8 research outputs found
Personlighetstestning som metod vid rekrytering
Detta Àr en kvalitativ studie som  kartlÀgger synen pÄ personlighet inom sex olika företag inom rekryteringsbranschen. Studien beskriver hur och i vilket syfte personlighetstester anvÀnds samt vilken betydelse de har i rekryteringsprocessen för chefsrekryteringar. UtifrÄn denns studie kan vi kunde vi att personlighetstester anvÀnds för att kartlÀgga personligheten i syfte att göra en matchning med kravprofilen för att se om personen har de kvaliteter som önskas i ett rekryteringssammanhang. Vi fann dock en tveksamhet inför att vilja uttrycka personlighetstesters tyngd i urvalet. Vi kom ocksÄ fram till att informanterna hade delade meningar om huruvida det Àr den objektiva eller den subjektiva bilden av personen som Àr av vÀrde för att prognostisera framtida beteenden. UtifrÄn denna diskurs stÀller vi oss undrande till om det Àr kandidatens sjÀlvuppskattade bild eller omgivningens uppfattning som borde vara mest relevant för en lyckad rekrytering. Vidare fann vi att intervjuer enligt de flesta av vÄra informanterna har större betydelse för det slutgiltiga urvalet i rekryteringsprocessen Àn personlighetstester. Vad som dock Àr intressant att pÄpeka Àr att testresultatet ligger till grund för vad som diskuteras under intervjun och pÄ sÄ vis fÄr en styrande funktion.
Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with Lu-177-octreotate
Background: The kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with Lu-177-[DOTA(0), Tyr(3)]-octreotate (Lu-177-octreotate), despite the successful use of kidney uptake blocking agents such as lysine and arginine. To avoid renal toxicity but still give each patient as high amount of Lu-177-octreotate as possible, there is a need for methods/biomarkers that indicate renal injury in an early stage of the treatment. The aim of this study was to investigate the potential of using urinary retinol binding protein 4 (RBP4) and carbamoylated haemoglobin (Hb) in blood as biomarkers of nephrotoxic effects on adult mice after Lu-177-octreotate treatment. Methods: Adult BALB/c nude mice were injected with 60 MBq or 120 MBq of Lu-177-octreotate or with saline (control). Urine was collected before injection and concentrations of urinary RBP4 and creatinine were determined 14 to 90 days after injection Blood samples were collected after 90 days, and carbamoylated N-terminal valine in Hb, formed from urea, was measured as valine hydantoin (VH) after detachment from Hb. Results: The RBP4 values increased with administered activity and time. For the 60 and 120 MBq groups, statistically significantly higher RBP4 levels (p 0.05). No morphological changes in the kidney tissue were found. Conclusions: Urinary RBP4 is a promising new biomarker for radiation-induced renal toxicity. For the conditions used in this experiment, carbamoylated Hb (from urea) measured as VH may not be a sufficiently sensitive biomarker to be used for renal toxicity
Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (
Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (
Transcriptional effects of 177Lu-octreotate therapy using a priming treatment schedule on GOT1 tumor in nude mice
Abstract Background 177Lu-octreotate is used for therapy of somatostatin receptor expressing neuroendocrine tumors with promising results, although complete tumor remission is rarely seen. Previous studies on nude mice bearing the human small intestine neuroendocrine tumor, GOT1, have shown that a priming injection of 177Lu-octreotate 24âh before the main injection of 177Lu-octreotate resulted in higher 177Lu concentration in tumor, resulting in increased absorbed dose, volume reduction, and time to regrowth. To our knowledge, the cellular effects of a priming treatment schedule have not yet been studied. The aim of this study was to identify transcriptional changes contributing to the enhanced therapeutic response of GOT1 tumors in nude mice to 177Lu-octreotate therapy with priming, compared with non-curative monotherapy. Results RNA microarray analysis was performed on tumor samples from GOT1-bearing BALB/c nude mice treated with a 5âMBq priming injection of 177Lu-octreotate followed by a second injection of 10âMBq of 177Lu-octreotate after 24âh and killed after 1, 3, 7, and 41Â days after the last injection. Administered activity amounts were chosen to be non-curative, in order to facilitate the study of tumor regression and regrowth. Differentially regulated transcripts (RNA samples from treated vs. untreated animals) were identified (change â„â1.5-fold; adjusted p value <â0.01) using Nexus Expression 3.0. Analysis of the biological effects of transcriptional regulation was performed using the Gene Ontology database and Ingenuity Pathway Analysis. Transcriptional analysis of the tumors revealed two stages of pathway regulation for the priming schedule (up to 1Â week and around 1Â month) which differed distinctly from cellular responses observed after monotherapy. Induction of cell cycle arrest and apoptotic pathways (intrinsic and extrinsic) was found at early time points after treatment start, while downregulation of pro-proliferative genes were found at a late time point. Conclusions The present study indicates increased cellular stress responses in the tumors treated with a priming treatment schedule compared with those seen after conventional 177Lu-octreotate monotherapy, resulting in a more profound initiation of cell cycle arrest followed by apoptosis, as well as effects on PI3K/AKT-signaling and unfolded protein response
Priming increases the anti-tumor effect and therapeutic window of 177 Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1
Abstract
Background
177
Lu-[DOTA
0
, Tyr
3
]-octreotate (
177
Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1 , 2 and 5 , and increase
177
Lu-octreotate uptake.
The aim of the present study was to examine the anti-tumor effect of a
177
Lu-octreotate priming dose followed 24\ua0h later by a second injection of
177
Lu-octreotate compared to a single administration of
177
Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice.
Results
Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE , BAX , CDKN1A , and GADD45A .
Conclusions
Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for
177
Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects