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Sökning: WFRF:(Ingvar M) > Linköpings universitet

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1.
  • Kosek, Eva, et al. (författare)
  • The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia
  • 2016
  • Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 58, s. 218-227
  • Tidskriftsartikel (refereegranskat)abstract
    • The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n = 126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n = 24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p = 0.016) and fibromyalgia symptoms (p = 0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p < 0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception.
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  • Nilsson, K., et al. (författare)
  • Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial
  • 2023
  • Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:11, s. 1015-1024
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer.Patients and methods: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type.Results: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107).Conclusion: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.
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  • Ansell, Anna, et al. (författare)
  • Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts
  • 2013
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor stroma and are known to increase tumor growth and stimulate  invasion and metastasis. Increasing evidence suggests that CAFs may also be an important determinant of the response to various treatments. In this study we aimed to characterize the molecular cross-talk between CAFs and head and neck squamous cell carcinoma (HNSCC) cells.HNSCC cell lines were co-cultured with their patient-matched CAFs for seven days, after which the gene expression of tumor cells was investigated by Affymetrix microarray. 58 protein coding genes were found to be differentially expressed (Q≤0.05) in tumor cells cocultured with CAFs when compared to tumor cells cultured alone. The top functions of these genes were cancer, cellular movement, and embryonic development as analyzed by Ingenuity Pathway Analysis. Nine genes were upregulated by ≥1.5-fold while the expression of 35 genes was found to be reduced by ≤ 0.67-fold. Several of the differentially expressed genes have been associated with epithelial-to-mesenchymal transition (EMT). The change in the expression of POSTN, GREM1, COL1A2, VIM, and MMP7 was verified by qPCR analysis. Moreover, the influence of CAFs on the proliferation, migration and cetuximab sensitivity of tumor cells was investigated, and was found to vary among the tumor cell-CAF pairs.In conclusion, we demonstrate that CAF-derived signals cause changes in the expression of multiple genes, several of which are associated with an EMT phenotype of tumor cells. Furthermore, CAFs modulate the proliferation, migration and cetuximab treatment response of tumor cells.
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6.
  • Cohn-Cedermark, G, et al. (författare)
  • Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm
  • 2000
  • Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 89:7, s. 1495-1501
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS, The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and less than or equal to 2 mm. Patients were allocated randomly to a 2-cm excision margin or a 5-cm excision margin. In total, 989 patients were recruited during the period 1982-1991. The median follow-up, was 11 years (range, 7-17 years) for estimation of survival and 8 years (range, 0-17 years) for evaluation of recurrent disease. RESULTS. The crude rate of local recurrence, defined as a recurrence in the scar or transplant, was < 1% (8 of 989 patients). Twenty percent of the patients (194 of 989 patients) experienced any disease recurrence, and 15% (146 of 989 patients) died of melanoma. There were no statistically significant differences between the two treatment arms. In a multivariate Cox analysis with patients allocated to wide excision as the reference group, the estimated relative hazards for overall survival and recurrence free survival among those allocated to a 2-cm resection margin were 0.96 (95% confidence interval, 0.75-1.24), and 1.02 (95% confidence interval, 0.80-1.30), respectively. CONCLUSIONS. In this long term follow-up study, local recurrences were found to be rare among patients with tumors > 0.8 mm thick and less than or equal to 2.0 mm thick. Mo difference in recurrence rate or survival between the two treatment groups was found. Patients in this category can be treated with a resection margin of 2 cm as safely as with a resection margin of 5 cm. Cancer 2000,89:1495-501. (C) 2000 American Cancer Society.
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7.
  • Halvarsson, Camilla, et al. (författare)
  • Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1 alpha (HIF-1 alpha) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types. It has not been established whether PDK1 is essential for HSC function and mediates hypoxia-adapting functions in HSCs. While the Pdk gene family contains four members (Pdk1-4), it was recently shown that Pdk2 and Pdk4 have an important role in regulating LT-HSCs. Principle findings Here we demonstrate that PDK1 activity is crucial for transplantable HSC function. Whereas Pdkl, Pdk2, and Pdk3 transcripts were expressed at higher levels in different subtypes of HSCs compared to differentiated cells, we could not detect any major differences in expression between LT-HSCs and more short-term HSCs and multipotent progenitors. When studying HIF-1 alpha-mediated regulation of Pdk activity in vitro, Pdk1 was the most robust target regulated by hypoxia, whereas Pdk2, Pdk3, and Pdk4 were not affected. Contrary, genetic ablation in a cre-inducible Hif-1 alpha knockout mouse did not support a link between HIF-1 alpha and Pdk1. Silencing of Pdk1 by shRNA lentiviral gene transfer partially impaired progenitor colony formation in vitro and had a strong negative effect on both long-term and short-term engraftment in mice. Conclusions Our study demonstrates that PDK1 has broad effects in hematopoiesis and is a critical factor for engraftment of both HSCs and multipotent progenitors upon transplantation to recipient mice. While Pdk1 was a robust hypoxia-inducible gene mediated by HIF-1 alpha in vitro, we could not find evidence of any in vivo links between Pdk1 and HIF-1 alpha.
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8.
  • Hasselgren, Kristina, et al. (författare)
  • Does the Introduction of Laparoscopic Distal Pancreatectomy Jeopardize Patient Safety and Well-Being?
  • 2016
  • Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 105:4, s. 223-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Purpose: Despite retrospective data indicating short-term superiority for laparoscopic distal pancreatectomy compared to open distal pancreatectomy, the implementation of the procedure has been slow. The aim of this study was to investigate whether patients operated with laparoscopic distal pancreatectomy during the early phase of introduction are at higher risk for complications than patients operated with open distal pancreatectomy.Methods: A retrospective single-center analysis of patients operated with laparoscopic distal pancreatectomy (n=37) from the introduction of the procedure and comparison regarding demographic data, preoperative data, operative factors, and postoperative outcomes to patients operated with open distal pancreatectomy was done.Results: Operation duration shortened (195 vs 143min, p=0.04) and severe complications reduced (37% vs 6%, p=0.02) significantly in the laparoscopic distal pancreatectomy group between the first half of the study and the second half. Blood loss was significantly (pamp;lt;0.001) lower in the laparoscopic distal pancreatectomy group (75mL) than in the open distal pancreatectomy group (550mL), while complication rate and hospital stay as well as the percentage of radical resections were the same.Conclusion: Laparoscopic distal pancreatectomy can be introduced without jeopardizing patient safety and well-being during the early learning curve. The procedures should be compared in a prospective randomized manner.
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9.
  • Heiervang, Einar, et al. (författare)
  • Psychiatric disorders in Norwegian 8- to 10-year-olds: an epidemiological survey of prevalence, risk factors, and service use.
  • 2007
  • Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 46:4, s. 438-447
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The Bergen Child Study is a longitudinal study of child mental health from the city of Bergen, Norway. We present methods and results from the first wave of the study, focusing on prevalence of disorders, associations with risk factors, and the use of services. METHOD: The target population included all 9,430 children attending grades 2 to 4 in Bergen schools during the academic year 2002/2003. The main screening instrument was the Strengths and Difficulties Questionnaire, whereas diagnoses were based on the Development and Well-Being Assessment. Information about child and family risk factors and service use was also obtained in this second stage. RESULTS: In the first phase, the teacher Strengths and Difficulties Questionnaire was obtained for 9,155 (97%) of the target children and the matching parent Strengths and Difficulties Questionnaire for 6,297 (67%); 1,011 children (11%) were assessed with the Development and Well-Being Assessment in the second phase. The weighted prevalence for any DSM-IV psychiatric disorder was 7.0% (95% confidence interval 5.6%-8.5%). Disorders were associated with age, gender, learning difficulties, family type, and poverty. Although 75% of children with attention-deficit/hyperactivity disorder had been in contact with specialist mental health services, this was true for only 13% of those with pure emotional disorders. CONCLUSIONS: The overall prevalence of psychiatric disorders in children is relatively low in this Norwegian sample, when assessed with the Development and Well-Being Assessment. Children with emotional disorders have limited access to specialist services.
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10.
  • Holmberg, Carl Jacob, et al. (författare)
  • Prognostic Significance of Sentinel Lymph Node Status in Thick Primary Melanomas (> 4 mm)
  • 2023
  • Ingår i: Annals of Surgical Oncology. - : SPRINGER. - 1068-9265 .- 1534-4681.
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe key prognostic factors for staging patients with primary cutaneous melanoma are Breslow thickness, ulceration, and sentinel lymph node (SLN) status. The multicenter selective lymphadenectomy trial (MSLT-I) verified SLN status as the most important prognostic factor for patients with intermediate-thickness melanoma (Breslow thickness, 1-4 mm). Although most international guidelines recommend SLN biopsy (SLNB) also for patients with thick (> 4 mm, pT4) melanomas, its prognostic role has been questioned. The primary aim of this study was to establish whether SLN status is prognostic in T4 melanoma tumors.MethodsData for all patients with a diagnosis of primary invasive cutaneous melanoma of Breslow thickness greater than 1 mm in Sweden between 2007 and 2020 were retrieved from the Swedish Melanoma Registry, a large prospective population-based registry. A multivariable Cox proportional hazard model for melanoma-specific survival (MSS) was constructed based on Breslow thickness stratified for SLN status.ResultsThe study enrolled 10,491 patients, 1943 of whom had a Breslow thickness greater than 4 mm (pT4). A positive SLN was found for 34% of these pT4 patients. The 5-year MSS was 71%, and the 10-year MSS was 62%. There was a statistically significant difference in MSS between the patients with a positive SLN and those with a negative SLN (hazard ratio of 2.4 (95% confidence interval CI 1.6-3.5) for stage T4a and 2.0 (95% CI 1.6-2.5) for satage T4b.ConclusionSentinel lymph node status gives important prognostic information also for patients with thick (> 4 mm) melanomas, and the authors thus recommend that clinical guidelines be updated to reflect this.
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