more in the parenchyma. Several samples were fixed in formalin, embedded in paraffin and exposed to histochemistry staining (H.E., Giemsa), cytochemistry (Naphthol-AS-D-Chloroacetate), and immunohistochemistry (anti-CD3, -CD79a, -CD45, -MPO, -CD45Ro, -CD34, -CD20, -CD68, -CD15, -CD30, -CD117, -CD235a, -Factor VIII, -elastase and anti-Pan-cytocheratine). Neoplasia, poorly circumscribed, was composed by a large number of neutrophil granulocytes with different degrees of differentiation, including elements of myeloid lineage. Cells were positive to MPO and focal to Naphtol-As-D-Chloroacetate and were negative to all the others antisera, allowing us to exclude lymphomas, small cells carcinomas, and tumors of monocytic and erythroid origin. By these characteristics we could diagnose a rare case of neutrophilic granulocytic sarcoma, of immature type progressing to mature form

Direct oral Xa inhibitors versus warfarin in patients with cancer and atrial fibrillation: a meta-analysis

Patients with cancer are at higher risk of atrial fibrillation, thromboembolic complications and bleeding events compared with the general population. The aim of the present meta-analysis was to compare the efficacy and safety of direct oral Xa inhibitor anticoagulants versus warfarin in patients with cancer and atrial fibrillation

Towards a new national cork plan for Italy, between critical issues and new challenges

Conservation of the unique cork oak habitat (both as sparse forest with a well-developed shrub and herbaceous layer, and as semi-natural systems maintainedby livestock breeding), sustainable cork utilization, solid ties with the wine industry, appropriate legislation oriented towards rural development and research into innovative cork products are some of the main key-points discussed recently in the framework of the National Cork Plan update. We emphasize here the most relevant topics, which have emerged in the discussion between representatives of research institutions and cork oak stakeholders, coordinated by the Ministry of Agricultural, Food and Forestry Policies

Veterinarski obilazak mliječnih farmi s povećanim brojem somatskih stanica i bakterija iznad zakonom dozvoljenih vrijednosti

The EU Directives 92/46 and 92/47 (D.P.R. 54/97 under national legislation) fix the agreed levels of somatic cell counts and total bacterial counts allowed in milk. Over a one year period, a total of 165farms which did not comply with one or more such legal requirements were visited and monitored. This was in order to check and, where necessary, correct the hygienic and sanitary management of the farm. A comparison of the bulk tank milk somatic cell count (BTMSCC) before and after the veterinary visit, shows improvements in all the farms which were tested. In a relatively short time, visited dairy farms with a somatic cell content between 401.000 and 500.000 cells/ml managed to comply with the parameters set down by law, achieving a mean of 304.000 cells/ml. However, those farms with a somatic cell counts between 501.000 and 800.000 cells/ml required further technical action. In fact, despite considerable improvements (mean somatic cell count decreasing from 638.000 cells/ml to 403.000 cells/ml), it was not possible to meet the required levels so rapidly. On these farms, a second veterinary visit was needed as well as more specific milk sampling for bacteriological assay and therapeutic guidelines in order to meet the specified requirements.Smjernicama 92/46. i 92/47. (D.P.R. 54/97). Europska unija je utvrdila maksimalno dozvoljene vrijednosti ukupnog broja bakterija i somatskih stanica u mlijeku. Unutar godine dana posjećeno je 165 farmi koje nisu zadovoljavale svim uvjetima. Posjet je obavljen s ciljem da se snimi postojeća situacija, i, ukoliko je neophodno, da se provedu adekvatne korekcije u higijenskom i sanitarnom vođenju farmi. Usporedbom broja somatskih stanica (BTMSCC) u dobavnim tankovima za mlijeko, prije i poslije veterinarske posjete, uočena su poboljšanja na svim ispitanim farmama. Ispitane mliječne farme s brojem somatskih stanica između 401000 i 500.000 stanica/mL u relativno kratkom vremenu uspjele su smanjiti taj broj na prosječnih 304.000 stanica/mL, što udovoljava propisanim vrijednostima. Međutim, na farmama s brojem somatskih stanica između 501.000 i 800.000 Stanica/mL potrebno je provesti dodatne tehničke mjere. Usprkos značajnom poboljšanju (prosječni broj somatskih stanica smanjene je sa 638.000 stanica/mL na 403.000 stanica/mL), nisu dobivene vrijednosti unutar zakonski propisanih. Ovim farmama bio je potreban dodatni veterinarski posjet kao i specifično bakteriološko ispitivanje te terapeutski naputci s ciljem da se postigne usuglašenost sa specifičnim zahtjevima