Different expression of cyclooxygenase-2 (COX-2) in selected nonmelanocytic human cutaneous lesions

The aim of our study was to elucidate the possible involvement of COX-2 in the development and/or progression of nonmelanocytic skin lesions. To evaluate the usefulness of that enzyme as a potential molecular marker, we examined the intensity and spatial distribution of COX-2 expression in selected types of such tumors using the same immunohistochemical procedure as in our earlier studies of melanocytic cancers. We examined 20 benign epithelial lesions, 11 precancerous lesions, 21 basal cell carcinomas (BCC), 14 squamous cell carcinomas (SCC) and eight fibromas. The levels of COX-2 expression detected in benign lesions and in normal skin were comparable. Elevated expression of this protein may play a role in the development of SCC, as indicated by strong immunostaining both in SCCs and precancerous lesions. Significantly stronger staining in SCCs compared to BCCs may indicate a role of COX-2 in cancer malignancy and serve as an indicator useful for differential diagnostics of the two types of cancer. Strong staining in all skin layers of SCC may help in detecting cancer cells infiltrating surrounding skin layers. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 381–388

Podejrzenie nowotworu pęcherzykowego czy nowotwór pęcherzykowy? Dylemat patologa i chirurga

  Introduction: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term “Suspicious for Follicular Neoplasm” (SFN) in cytological diagnostics of thyroid carcinoma. Material and methods: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. Results: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. Conclusions: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis. (Endokrynol Pol 2016; 67 (1): 17–22)    Wstęp: Materiał cytologiczny biopsji aspiracyjnej cienkoigłowej (BAC) tarczycy nie pozwala na zróżnicowanie raków pęcherzykowych, gruczolaków i guzków rozrostowych. Ograniczeniem metody jest brak możliwości określenia obecności torebki guza, jej ewentualnego nacieku oraz angioinwazji. Jednoznaczne rozstrzygnięcie czy mamy do czynienia ze zmianą nowotworową czy łagodną jest możliwe dopiero po badaniu histopatologicznym. Celem pracy było uzasadnienie celowości używania terminu „podejrzenie nowotworu pęcherzykowego” w diagnostyce cytologicznej raka tarczycy. Materiał i metody: Poddano analizie 352 wyniki BAC tarczycy wykonanych w Instytucie Onkologii (IO) w Gliwicach w latach 2010–2015 i ich korelację z rozpoznaniem histopatologicznym. Wyniki: W IO rozpoznanie podejrzenie nowotworu pęcherzykowego (grupa IV wg Systemu Bethesda) postawiono pierwotnie w 352 przypadkach. Leczenie operacyjne podjęto po pierwszej BAC w 6 przypadkach uzyskując potwierdzenie nowotworu w 5 przypadkach w tym jednego raka pęcherzykowego. Powtórna BAC przeprowadzona u 90 pacjentów potwierdziła rozpoznanie grupy IV w 53 przypadkach. Trzecią BAC przeprowadzono u 26 chorych, uzyskując kolejnych 14 rozpoznań grupy IV. Leczeniu operacyjnemu poddano 26 pacjentów na 352 rozpoznania nowotworu pęcherzykowego, uzyskując potwierdzenie nowotworu w 19 przypadkach, co stanowi 73% w tym raka 5 razy. Wnioski: Wysoka dodatnia wartość predykcyjna PPV = 73% rozpoznania „podejrzenie nowotworu pęcherzykowego” uzasadnia podjęcie leczenia operacyjnego w każdym przypadku tego rozpoznania. (Endokrynol Pol 2016; 67 (1): 17–22)

Kliniczne znaczenie rozpoznania zmiany pęcherzykowej bliżej nieokreślonej (grupa III wg Systemu Bethesda) w biopsji aspiracyjnej cienkoigłowej (BAC)

  Introduction: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). Material and methods: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. Results: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of “Papillary Thyroid Carcinoma” and one “Suspicious for Papillary Thyroid Carcinoma”. From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was “Suspicious for Malignancy”. In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. Conclusions: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment. (Endokrynol Pol 2016; 67 (1): 12–16)    Wstęp: Zmiana pęcherzykowa bliżej nieokreślona (grupa III) należy do najbardziej kontrowersyjnej kategorii systemu Bethesda. Brak jest polskich opracowań określających stopień ryzyka wystąpienia nowotworu złośliwego po rozpoznaniu zmiany z grupy III. Celem pracy było określenie ryzyka złośliwości po rozpoznaniu zmiany pęcherzykowej bliżej nieokreślonej w materiale Centrum Onkologii w Gliwicach. Materiał i metody: Analizie poddano 395 rozpoznań z grupy III BAC tarczycy wykonanych w latach 2010–2015. Oceniono zgodność pierwotnego rozpoznania grupy III z rozpoznaniami z kolejnych BAC i wynikami badań histopatologicznych. Wyniki: Na 395 rozpoznań grupy III zoperowano ze wskazań klinicznych 27 pacjentów i rozpoznano 6 raków. Ponowną BAC wykonano w 180 przypadkach i pierwotne rozpoznanie potwierdzono w 41 przypadkach. Po drugiej BAC 2-krotnie rozpoznano raka brodawkowatego lub jego podejrzenie. U 8 operowanych w tej serii potwierdzono wcześniejsze cytologiczne rozpoznanie raka u 2. Trzecią i kolejne BAC wykonano u 46 pacjentów i w jednym przypadku podejrzewano raka. Ryzyko raka w zmianie pęcherzykowej bliżej nieokreślonej w analizowanym materiale wynosi 2,78%. Uwzględniając wszystkie powtórnie wykonane 56 BAC, w których potwierdzono pierwotne rozpoznanie grupy III, ryzyko maleje do 2,43%. Wnioski: Rozpoznanie zmiany pęcherzykowej bliżej nieokreślonej przy braku wskazań klinicznych nie jest podstawą do wszczęcia postępowania chirurgicznego. (Endokrynol Pol 2016; 67 (1): 12–16)

Mast cells and their role in pathogenesis of selected skin diseases

Mastocyty, powstające w komórkach hematopoetycznych szpiku kostnego, uwalniają wiele substancji biologicznie czynnych (cytokiny, chemokiny, czynniki wzrostu, neuropeptydy oraz enzymy proteolityczne). Na powierzchni mastocytów znajduje się wiele receptorów determinujących ich funkcje oraz umożliwiających ich interakcje z komórkami układu immunologicznego i neuroendokrynnego skóry. W mastocytozie dochodzi do klonalnej proliferacji MCs, które gromadzą się w tkankach, przede wszystkim w skórze i w szpiku kostnym. W ciężkich postaciach układowych choroby nacieczenie narządów prowadzi do upośledzenia ich funkcji. U chorych zarówno na skórną, jak i układową postać mastocytozy dochodzi do rozwoju objawów zależnych od mediatorów uwalnianych przez mastocyty w procesie degranulacji. W atopowym zapaleniu skóry MCs biorą udział w reakcji nadwrażliwości typu I, promują różnicowanie się limfocytów w kierunku Th2 lub Th1, wydzielają mediatory biorące udział w patogenezie świądu, pobudzają chemotaksję limfocytów i komórek dendrytycznych do skóry oraz przyczyniają się do rozwoju przewlekłego stanu zapalnego skóry. W łuszczycy w obrębie zmian skórnych obserwuje się zwiększoną liczbę MCs, które wydzielają cytokiny prozapalne, stymulują migrację neutrofilów, monocytów i limfocytów do skóry oraz wydzielają mediatory indukujące świąd.Mast cells derived from bone marrow hematopoetic stem cells, have the ability to release multiple biologically active substances (such as cytokines, chemokines, growth factors, neuropeptides, and proteolytic enzymes). On the surface of mast cells, there are numerous receptors that determine the function of these cells and enable them to interact with the cells of the immune system and the neuroendocrine system of the skin. In mastocytosis, there is a clonal proliferation of mast cells which accumulate in various tissues, particularly in the skin and the bone marrow. In severe forms of systemic disease infiltration of organs leads to an impairment of their function. Both patients with cutaneous and systemic mastocytosis suffer from mast cell mediator-related symptoms. In atopic dermatitis MCs are involved in type I hypersensitivity reactions, promote the differentiation of cells towards Th2 or Th1, secrete mediators involved in the pathogenesis of pruritus, stimulate chemotaxis of lymphocytes and dendritic cells into the skin and contribute to the development of chronic inflammation of the skin. In psoriasis an increased number of MCs was found in skin lesions. Moreover, these cells secrete numerous proinflammatory cytokines, stimulate migration of neutrophils, monocytes and lymphocytes into the skin and secrete mediators which induce itching

Argumentationsanalyse von Kommentaren in einem Forum der BBC zur Unabhängigkeit des Kosovo

Die vorliegende Arbeit geht hervor aus dem Hauptseminar „Argumentationstheorie“, das im Wintersemester 2008/09 am Institut für Linguistik der Universität zu Köln unter der Leitung von PD Dr. Leila Behrens abgehalten wurde. Ziel dieses Seminars war es, ausgehend von traditionellen Begriffen der Rhetorik, Dialektik und Logik, in die Terminologie sowie in zentrale Modelle der zeitgenössischen Argumentationsforschung einzuführen. Die dabei erworbenen Kenntnisse sollen im Folgenden bei der Analyse von Beiträgen eines Diskussionsforums im Internet angewendet werden. Hierbei handelt es sich um ein sogenanntes „newsforum“ der BBC mit dem Titel „Have Your Say“ (BBC 2008), in dem aktuelle Themen und Nachrichten von Internetnutzern weltweit diskutiert werden können. Im untersuchten Fall behandeln wir die Frage, wie mit der Unabhängigkeitserklärung des Kosovo vom 17. Februar 2008 umzugehen sei: „Should the world recognise an independent Kosovo?“ […]. Zu dieser Fragestellung wurden insgesamt 3195 Beiträge im Forum veröffentlicht, von denen hier 780 ausgewertet werden. Diese folgen chronologisch aufeinander und umfassen den Zeitraum zwischen 7:49 Uhr (mittlere Greenwich-Zeit) und 14:26 Uhr des 17. Februar 2008

Twelve-Month Evaluation of Temperature Effects of Radiotherapy in Patients after Mastectomy

The aim of this study was to verify the changes in the temperature distribution within the breast at twelve months after the end of radiotherapy for breast cancer. The study included twentyfour women. The first test group consisted of twelve women who underwent breast mastectomy and qualified for radiotherapy according to standard medical treatment procedures. The second group included twelve healthy women. The tests were conducted before treatment with radiation therapy and two months, six months, nine months, and one year after the end of treatment. The mean temperature values changed depending on the time that had elapsed since the end of treatment. The highest temperature increase in all patients was observed six months after the end of radiotherapy. This research has confirmed that the assessment of temperature changes in the breast area after radiotherapy can evaluate the severity and lesions in the time course of the radiation reaction

Correlation between isotherms and isodoses in breast cancer radiotherapy - first study

The study is focused on correlation of isotherms derived from thermal images with an isodoses describing treatment plan for patients with breast cancer treated by radiotherapy. The irradiated area covered the part of the body after mastectomy. The study included patients diagnosed with breast cancer who were qualified for radiotherapy treatment. All patients were monitored during each treatment week during the entire radiotherapy process. The measurements were made under strictly defined conditions. In the treatment planning system (TPS), the specific plan was created for each patient. Spatial dose distribution in the patient’s body was obtained and presented by the isodoses (lines connecting points with the same dose values). The following areas from the treatment planning system were plotted on the thermograms: target (tumor area) and isodose: 45 Gy, 40 Gy, 30 Gy, 20 Gy and 10 Gy. The obtained results indicated a high correlation between magnitude of the dose represented as the isodose and the temperature of the treated skin. Moreover, preliminary analysis showed a repeatable increase of the mean temperature in the irradiated area during the treatment

The Chemogenetic Receptor Ligand Clozapine N-Oxide Induces<em> in vivo</em> Neuroreceptor Occupancy and Reduces Striatal Glutamate Levels

Chemogenetic studies with the ligand clozapine N-oxide (CNO) are predicated upon the assumption that CNO is devoid of actions at natural neuroreceptors. However, recent evidence shows that CNO may be converted back to clozapine (CLZ) in vivo, which could yield plasma concentrations that may be sufficient to occupy inter alia dopamine D2=3 and serotonin 5HT2A receptors in living brain. To test this phenomenon, we measured striatal dopamine D2=3 receptor occupancy with [18F]fallypride PET and serotonin 5HT2A occupancy ex vivo using [18F]MH.MZ. We found a CNO dosedependent effect on the availability of both neuroreceptor sites. In parallel MR spectroscopy experiments, we found that CNO reduced creatine C phosphcreatine (CrCPCr) and increased N-acetylaspartate C N-acetylaspartylglutamate (NAACNAAG) signals in the prefrontal cortex, and also reduced the glutamate signal in dorsal striatum, with peak effect at 2 mg/kg. Thus, our findings suggest that conversion of CNO to CLZ in living rats imparts significant occupancy at endogenous neuroreceptors and significant changes to neurometabolite levels

Long-term sustainability of a distributed RI: the EPOS case

The European Plate Observing System (EPOS) is a distributed research infrastructure (RI) with the mission to establish and maintain sustainable and long-term access to solid Earth science data and services by integrating the diverse national research infrastructures under a common federated framework governed by EPOS ERIC (European Research Infrastructure Consortium). This paper presents the EPOS approach to ensure financial viability and to tackle the challenge of long-term sustainability of the RI during its operational phase. The EPOS approach to sustainable operation considers the scientific impact and the promotion of scientific research as the preconditions to achieve long-term sustainability. Enabling scientific excellence implies that high-quality data and services are provided reliably and continuously to establish the RI as the enabler of investigations to solid Earth scientists. The strategic approach and the solutions adopted by EPOS ERIC to address the long-term sustainability of a pan-European distributed RI are discussed in this paper focusing on the governance structure, considered as the qualifying dimension that gathers and connects the financial, legal and technical dimensions. The governance and the financial models are discussed to delineate the legal framework necessary to operate the EPOS RI relying on the implemented technical solutions. A sufficiently stable investment environment is necessary to allow the RI to concentrate on providing high quality services for their user communities. This paper discusses the current actions and challenges to be addressed for achieving this goal.publishedVersio

Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion

Funding Information No funding information provided. aThese authors contributed equally to this work