Repressed PKC delta activation in glycodelin-expressing cells mediates resistance to phorbol ester and TGF beta

Glycodelin is a glycoprotein mainly expressed in well-differentiated epithelial cells in reproductive tissues. In normal secretory endometrium, the expression of glycodelin is abundant and regulated by progesterone. In hormone-related cancers glycodelin expression is associated with well-differentiated tumors. We have previously found that glycodelin drives epithelial differentiation of HEC-1B endometrial adenocarcinoma cells, resulting in reduced tumor growth in a preclinical mouse model. Here we show that glycodelin-transfected HEC-1B cells have repressed protein kinase C delta (PKC delta) activation, likely due to downregulation of PDKI, and are resistant to phenotypic change and enhanced migration induced by phorbo112-myristate 13-acetate (PMA). In control cells, which do not express glycodelin, the effects of PMA were abolished by using PKC6 and PDKI inhibitors, and knockdown of PKC delta, MEK1 and 2, or ERK1 and 2 by siRNAs. Similarly, transforming growth factor beta (TGF beta)-induced phenotypic change was only seen in control cells, not in glycodelin-producing cells, and it was mediated by PKC delta. Taken together, these results strongly suggest that PKC delta, via MAPI( pathway, is involved in the glycodelin-driven cell differentiation rendering the cells resistant to stimulation by PMA and TGF beta. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Use of simultaneously available enrichments by farmed blue fox (Alopex lagopus)

V2009o

KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

In this focused review, we address the role of the kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), in the regulation of angiogenesis. Early studies suggest that KLK3 is able to inhibit angiogenic processes, which is most likely dependent on its proteolytic activity. However, more recent evidence suggests that KLK3 may also have an opposite role, mediated by the ability of KLK3 to activate the (lymph)angiogenic vascular endothelial growth factors VEGF-C and VEGF-D, further discussed in the review

KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

In this focused review, we address the role of the kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), in the regulation of angiogenesis. Early studies suggest that KLK3 is able to inhibit angiogenic processes, which is most likely dependent on its proteolytic activity. However, more recent evidence suggests that KLK3 may also have an opposite role, mediated by the ability of KLK3 to activate the (lymph)angiogenic vascular endothelial growth factors VEGF-C and VEGF-D, further discussed in the review

KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

In this focused review, we address the role of the kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), in the regulation of angiogenesis. Early studies suggest that KLK3 is able to inhibit angiogenic processes, which is most likely dependent on its proteolytic activity. However, more recent evidence suggests that KLK3 may also have an opposite role, mediated by the ability of KLK3 to activate the (lymph)angiogenic vascular endothelial growth factors VEGF-C and VEGF-D, further discussed in the review.Peer reviewe

Käytäntöön pohjautuvia näkemyksiä esitutkintayhteistyön tilasta, kipukohdista ja alueellisista innovaatioista : Tilannekatsaus 2021

Oikeusministeriö on 30.11.2020 tehdyllä toimeksiantosopimuksella (VN/19958/2020) sopinut Syyttäjälaitoksen kanssa käynnistettävästä esitutkintayhteistyön toimivuutta selvittävästä tutkimushankkeesta. Hanke toteutettiin tiiviissä yhteistyössä poliisihallituksen kanssa. Tutkimushankkeeseen nimettiin erikoissyyttäjä Hannu Koistinen Pohjois-Suomen syyttäjäalueelta ja rikoskomisario Eveliina Karjalainen Oulun poliisilaitokselta. Hankkeen kuulemisissa pyrittiin huomioimaan kaikki rikosprosessiketjun toimijat. Tutkimushankkeessa tuli toteutussuunnitelman mukaisesti arvioida esitutkintayhteistyövelvoitteen noudattamista ja tarkastella kehittämismahdollisuuksia esitutkintaviranomaisten ja syyttäjien toiminnassa. Tavoitteena oli saada tietoa esitutkintayhteistyön toimivuudesta eri rikoslajeissa; vaativissa rikosasioissa, tavanomaisissa rikosasioissa ja nopeasti käsiteltävissä rikosasioissa käsittäen myös esitutkinnan rajoittamisasiat sekä kansainvälisliityntäisissä asioissa. Huomioon tuli ottaa rikosasiassa tehtävät esitutkintatoimenpiteet ja arvioida esitutkintayhteistyötä niiden kannalta. Erityisesti tuli arvioida, miten syyttäjän juridista ja strategista asiantuntemusta voitaisiin hyödyntää enemmän esitutkintavaiheessa. Esitutkintaprosessista tuli erityisesti tarkastella erityisesti tutkintasuunnitelman ja loppulausuntomenettelyn käyttöä ja toimivuutta sekä syyttäjän osallistumista niihin sekä avustajien aktiivisempaa roolia. Valtakunnallisia eroja ja poikkeavuuksia tuli selvittää sekä kerätä parhaita käytäntöjä eri alueilta. Hankkeessa tuli kuulla poliisin ja muiden esitutkintaviranomaisten, Syyttäjälaitoksen, tuomioistuinten ja asianajajien edustajia. Loppuraportissa tuli esittää hankkeessa tehdyt havainnot ja johtopäätökset esitutkintayhteistyön toimivuudesta sekä arvio havaituista ongelmista ja esittää ratkaisuehdotuksia niihin. Eri alueilla havaittuja hyviä käytäntöjä tuli esittää monistettavaksi valtakunnallisesti sovellettavaksi. Lisäksi havaittuja tarpeellisia muutostarpeita yhteistyökäytäntöihin, Syyttäjälaitoksen ja Poliisihallituksen ohjeistukseen ja lainsäädäntöön tuli tuoda perustellusti esiin. Tutkimushankkeen raportti on toimitettu oikeusministeriöön 10.5.2021

Alarm system for insect migration using weather radars

The pilot system for forecasting insect migrations to next two days will be operated during May and June 2008. Forecasts are concentrating on two major pests; namely diamond-back moth and bird cherry aphid. Five to ten pilot users will get automatic SMS warning messages and are able to study the situation more thoroughly via specific web pages. The pilot users report to the study team about their findings and the usefulness of the service. The validity of the service will be tested using field traps

Immunoassay for trypsinogen-4

Trypsin has been identified as a pancreatic protease comprising three isoenzymes, trypsin-1,-2, and-3. However, the gene for trypsinogen-3, PRSS3, also gives rise to additional variants, trypsinogen-4A and B, which differ from trypsinogen-3 only with respect to the leader-peptide part, and when activated are identical to trypsin-3. The unique overlapping leader peptides of trypsinogen-4A and B allowed us to develop a specific sandwich-type immunofluorometric assay that detects both these isoforms, but not trypsinogen-3 or activated trypsinogen-4. We measured the concentrations of trypsinogen-4 in various cell line lysates and bile of primary sclerosing cholangitis patients. Lysates of cell lines MDA-MB-231 and PC-3, and astrocytes contained trypsinogen-4, while the conditioned media from these cells did not, suggesting that trypsinogen-4, lacking a classical signal sequence, is not secreted from the cells. Interestingly, 5.7% of the 212 bile samples analyzed contained measurable (>2.4 mu g/l) trypsinogen-4. In conclusion, we have established a specific assay for trypsinogen-4 and demonstrated that trypsinogen-4 can be found in biological samples. However, the clinical utility of the assay remains to be established.Peer reviewe

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p < 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p < 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia