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  • 1.
    Cajander, Sara
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, article id R223Article in journal (Refereed)
    Abstract [en]

    Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

    Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

    Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

    Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

  • 2.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Rasmussen, Gunlög
    Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192883Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

    METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

    RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

    CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

  • 3.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Tina, Elisabet
    Örebro University, School of Medical Sciences.
    Magnuson, Anders
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences.
    Strålin, Kristoffer
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institute, Stockholm, Sweden .
    Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infectionManuscript (preprint) (Other academic)
  • 4.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Magnuson, Anders
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden .
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154690Article in journal (Refereed)
    Abstract [en]

    Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

    Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

    Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

    Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

  • 5. Gabrielson, Marike
    et al.
    Göthlin Eremo, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Karlsson, Elin
    Jakobsson, Frida
    Stål, Olle
    Wingren, Sten
    Regulation of cell proliferation and recurrence-free survival in HER2-positive breast cancer through SLC25A43 and p27Manuscript (preprint) (Other academic)
  • 6. Gabrielson, Marike
    et al.
    Reizer, Edwin
    Ståhl, Olle
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mitochondrial regulation of cell proliferation through SLC25A43 inHER2-positive breast cancer cells in vitroArticle in journal (Refereed)
  • 7.
    Gabrielson, Marike
    et al.
    School of Health and Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Reizer, Edwin
    School of Health and Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Stål, Olle
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Oncology, Linköping University, Linköping, Sweden.
    Tina, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Clinical Research Laboratory.
    Mitochondrial regulation of cell cycle progression through SLC25A432016In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, no 4, p. 1090-1096Article in journal (Refereed)
    Abstract [en]

    An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells.

    In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclear Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR.

    We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G(1)-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G(1)-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. (C) 2015 Elsevier Inc. All rights reserved.

  • 8.
    Gabrielson, Marike
    et al.
    Örebro Univ Hosp, Örebro, Sweden; School of Health & Medical Science, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    The mitochondrial transport protein SLC25A43 affects drug efficacy and drug-induced cell cycle arrest in breast cancer cell lines2013In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 4, p. 1268-Article in journal (Refereed)
    Abstract [en]

    The mitochondria have been identified as key players of apoptosis, cell proliferation and cell cycle regulation. However, the role of mitochondria in breast cancer and treatment failure remains unclear. We have previously shown a common deletion of the gene SLC25A43 in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This gene is coding for a mitochondrial inner membrane transporter and, to date, little is known about the function of this protein. We have also found that low protein expression of SLC25A43 significantly correlates with a lower S phase fraction in HER2-positive breast cancer. The aim of this study was to investigate whether knockdown (KD) of SLC25A43 could have an effect on the cytotoxicity of different cytostatic drugs using MCF10A, MCF7 and BT-474 cells. Following siRNA-mediated KD of SLC25A43, one non-malignant and two breast cancer cell lines were exposed to the anthracycline epirubicin or the taxane paclitaxel. The HER2-positive breast cancer cells were also exposed to the targeted therapy trastuzumab and dual exposure to trastuzumab and paclitaxel. We found that KD of SLC25A43 resulted in a decreased cytotoxic effect of paclitaxel in the two cancer cell lines (P<0.05). Further analysis of cell cycle phase distribution showed that KD increased the paclitaxel-induced G2/M block in these two cell lines (P<0.05). KD of SLC25A43 also reduced the inhibitory effect of trastuzumab on cell proliferation in the HER2-positive cancer cell line BT-474 (P<0.05), and the drug-induced G0/G1 block (P<0.05). Moreover, SLC25A43 influenced the percentage of Ki-67-positive cells. Our findings demonstrate that the mitochondrial protein SLC25A43 affects drug efficacy and cell cycle regulation following drug exposure in breast cancer cell lines.

  • 9.
    Göthlin Eremo, Anna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tina, Elisabet
    Örebro University Hospital. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Wegman, Pia
    Department of Clinical Genetics, University Hospital, Linköping, Sweden.
    Stål, Olle
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Fransén, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fornander, Tommy
    Department of Oncology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Regional Cancer Center Stockholm-Gotland, Stockholm, Sweden.
    Wingren, Sten
    Örebro University, School of Medicine, Örebro University, Sweden.
    HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen2015In: International Journal of Oncology, ISSN 1019-6439, Vol. 47, no 4, p. 1311-1320Article in journal (Refereed)
    Abstract [en]

    The human epidermal growth factor receptor (HER) 4 is a relative of HER2 and has been associated to endocrine breast cancer and prediction of tamoxifen response. In addition to PI3K/Akt and MAPK pathway activation, ligand binding to HER4 triggers proteolytic cleavage and release of an intracellular receptor domain (4ICD) with signaling properties. The aim of the present study was to analyze HER4 protein expression and intracellular localization in breast cancer tissue from patients randomized to treatment with or without adjuvant tamoxifen. To investigate HER4 expression and localization in response to estradiol (E2) and 4-hydroxytamoxifen (4-OHT) exposure, we also performed in vitro studies. Cytoplasmic, nuclear and membrane expression of HER4 protein was evaluated by immunohistochemical staining in tumor tissue from 912 breast cancer patients. Three different breast epithelia cancer cell lines were exposed to E2 and 4-OHT and mRNA expression was analyzed using qPCR. Further, nuclear and cytoplasmic proteins were separated and analyzed with western blotting. We found an association between nuclear HER4 protein expression and ER-positivity (P=0.004). Furthermore, significant association was found between cytoplasmic HER4 and ER-negativity (P<0.0005), PgR-negativity (P<0.0005), tumor size >20 mm (P=0.001) and HER2-negativity (P=0.008). However, no overall significance of HER4 on recurrence-free survival was found. After E2 exposure, HER4 mRNA and protein expression had decreased in two cell lines in vitro yet no changes in nuclear or cytoplasmic protein fractions were seen. In conclusion, nuclear HER4 seem to be co-located with ER, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment. The possible influence of separate isoforms was not tested and future studies may further evaluate HER4 significance.

  • 10.
    Kuchalik, Jan
    et al.
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders F.K.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Gupta, Anil
    Örebro University Hospital. Perioperative Medicine and Intensive Care, Institution for Physiology and Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Anesthesiology and Intensive Care Solna, Karolinska University Hospital, Stockholm, Sweden.
    Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty?: A randomized, double-blind study2017In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 17, article id 63Article in journal (Refereed)
    Abstract [en]

    Background: Postoperative inflammation following total hip arthroplasty (THA) can lead to delayed mobilization and return of hip function. Our primary aim was to assess whether local infiltration analgesia (LIA) during surgery can prevent postoperative inflammation.

    Methods: This is a sub-analysis of data from a broader double-blind study where 56 patients received spinal anaesthesia for THA. Additionally, Group FNB (Femoral Nerve Block) received an ultrasound-guided femoral nerve block using 30 mL of ropivacaine 7.5 mg/mL (225 mg), and 151.5 mL of saline peri-articularly intra-operatively. Group LIA received 30 mL saline in the femoral nerve block and ropivacaine 2 mg/mL, 300 mg (150 mL) + ketorolac 30 mg (1 mL) + adrenaline 0.5 mg (0.5 mL) peri-articularly. After 23 h, the LIA mixture (22 mL) was injected via a catheter placed peri-articularly in Group LIA and 22 mL saline in Group FNB. A battery of pro-and anti-inflammatory cytokines was assessed using a commercially available kit preoperatively and after 4 h and 3 days postoperatively. Additionally, CRP, platelet count and white blood count was determined pre- and postoperatively.

    Results: There was a general trend towards an increase in pro-inflammatory cytokines postoperatively, which returned to normal levels after 3 days. IL-6 concentration was significantly lower 4 h postoperatively in Group LIA compared to Group FNB (p = 0.015). No other significant differences were found between the groups in other cytokines. CRP levels were significantly higher in Group FNB compared to Group LIA 3 days postoperatively (p < 0.001). No other significant differences were seen between the groups.

    Conclusion: Local infiltration analgesia has a modest but short-lasting effect on postoperative inflammation in patients undergoing total hip arthroplasty. This is likely to be due to local infiltration of ketorolac and/or local anaesthetics in the LIA mixture. Future studies should be directed towards assessing whether the use of LIA translates into better patient outcomes.

  • 11.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Karolinska Institutet.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 10, p. 4071-4076Article in journal (Refereed)
    Abstract [en]

    Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase π (GSTπ) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.

    Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTπ were determined.

    Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTπ mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTπ mRNA in the resistant cells.

    Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTπ mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

  • 12.
    Prosén, Sara
    et al.
    Örebro University, School of Medical Sciences. Department of Dermatology, Örebro University Hospital, Örebro, Sweden.
    Göthlin Eremo, Anna
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Tsegai, Alexander Duarte
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindberg, Magnus
    Örebro University, School of Medical Sciences. Department of Dermatology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin2017In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 14, no 2, p. 2218-2222Article in journal (Refereed)
    Abstract [en]

    Basal cell carcinoma is the most common type of cancer in fair-skinned individuals, and its incidence is rapidly increasing. The aim of the present study was to investigate the gene and protein expression of the mitochondrial solute carrier family 25 member 43 (SLC25A43) in basal cell carcinoma. SLC25A43 has previously been identified to be genetically altered and associated with cell proliferation in human epidermal growth factor receptor 2-positive breast cancer. However, the knowledge about SLC25A43 is limited, and its role in other cancers is unknown. The SLC25A43 gene and protein expression was analysed in 14 basal cell carcinomas and healthy skin samples from the same individuals by quantitative polymerase chain reaction and immunohistochemistry, respectively. The results demonstrated a significantly lower (>= 50%) SLC25A43 gene expression in all carcinomas compared with that in healthy skin. In addition, SLC25A43 protein expression was absent in >90% of all visual fields in the basal cell carcinomas, and the H-score was significantly lower in tumours compared with the adjacent epidermis. These results demonstrate that SLC25A43 expression is altered at the gene and protein levels in basal cell carcinoma. The underlying mechanisms and the clinical relevance of these data must be elucidated in additional experimental and clinical studies.

  • 13.
    Siekmann, Wiebke
    et al.
    Örebro University, School of Medical Sciences. Anaesthesiology and Intensive Care, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Gupta, Anil
    Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Physiology and Pharma cology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Concentration-dependent cell viability and proliferation in vitro of colon cancer cell lines SW480 and SW620 on exposure to lidocaine or ropivacaine2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1017-1018Article in journal (Other academic)
    Abstract [en]

    Background: Cancer cells change phenotypes and properties when evolving from primary tumor cells to metastatic cells. These changes might affect the response to local anesthetics (LA). The aim of this study was to investigate if lidocaine or ropivacaine have a dose- dependent effect on cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro.

    Methods: The colon cancer cell lines SW 480, derived from primary tumor and SW620 from metastatic tumor in the same patient, were exposed to increasing log-concentrations of lidocaine and ropivacaine. Cell viability was measured using CellTiter Blue, and cell proliferation by PKH67, after exposure for up to 72 h.

    Results: Cell viability was not affected after 24 h of exposure. However, the metastatic cell line SW620 showed a significant increase in cell viability at low concentrati ons after 48 and 72 h. Exposure to the higher, but clinically relevant, concentrations of both LA resulted in decreased cell viability in both cell lines. These higher concentrations also showed an inhibitory effect on cell proliferation after 72 h, which was more pronounced for ropivacaine.

    Conclusions: Low concentrations of lidocaine and ropivacaine, as achieved in plasma by epidural infusion of LA, do not have direct antiproliferative effects on these colon cancer cell lines in vitro. Higher concentrations of LA, as during continuous local infiltration into tissues over 72 h, inhibit proliferation of both cancer cell lines. The increase in cell viability seen in SW620 should be investigated and underlying mechanisms further elucidated in future studies.

  • 14.
    Siekmann, Wiebke
    et al.
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory,.
    Koskela von Sydow, Anita
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Gupta, Anil
    Department of Physiology and Pharmacology, Karolinska Institute and Karolinska University Hospital, Stockholm; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines2019In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 18, no 1, p. 395-401Article in journal (Refereed)
    Abstract [en]

    Regional anesthesia may prolong survival following surgery for different types of cancers. The mechanisms behind this are unclear but direct effects on cancer cells by local anesthetics (LA) have been suggested. The aim of this study was to investigate if lidocaine or ropivacaine have a dose-dependent effect on the cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro. The colon cancer cell lines SW480 derived from primary tumor and SW620 from a metastatic site in the same patient were exposed to increasing concentrations of lidocaine and ropivacaine (5-1,000 mu M). Cell viability was measured using CellTiter-Blue((R)) and cell proliferation by PKH67 after exposure for up to 72 h. Cell viability was significantly reduced by ropivacaine at the highest concentration (1,000 mu M) after 48 and 72 h in the cell line SW480 and at 72 h in SW620. Exposure to lidocaine did not show any significant reduction in cell viability. Notably, low concentrations of both lidocaine and ropivacaine significantly increased cell viability after 48 and 72 h in SW620. Cell proliferation was significantly reduced by 1,000 mu M lidocaine in SW480 and by 1,000 mu M ropivacaine in SW620. In summary, both lidocaine and ropivacaine showed an anti-proliferative effect in the colon cancer cell lines at high concentrations and after prolonged exposure to LA in vitro. Our findings also indicate that lower concentrations promote cell viability in the metastatic cell line.

  • 15.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Biological markers in breast cancer and acute leukaemia with focus on drug resistance2010Doctoral thesis, comprehensive summary (Other academic)
    List of papers
    1. Topoisomerase II-α expression in different cell cycle phases in fresh human breast carcinomas
    Open this publication in new window or tab >>Topoisomerase II-α expression in different cell cycle phases in fresh human breast carcinomas
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    2002 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 15, no 5, p. 486-491Article in journal (Refereed) Published
    Abstract [en]

    Topoisomerase II-alfa (topo IIalfa) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo IIalfa is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo IIalfa is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo IIalfa in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo IIalfa was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA nondiploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 nondiploid tumors, >50% of the topo IIalfa–positive cells were in the G0/G1 phase. This significant expression of topo IIalfa in the G0/G1 phase of the cell cycle may have clinically important implications for treatment efficacy of topoisomerase II inhibitors.

    Place, publisher, year, edition, pages
    Baltimore: Lippincott Williams & Wilkins, 2002
    Keywords
    breast cancer, cell cycle, DNA flow cytometry, topoisomerase IIa
    National Category
    Medical and Health Sciences
    Research subject
    Medicine; Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10515 (URN)
    Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2017-12-12Bibliographically approved
    2. Topoisomerase IIα mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia
    Open this publication in new window or tab >>Topoisomerase IIα mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia
    Show others...
    2007 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 31, no 1, p. 153-160Article in journal (Refereed) Published
    Abstract [en]

    The objective of this study was to correlate the expression of topoisomerase (topo) IIalpha to in vitro drug sensitivity and to the clinical outcome in patients with acute leukaemia. Leukaemic cells were isolated from bone marrow or blood from 94 patients. Topo IIalpha mRNA (n=58) and protein (n=60) expression was determined by real-time RT-PCR and flow cytometry, respectively. In both groups, chemosensitivity testing by a bioluminescence ATP assay was performed to a variable extent for both topo IIalpha poisons and non-topo IIalpha targeting drugs. Topo IIalpha mRNA expression varied with relative values ranging from 0.03 to 14.20 (median 1.10). The median value for topo IIalpha protein-positive cells was 23% (range 0-99%). Cell samples from patients with a high (>median value) percentage of topo IIalpha-positive cells were significantly more sensitive to the topo IIalpha active drugs etoposide and daunorubicin, and showed a borderline value for idarubicin (p=0.08), while there was no difference for non-topo IIalpha targeting drugs. However, we did not find any significant differences in mRNA expression or the percentage of topo IIalpha-positive cells in patients who achieved complete remission after at most two induction courses compared with those who did not, nor did we find any difference in survival when patients with high mRNA expression/percentage of topo IIalpha-positive cells were compared with patients with low values. We conclude that expression of topo IIalpha, determined as percentage of topo IIalpha-positive cells, in leukaemic cells correlates to chemosensitivity in vitro against topoisomerase poisons but that it does not predict clinical outcome in acute leukaemia.

    Place, publisher, year, edition, pages
    Athens: Editorial Academy of the International Journal of Oncology, 2007
    Keywords
    topoisomerase IIa, acute leukaemia, drug resistance, prognosis, reverse transcriptase-polymerase chain reaction, flow cytometry
    National Category
    Medical and Health Sciences Cancer and Oncology
    Research subject
    Medicine; Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10516 (URN)17549416 (PubMedID)2-s2.0-34548571944 (Scopus ID)
    Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2017-12-12Bibliographically approved
    3. Topoisomerase IIalpha expression in acute myeloid leukaemia cells that survive after exposure to daunorubicin or ara-C
    Open this publication in new window or tab >>Topoisomerase IIalpha expression in acute myeloid leukaemia cells that survive after exposure to daunorubicin or ara-C
    Show others...
    2009 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 22, no 6, p. 1527-1531Article in journal (Refereed) Published
    Abstract [en]

    Patients diagnosed with acute myeloid leukaemia are often treated with a combination of daunorubicin and 1-β-D-arabinofuranosylcytosine (ara-C). Both daunorubicin and ara-C exert their effects in the cell nucleus but by different mechanisms, i.e. daunorubicin causes double stranded DNA breaks by inhibition of the nuclear enzyme, topoisomerase (topo) IIα, whereas ara-C is an anti-metabolite that integrates with DNA during DNA synthesis and causes cell cycle arrest. Despite the initial efficacy of these drugs, resistance often develops in the clinical setting. The mechanisms underlying clinical resistance to these drugs are poorly understood, but may be associated with an increase in the proportion of topo IIα negative cells. Therefore, the aim of this study was to determine whether daunorubicin treatment results in increased numbers of topo IIα negative subpopulations in vitro. Acute myeloid leukaemia cells isolated from 12 consenting patients were treated for 24 h with increasing concentrations of daunorubicin or ara-C and the proportion of topo IIα-negative cells in surviving cell populations determined by flow cytometry. Treatment with daunorubicin, but not ara-C, resulted in a significant increase in the proportion of topo IIα negative cells (p=0.0023). These results suggest that daunorubicin may act by cell cycle arrest and/or by selection of pre-existing topo IIα negative subpopulations. Both of these mechanisms can theoretically contribute to a reduced efficacy of a second dose of daunorubicin. The clinical relevance of these interactions should be further elucidated in experimental and clinical studies.

    Place, publisher, year, edition, pages
    Athen: Spandidos Publications, 2009
    Keywords
    acute myeloid leukaemia, topoisomerase, daunorubicin, 1-b-D-arabinofuranosylcytosine, flow cytometry
    National Category
    Medical and Health Sciences Cancer and Oncology
    Research subject
    Medicine; Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10517 (URN)10.3892/or_00000597 (DOI)000271732300035 ()19885609 (PubMedID)2-s2.0-70449353711 (Scopus ID)
    Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2017-12-12Bibliographically approved
    4. BCRP mRNA expression v. clinical outcome in 40 adult AML patients
    Open this publication in new window or tab >>BCRP mRNA expression v. clinical outcome in 40 adult AML patients
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    2005 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 29, no 2, p. 141-146Article in journal (Refereed) Published
    Abstract [en]

    Efflux pumps are considered being mechanisms behind drug resistance in acute myeloid leukaemia (AML). A recently described efflux pump, breast cancer resistance protein (BCRP), can be expressed in AML, but its clinical importance is uncertain. In this study BCRP mRNA expression was determined in samples from 40 AML patients by real-time RT-PCR. The expression varied from negative to 76 times that of control cells. There was no difference in BCRP mRNA expression between patients responding to induction treatment and non-responders. However, in the group of responders, the 14 patients with the highest expression had significantly shorter overall survival (mean 38 months, SEM 15 months) than the 14 patients with the lowest (74 months, SEM 16 months) (P = 0.047). This suggests a possible role of BCRP in drug resistance in AML.

    Place, publisher, year, edition, pages
    Amsterdam: Elsevier, 2005
    Keywords
    Breast cancer resistance protein, acute myeloid leukaemia, drug resistance, prognosis, reverse transcriptase polymerase chain reaction
    National Category
    Medical and Health Sciences
    Research subject
    Medicine; Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10518 (URN)10.1016/j.leukres.2004.06.004 (DOI)000226269500006 ()15607361 (PubMedID)2-s2.0-10644230985 (Scopus ID)
    Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2017-12-12Bibliographically approved
    5. A novel finding: SLC25A43 a solute carrier protein that is implicated in HER2 positive breast cancer
    Open this publication in new window or tab >>A novel finding: SLC25A43 a solute carrier protein that is implicated in HER2 positive breast cancer
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10471 (URN)
    Available from: 2010-04-26 Created: 2010-04-23 Last updated: 2017-10-18Bibliographically approved
  • 16.
    Tina, Elisabet
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Lindqvist, Breezy Malakkaran
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Gabrielson, Marike
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lubovac, Zelmina
    School of Life Sciences, University of Skövde, Skövde, Sweden.
    Wegman, Pia
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Wingren, Sten
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    The mitochondrial transporter SLC25A43 is frequently deleted and may influence cell proliferation in HER2-positive breast tumors2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, no 1, article id 350Article in journal (Refereed)
    Abstract [en]

    Background: Overexpression of the human epidermal growth factor receptor (HER) 2 is associated with poor prognosis and shortened survival in breast cancer patients. HER2 is a potent activator of several signaling pathways that support cell survival, proliferation and metabolism. In HER2-positive breast cancer there are most likely unexplored proteins that act directly or indirectly downstream of well established pathways and take part in tumor development and treatment response.

    Methods: In order to identify novel copy number variations (CNVs) in HER2-positive breast cancer whole-genome single nucleotide polymorphism (SNP) arrays were used. A PCR-based loss of heterozygosis (LOH) assay was conducted to verify presence of deletion in HER2-positive breast cancer cases but also in HER2 negative breast cancers, cervical cancers and lung cancers. Screening for mutations was performed using single-strand conformation polymorphism (SSCP) followed by PCR sequencing. Protein expression was evaluated with immunohistochemistry (IHC).

    Results: A common deletion at chromosome Xq24 was found in 80% of the cases. This locus harbors the gene solute carrier (SLC) family 25A member 43 (SLC25A43) encoding for a mitochondrial transport protein. The LOH assay revealed presence of SLC25A43 deletion in HER2-positive (48%), HER2-negative (9%), cervical (42%) and lung (67%) cancers. HER2-positive tumors with negative or low SLC25A43 protein expression had significantly lower S-phase fraction compared to tumors with medium or high expression (P = 0.024).

    Conclusions: We have found deletion in the SLC25A43 gene to be a common event in HER2-positive breast cancer as well as in other cancers. In addition, the SLC25A43 protein expression was shown to be related to S-phase fraction in HER2-positive breast cancer. Our results indicate a possible role of SLC25A43 in HER2-positive breast cancer and support the hypothesis of altered mitochondrial function in cancer.

  • 17.
    Tina, Elisabet
    et al.
    Örebro University, School of Health and Medical Sciences.
    Malakkaran [Lindqvist ], Breezy Paul
    Örebro University, School of Health and Medical Sciences.
    Gabrielson, Marike
    Örebro University, School of Health and Medical Sciences.
    Lubovac, Zelmina
    School of life sciences, University of Skövde, Sweden.
    Karlsson, Mats G.
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Stål, Olle
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden .
    Wegman, Pia
    Örebro University, School of Health and Medical Sciences.
    Wingren, Sten
    Örebro University, School of Health and Medical Sciences.
    A novel finding: SLC25A43 a solute carrier protein that is implicated in HER2 positive breast cancerManuscript (preprint) (Other academic)
  • 18.
    Tina, Elisabet
    et al.
    Örebro University, School of Health and Medical Sciences.
    Prenkert, Malin
    Örebro University, School of Health and Medical Sciences.
    Höglund, Martin
    Paul, Christer
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Topoisomerase IIalpha expression in acute myeloid leukaemia cells that survive after exposure to daunorubicin or ara-C2009In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 22, no 6, p. 1527-1531Article in journal (Refereed)
    Abstract [en]

    Patients diagnosed with acute myeloid leukaemia are often treated with a combination of daunorubicin and 1-β-D-arabinofuranosylcytosine (ara-C). Both daunorubicin and ara-C exert their effects in the cell nucleus but by different mechanisms, i.e. daunorubicin causes double stranded DNA breaks by inhibition of the nuclear enzyme, topoisomerase (topo) IIα, whereas ara-C is an anti-metabolite that integrates with DNA during DNA synthesis and causes cell cycle arrest. Despite the initial efficacy of these drugs, resistance often develops in the clinical setting. The mechanisms underlying clinical resistance to these drugs are poorly understood, but may be associated with an increase in the proportion of topo IIα negative cells. Therefore, the aim of this study was to determine whether daunorubicin treatment results in increased numbers of topo IIα negative subpopulations in vitro. Acute myeloid leukaemia cells isolated from 12 consenting patients were treated for 24 h with increasing concentrations of daunorubicin or ara-C and the proportion of topo IIα-negative cells in surviving cell populations determined by flow cytometry. Treatment with daunorubicin, but not ara-C, resulted in a significant increase in the proportion of topo IIα negative cells (p=0.0023). These results suggest that daunorubicin may act by cell cycle arrest and/or by selection of pre-existing topo IIα negative subpopulations. Both of these mechanisms can theoretically contribute to a reduced efficacy of a second dose of daunorubicin. The clinical relevance of these interactions should be further elucidated in experimental and clinical studies.

  • 19.
    Tina, Elisabet
    et al.
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Prosén, Sara
    Örebro University, School of Medical Sciences. Department of Dermatology, Örebro University hospital, Örebro, Sweden.
    Lennholm, S.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.
    Gasparyan, G.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.
    Lindberg, Magnus
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Dermatology, Örebro University hospital, Örebro, Sweden.
    Göthlin Eremo, Anna
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Expression profile of the amino acid transporters SLC7A5, SLC7A7, SLC7A8 and the enzyme TDO2 in basal cell carcinoma2019In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 180, no 1, p. 130-140Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of basal cell carcinoma (BCC) is increasing and the costs for care rising. Therefore, the need for simplified and cost-effective treatment choices is substantial. Aberrant signalling in several pathways, induced by ultraviolet radiation, is of importance in the development of BCC. Alterations in tumour metabolic activity are part of general carcinogenesis; however, these alterations are only partially recognized in skin cancer.

    Objectives: To study expression profiles in BCCs compared with individually matched nontumour skin, with a focus on finding differences associated with tumour metabolism.

    Materials and methods: Gene expression in biopsies from BCCs (n = 14) compared with biopsies from nontumour gluteal skin was analysed with microarrays (n = 4 + 4) and/or quantitative real-time polymerase chain reaction (qPCR, n = 14 + 14). Protein expression and localization was assessed using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded BCC samples.

    Results: Microarray analysis revealed increased expression of the amino acid transporters SLC7A5, SLC7A7 and SLC7A8 as well as the cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) 2 in BCC. Higher expression of SLC7A5 (P < 0.001), SLC7A8 (P < 0.001) and TDO2 (P = 0.002), but not SLC7A7 (P = 0.50), was confirmed by qPCR, and IHC demonstrated correlating tumour cell protein expression of SLC7A5 and SLC7A8. Protein expression of SLC7A7 was observed in the stratum granulosum, and TDO2 in immune cells.

    Conclusions: This study highlights the upregulation of SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply that amino acid transporters may be further explored as potential targets for future medical treatment.

  • 20.
    Uggla, Bertil
    et al.
    Department of Medicine, Örebro University Hospital, Örebro.
    Tina, Elisabet
    Clinical Research Centre, Örebro University Hospital, Örebro.
    Nahi, Hareth
    Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
    Paul, Christer
    Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
    Höglund, Martin
    Department of Haematology, Uppsala University Hospital, Uppsala,.
    Sirsjö, Allan
    Örebro University, Department of Clinical Medicine.
    Tidefelt, Ulf
    Örebro University, Department of Clinical Medicine. Department of Medicine, Örebro University Hospital, Örebro.
    Topoisomerase IIα mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 31, no 1, p. 153-160Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to correlate the expression of topoisomerase (topo) IIalpha to in vitro drug sensitivity and to the clinical outcome in patients with acute leukaemia. Leukaemic cells were isolated from bone marrow or blood from 94 patients. Topo IIalpha mRNA (n=58) and protein (n=60) expression was determined by real-time RT-PCR and flow cytometry, respectively. In both groups, chemosensitivity testing by a bioluminescence ATP assay was performed to a variable extent for both topo IIalpha poisons and non-topo IIalpha targeting drugs. Topo IIalpha mRNA expression varied with relative values ranging from 0.03 to 14.20 (median 1.10). The median value for topo IIalpha protein-positive cells was 23% (range 0-99%). Cell samples from patients with a high (>median value) percentage of topo IIalpha-positive cells were significantly more sensitive to the topo IIalpha active drugs etoposide and daunorubicin, and showed a borderline value for idarubicin (p=0.08), while there was no difference for non-topo IIalpha targeting drugs. However, we did not find any significant differences in mRNA expression or the percentage of topo IIalpha-positive cells in patients who achieved complete remission after at most two induction courses compared with those who did not, nor did we find any difference in survival when patients with high mRNA expression/percentage of topo IIalpha-positive cells were compared with patients with low values. We conclude that expression of topo IIalpha, determined as percentage of topo IIalpha-positive cells, in leukaemic cells correlates to chemosensitivity in vitro against topoisomerase poisons but that it does not predict clinical outcome in acute leukaemia.

  • 21. Welander, Edward
    et al.
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University, School of Health Sciences.
    Enonge Fotabe, Leslie
    Kardeby, Caroline
    Örebro University, School of Medical Sciences.
    Tina, Elisabet
    Örebro University, School of Medical Sciences.
    Elgbratt, Kristina
    Örebro University, School of Health Sciences.
    Pourlofti, Arvid
    Abawi, Akram
    Romild, Alma
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Crafoord, Jakob
    Ahlstrand, Erik
    Ivarsson, Mikael
    Örebro University, School of Health Sciences.
    Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis2018Conference paper (Refereed)
1 - 21 of 21
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