FAM3B/PANDER, é uma nova proteína tipo citocina pertencente a família FAM3. Foram reveladas algumas similaridades estruturais entre o FAM3B e outras citocinas associadas ao câncer, como IL-6 e FAM3C suportando a hipótese, de que FAM3B também poderia estar envolvido na progressão tumoral. Considerando que o FAM3B é expresso por tumores de mama, este trabalho dedicou-se a elucidar suas possíveis funções em tumores, a partir de um modelo de superexpressão na linhagem celular tumoral da mama, MDA-MB-231. Ensaios celulares e moleculares sugeriram que o FAM3B é capaz de conferir, proteção à morte celular e de aumentar taxa de migração nas células MDA-MB-231 via, principalmente, Bcl-2 e Bcl-xL. Em concordância, os resultados in vivo demonstraram aumento do volume e peso tumoral, com aumento da expressão de Bcl-2 nos tumores dos animais inoculados com as células MDA-MB-231-FAM3B. Estes resultados indicam que esta proteína, exerce funções nas etapas de invasão e metástase em tumores de mama, o que permite considerar o FAM3B, como um possível candidato a marcador tumoral. / FAM3B/PANDER is a new cytokine-like protein, member of the new FAM3 family. Recent data has been shown similarities between FAM3B/PANDER and others citokines involved in tumor progression, like IL-6 and FAM3C/ILEI, supporting the hypothesis that FAM3B is also involved in tumor progression. In Silico data revealed that FAM3B is expressed by breast tumors and using the overexpression of FAM3B in MDA-MB-231 tumor cell line, the aim was evaluated possible roles of FAM3B in breast tumor progression. The results revealed that FAM3B overexpression inhibits cell death and promotes cell migration in MDA-MB-231 cell line, through, at least in parts, Bcl-2 and Bcl-xL pathways. In agreement, in vivo results shown an increase in volume, weight tumors and increase expression of Bcl-2 in mice with cells overexpressing FAM3B.These results suggest important functions of this protein in cell invasiveness and migration, which allows us to consider, FAM3B as a possible future candidate as a molecular biomarker.

PANDER/FAM3B (PANcreatic-DERived factor) é uma citocina capaz de induzir apoptose em células-β secretoras de insulina e regular a homeostase da glicose nos tecidos periféricos. Considerando que PANDER/FAM3B também é expresso em tumores de próstata, o presente trabalho avaliou o papel desta citocina na inibição da apoptose in vitro, assim como o crescimento e invasividade tumoral de células de carcinoma de próstata da linhagem DU145 in vivo, usando o modelo de superexpressão estável mediada por lentivirus. Os nossos resultados apontam um aumento da viabilidade e uma diminuição da morte celular em células que superexpressam PANDER quando comparadas ao grupo controle. Este efeito protetor é acompanhado por um aumento da expressão de genes anti-apoptoticos e uma diminuição da atividade proteolítica das caspases. Por outro lado, a superexpressão de PANDER/FAM3B por tumores in vivo se correlaciona com aumento da massa tumoral e o aumento de vasos sanguíneos nos tumores. Em síntese, nossos dados demonstram que, em contraste ao papel observado em células β-pancreáticas, o PANDER/FAM3B inibe morte celular e promove a tumorigenicidade e o crescimento tumoral in vivo, sugerindo ao mesmo tempo, algum envolvimento com angiogênese e metástase em células DU145. / PANDER / FAM3B (pancreatic-derived factor) is a cytokine capable of inducing apoptosis in secreting β-cells and insulin to regulate glucose homeostasis in peripheral tissues. Whereas PANDER / FAM3B is also expressed in prostate tumors, this study evaluated the role of this cytokine in the inhibition of apoptosis in vitro as well as tumor growth and invasiveness of prostate carcinoma DU145 cells lineage in vivo, using the model Stable overexpression mediated by lentivirus. Our results suggest that increased viability and decreased cell death in cells that overexpress PANDER when compared to the control group. This protective effect is accompanied by an increased expression of anti-apoptotic genes and a decrease in proteolytic activity of caspases. Moreover, overexpression of PANDER / FAM3B by tumors in vivo correlates with increased tumor mass and the increase of blood vessels in tumors. In summary, our data demonstrate that in contrast to the role observed in pancreatic cells, PANDER / FAM3B inhibits cell death and promotes tumorigenicity and tumor growth in vivo, suggesting at the same time, some involvement in angiogenesis and metastasis in cell DU145.

PANDER/FAM3B (PANcreatic-DERived factor) é uma citocina capaz de induzir apoptose em células-β secretoras de insulina e regular a homeostase da glicose nos tecidos periféricos. Considerando que PANDER/FAM3B também é expresso em tumores de próstata, o presente trabalho avaliou o papel desta citocina na inibição da apoptose in vitro, assim como o crescimento e invasividade tumoral de células de carcinoma de próstata da linhagem DU145 in vivo, usando o modelo de superexpressão estável mediada por lentivirus. Os nossos resultados apontam um aumento da viabilidade e uma diminuição da morte celular em células que superexpressam PANDER quando comparadas ao grupo controle. Este efeito protetor é acompanhado por um aumento da expressão de genes anti-apoptoticos e uma diminuição da atividade proteolítica das caspases. Por outro lado, a superexpressão de PANDER/FAM3B por tumores in vivo se correlaciona com aumento da massa tumoral e o aumento de vasos sanguíneos nos tumores. Em síntese, nossos dados demonstram que, em contraste ao papel observado em células β-pancreáticas, o PANDER/FAM3B inibe morte celular e promove a tumorigenicidade e o crescimento tumoral in vivo, sugerindo ao mesmo tempo, algum envolvimento com angiogênese e metástase em células DU145. / PANDER / FAM3B (pancreatic-derived factor) is a cytokine capable of inducing apoptosis in secreting β-cells and insulin to regulate glucose homeostasis in peripheral tissues. Whereas PANDER / FAM3B is also expressed in prostate tumors, this study evaluated the role of this cytokine in the inhibition of apoptosis in vitro as well as tumor growth and invasiveness of prostate carcinoma DU145 cells lineage in vivo, using the model Stable overexpression mediated by lentivirus. Our results suggest that increased viability and decreased cell death in cells that overexpress PANDER when compared to the control group. This protective effect is accompanied by an increased expression of anti-apoptotic genes and a decrease in proteolytic activity of caspases. Moreover, overexpression of PANDER / FAM3B by tumors in vivo correlates with increased tumor mass and the increase of blood vessels in tumors. In summary, our data demonstrate that in contrast to the role observed in pancreatic cells, PANDER / FAM3B inhibits cell death and promotes tumorigenicity and tumor growth in vivo, suggesting at the same time, some involvement in angiogenesis and metastasis in cell DU145.

FAM3B/PANDER, é uma nova proteína tipo citocina pertencente a família FAM3. Foram reveladas algumas similaridades estruturais entre o FAM3B e outras citocinas associadas ao câncer, como IL-6 e FAM3C suportando a hipótese, de que FAM3B também poderia estar envolvido na progressão tumoral. Considerando que o FAM3B é expresso por tumores de mama, este trabalho dedicou-se a elucidar suas possíveis funções em tumores, a partir de um modelo de superexpressão na linhagem celular tumoral da mama, MDA-MB-231. Ensaios celulares e moleculares sugeriram que o FAM3B é capaz de conferir, proteção à morte celular e de aumentar taxa de migração nas células MDA-MB-231 via, principalmente, Bcl-2 e Bcl-xL. Em concordância, os resultados in vivo demonstraram aumento do volume e peso tumoral, com aumento da expressão de Bcl-2 nos tumores dos animais inoculados com as células MDA-MB-231-FAM3B. Estes resultados indicam que esta proteína, exerce funções nas etapas de invasão e metástase em tumores de mama, o que permite considerar o FAM3B, como um possível candidato a marcador tumoral. / FAM3B/PANDER is a new cytokine-like protein, member of the new FAM3 family. Recent data has been shown similarities between FAM3B/PANDER and others citokines involved in tumor progression, like IL-6 and FAM3C/ILEI, supporting the hypothesis that FAM3B is also involved in tumor progression. In Silico data revealed that FAM3B is expressed by breast tumors and using the overexpression of FAM3B in MDA-MB-231 tumor cell line, the aim was evaluated possible roles of FAM3B in breast tumor progression. The results revealed that FAM3B overexpression inhibits cell death and promotes cell migration in MDA-MB-231 cell line, through, at least in parts, Bcl-2 and Bcl-xL pathways. In agreement, in vivo results shown an increase in volume, weight tumors and increase expression of Bcl-2 in mice with cells overexpressing FAM3B.These results suggest important functions of this protein in cell invasiveness and migration, which allows us to consider, FAM3B as a possible future candidate as a molecular biomarker.

PANcreatic DERived factor (PANDER, FAM3B) is a member of a superfamily of FAM3 proteins that are uniquely structured and strongly expressed from the endocrine pancreas and co-secreted with insulin. Unique animal models available to our lab have indicated that PANDER can induce a selective hepatic insulin resistant (SHIR) phenotype whereby insulin signaling is blunted yet lipogenesis is increased. The complexity of the biological networks involved with this process warranted the logical approach of employing quantitative mass spectrometry based proteomic analysis using stable isotope labeling of amino acids in cell culture (SILAC) to identify the global proteome differences between the PANDER transgenic (TG) overexpressing murine model to matched wild-type mice under three metabolic states (fasted, fed and insulin stimulated). Additionally, this technique was used to compare the hepatic proteome of mice on a high fat diet to elucidate early and late mechanisms of disease progression. The “spike-in” process was employed by equal addition of lysate obtained from livers of heavy L-Lysine (13C6, 97%) fed mice to the mice liver protein lysate (PANTG and WT) for relative quantitative analysis. Upon acquisition of the dataset by use of liquid chromatography tandem mass spectrometry (LC-MS/MS, LTQ Orbitrap), geometric means and Uniprot Protein identification numbers were uploaded to Ingenuity Pathway Analysis (IPA) to reveal the effect of PANDER on hepatic signaling. IPA identified lipid metabolism and fatty acid synthesis as top cellular functions differentially altered in all metabolic states. Several molecules with a role in lipid metabolism were identified and include FASN, ApoA1, ApoA4, SCD1, CD36, CYP7A1 and ACC. Furthermore, central to the differentially expressed proteins was the revealed activation of the liver X receptor (LXR) pathway. In summary, our SILAC proteomic approach has elucidated numerous previously unidentified PANDER induced molecules and pathways resulting in increased hepatic lipogenesis. In addition, we have demonstrated strong utility of this approach in comprehensively phenotyping animal models of hepatic insulin resistance. PANDER may potentially propagate pro-hepatic lipogenic effects by LXR activation in contrast to increased LXRα expression. This can be evaluated through the use of LXR agonists (T0901317) antagonists (GSK 2033). LXR activity can be measured by luciferase assays using an LXRE response plasmid. Our central hypothesis is that PANDER induces activation of LXR and is measured and predicted in our line of experiments. In general, PANDER induced LXR activation will be enhanced by T0901317 and diminish effects of GSK 2033 along with direct correlation of downstream metabolic effects such as increased hepatic lipogenesis and fatty acid metabolism. Taken together, PANDER strongly impacts hepatic lipid metabolism and may induce a SHIR phenotype via the LXR pathway. Additionally, phosphoproteomic analysis uncovered large-scale differences in protein phosphorylation states as PANDER impacts insulin signaling. A notable finding was the increased phosphorylation of glycogen synthase (GSK), possibly responsible for the decreased hepatic glycogen content in the PANTG mouse. In an effort to map out critical molecules involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis, the same proteomic approach was carried out, providing a unique dataset of differentially expressed hepatic proteins due to a high at diet.

Background Substance use disorder [SUD] is a global problem and opioids is a growing partof the overdoses worldwide. Sweden has a high mortality rate related to narcotics compared tothe rest of the EU. Nurses meet people with SUD when people with SUD are seeking care. People with SUD are usually met with stigma and have a risk of getting worse care in a healthcare setting. Aim The aim with this study is to describe nurses’ experiences of meeting people with SUD. Method This study is a literature study. Seven qualitative articles were analyzed with acontent analysis approach. Results The results show that nurses had a sense of insecurity being present in the meetingwith people with SUD. The presence of insecurity comes from a more demanding care, afeeling of being vigilant, lack of information and that nurses’ integrity is under threat. Conclusions People with SUD are a vulnerable group with a risk of being exposed for carepanding and in many cases nurses experience a kind of insecurity while caring for them. / Bakgrund Beroendeproblematik är ett problem globalt där opiater står för en stor och ökadmängd överdoser. Sverige har en hög dödlighet kopplat till narkotika preparat i jämförelsemed resten av EU. Sjuksköterskor möter personer med beroendeproblematik när de sökervård. Personer med beroende möts av både stigma och riskerar sämre vård inom hälsosjukvården. Syfte Syftet var att beskriva sjuksköterskors upplevelser av att möta personer medberoendeproblematik. Metod Studien är en allmän litteraturstudie. Sju kvalitativa artiklarna inkluderades ochinnehållsanalys valdes med en induktiv ansats. Resultat Resultatet visar på hur en upplevd osäkerhet är närvarande hos sjuksköterskor imötet med personer som har en beroendeproblematik. Upplevelserna innefattar att vården ärkrävande, ett ökat behov att vara vaksam, informationsbrist och att sjuksköterskor integritet ärhotad. Slutsats Personer med beroendeproblematik är en sårbar grupp som riskerar att utsättas förvårdlidande och som sjuksköterskor i flera fall upplever en osäkerhet i att vårda.

Christian Heinrich Pander begründete 1817 in Würzburg die Keimblatttheorie. Zu seinen Erkenntnissen gelangte er durch Studien am Hühnerembryo. Beim Erlernen und bei der Durchführung der wissenschaftlichen Methodik mit dem Mikroskop unterstützte ihn der Würzburger Professor und Naturforscher Ignaz Döllinger maßgeblich. Neben der Aufarbeitung der wissenschaftlichen Methodik und den hieraus neu gewonnenen Erkenntnissen beschäftigt sich diese Arbeit ebenso mit der Aufarbeitung naturphilosophischer Motive in den naturwissenschafts-historischen Kontext der Embryologie-Geschichte des frühen 19. Jahrhunderts gesetzt. / Christian Heinrich Pander was the founder of the germ layer theory in 1817 in Würzburg in Germany, Bavaria. Through his studies on the chick embryo he was able to describe a basic concept of the modern germ layer theory. In his practical studies with the microscope he received great support from Ignaz Döllinger, a professor in physiology and anatomy and a keen natural scientist at the University of Würzburg. Apart from analysing Panders scientific methods with the microscope and his gathered findings, this doctoral thesis also emphasizes the role of natural philosophy in Panders embryological studies in the context of the history of embryology in the early 19th century.