Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

BACKGROUND: Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. METHODS: The patients were genotyped using PCR followed by cleavage with restriction enzymes. RESULTS: Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). CONCLUSION: The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort

”Renen kan inte äta pengar. En gruva påverkar allt.” : En idéanalytisk studie om gottgörande rättvisa och samers rättigheter i fallen Rönnbäck/Rönnbäcken och Gállok/Kallak

This thesis scrutinises the state plans for future mining operations in two specific areas in northern Sweden, namely Rönnbäck/Rönnbäcken and Gállok/Kallak, and how these plans have become issues of intense dialogues and debates nationwide during the previous years. This is partly because of environmental reasons but the primary matter is because these two areas have traditionally belonged to the indigenous Saami people where they are pursuing reindeer husbandry. Despite the many voices of the Swedish society as well as the Saami people that have been raised against the mining plans in these two specific areas, the Swedish government still approved the mining companies to start pursing their activities in both cases. Because of this, several human rights issues have been invoked against the Swedish state in terms of the directly affected Saami’s rights as an indigenous people. Some of these invocations have been made by referring to the ICERD and UNDRIP. Therefore, on the basis of the Saami’s right to fair rectification as an indigenous people, the aim of this work is to further examine how state actions for rectification, because of previous state conducted human rights violations, are being perceived by different actors; in this case the Swedish state and the Saami people. By applying the theoretical framework of rectificatory justice, and conducting the method of analysing the arguments and perceptions of the Saami people as well as the Swedish state, the main focus of the thesis is to further examine the two cases of Rönnbäck/Rönnbäcken and Gállok/Kallak. The thesis’ main finding is that there are many discrepancies between the Saami people and the Swedish state in terms of their views on fair rectificatory arrangements as well as the rights of the Saami as an indigenous people

UNIVERSITETSLÄRARES FÖRVÄNTNINGAR PÅ NYBLIVNA STUDENTER : En kvalitativ intervjustudie

Befolkningen i Sverige blir mer och mer högutbildad och de senaste åren har vi sett en stadig ökning av antalet medborgare med en eftergymnasial examen. Samtidigt som allt fler väljer att läsa vidare efter gymnasieskolan så är det en förhållandevis hög andel som aldrig fullföljer sina studier och avhoppen från högre utbildning är särskilt hög under utbildningarnas första år. Detta väcker frågan om studenterna är tillräckligt förberedda för högre studier. Detta är särskilt intressant utifrån biologiämnet, då många som läser biologi inom gymnasieskolan också väljer att läsa vidare. Syftet med denna studie är därför att undersöka vilka förväntningar lärare inom biologi vid universitet och högskola har på sina nyantagna studenter och hur dessa förväntningar förhåller sig till ämnesplanen för biologi i gymnasieskolan. Genom fem semistrukturerade intervjuer med lärare inom universitet och högskola som undervisar biologi har frågan här behandlats. En tematisk analys av intervjuerna visar att studenternas ansvarstagande, studieteknik och intresse är de tydligaste förväntningarna från universitet- och högskolelärarna. Att studenterna även förväntas ha goda färdigheter och ämneskunskaper i andra ämnen än just biologi är också tydligt, vilket dessutom är den förväntning som i minst grad uppfylls. Hur väl lärarnas förväntningar överensstämmer med ämnesplanen för biologi och även vilka faktorer som är viktigast för gymnasieelevers framtida studier diskuteras och presenteras ur en internationell kontext. För att bättre förbereda gymnasieelever för högre studier behövs en ökad samsyn mellan universitet och gymnasium och det finns dessutom många faktorer vars roll för studenternas högskoleförberedelse inte är klargjord

”Renen kan inte äta pengar. En gruva påverkar allt.” : En idéanalytisk studie om gottgörande rättvisa och samers rättigheter i fallen Rönnbäck/Rönnbäcken och Gállok/Kallak

This thesis scrutinises the state plans for future mining operations in two specific areas in northern Sweden, namely Rönnbäck/Rönnbäcken and Gállok/Kallak, and how these plans have become issues of intense dialogues and debates nationwide during the previous years. This is partly because of environmental reasons but the primary matter is because these two areas have traditionally belonged to the indigenous Saami people where they are pursuing reindeer husbandry. Despite the many voices of the Swedish society as well as the Saami people that have been raised against the mining plans in these two specific areas, the Swedish government still approved the mining companies to start pursing their activities in both cases. Because of this, several human rights issues have been invoked against the Swedish state in terms of the directly affected Saami’s rights as an indigenous people. Some of these invocations have been made by referring to the ICERD and UNDRIP. Therefore, on the basis of the Saami’s right to fair rectification as an indigenous people, the aim of this work is to further examine how state actions for rectification, because of previous state conducted human rights violations, are being perceived by different actors; in this case the Swedish state and the Saami people. By applying the theoretical framework of rectificatory justice, and conducting the method of analysing the arguments and perceptions of the Saami people as well as the Swedish state, the main focus of the thesis is to further examine the two cases of Rönnbäck/Rönnbäcken and Gállok/Kallak. The thesis’ main finding is that there are many discrepancies between the Saami people and the Swedish state in terms of their views on fair rectificatory arrangements as well as the rights of the Saami as an indigenous people

Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma

Background: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells. Case presentations: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-γ) and IL-1α, for the 3 renal cell carcinoma cases compared with healthy blood donors. Conclusions: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma