| 1. |
- Avdic, H. B., et al.
(författare)
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Reduced effects of social feedback on learning in Turner syndrome
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Turner syndrome is a genetic condition caused by a complete or partial loss of one of the X chromosomes. Previous studies indicate that Turner syndrome is associated with challenges in social skills, but the underlying mechanisms remain largely unexplored. A possible mechanism is a reduced social influence on learning. The current study examined the impact of social and non-social feedback on learning in women with Turner syndrome (n=35) and a sex- and age-matched control group (n=37). Participants were instructed to earn points by repeatedly choosing between two stimuli with unequal probabilities of resulting in a reward. Mastering the task therefore required participants to learn through feedback which of the two stimuli was more likely to be rewarded. Data were analyzed using computational modeling and analyses of choice behavior. Social feedback led to a more explorative choice behavior in the control group, resulting in reduced learning compared to non-social feedback. No effects of social feedback on learning were found in Turner syndrome. The current study thus indicates that women with Turner syndrome may be less sensitive to social influences on reinforcement learning, than the general population.
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| 2. |
- Krali, Olga, et al.
(författare)
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Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia
- 2023
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Ingår i: npj Precision Oncology. - : Springer Nature. - 2397-768X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.
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| 3. |
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| 4. |
- Nordlund, Jessica, et al.
(författare)
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DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
- 2015
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. Results: We used the methylation status of similar to 450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5. Conclusions: Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.
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| 5. |
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| 6. |
- Schoumans, Jacqueline, et al.
(författare)
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Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
- 2007
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
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| 7. |
- Wachtmeister, Alexandra, et al.
(författare)
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Cancer risk in individuals with polydactyly: a Swedish population-based cohort study
- 2024
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Ingår i: BRITISH JOURNAL OF CANCER. - 0007-0920 .- 1532-1827.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPolydactyly is a feature of several cancer predisposition syndromes (CPS), however, cancer risk in individuals with polydactyly is largely unknown.MethodsWe performed a matched cohort study using data from Swedish national registers. We included 6694 individuals with polydactyly, born in Sweden between 1970-2017. Polydactyly was categorised as thumb polydactyly, finger polydactyly, polydactyly+ (additional birth defects and/or intellectual disability) or isolated polydactyly. Each exposed individual was matched to 50 comparisons by sex, birth year and birth county. Associations were estimated through Cox proportional hazard models.FindingsAn increased childhood cancer risk was found in males (HR 4.24, 95% CI 2.03-8.84) and females (HR 3.32, 95% CI 1.44-7.63) with polydactyly+. Isolated polydactyly was associated with cancer in childhood (HR 1.87, 95% CI 1.05-3.33) and young adulthood (HR 2.30, 95% CI 1.17-4.50) in males but not in females. The increased cancer risk remained after exclusion of two known CPS: Down syndrome and neurofibromatosis. The highest site-specific cancer risk was observed for kidney cancer and leukaemia.ConclusionsAn increased cancer risk was found in individuals with polydactyly, especially in males and in individuals with polydactyly+. We encourage future research about polydactyly and cancer associations and emphasise the importance of clinical phenotyping.
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| 8. |
- Adlerberth, Ingegerd, 1959, et al.
(författare)
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Adhesins of Escherichia coli associated with extra-intestinal pathogenicity confer binding to colonic epithelial cells.
- 1995
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Ingår i: Microbial pathogenesis. - 0882-4010. ; 18:6, s. 373-85
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli adhesins are virulence factors in intestinal and extra-intestinal infections, but their role in normal intestinal colonization has not been defined. We investigated the intestinal adherence of E. coli with Dr hemagglutinin, S fimbriae, CFA/I or CFA/II, using freshly isolated ileal or colonic enterocytes and cells from the human colonic cell line HT-29. E. coli with S-fimbrial adhesins (Sfa I or Sfa II), P or type 1 fimbriae, adhered in a non-polarized manner, and in similar numbers to colonic and ileal enterocytes. S fimbriae of the variety Sfa II (originating from a meningitis isolate), mediated a stronger binding than Sfa I (of uropathogenic origin). Strains expressing Dr hemagglutinin adhered preferentially to the brush borders, slightly better to colonic than ileal enterocytes. Strains expressing CFA/I or II adhered to colonic and ileal enterocytes, although brush border adherence was predominantly observed with ileal cells. Binding to HT-29 cells paralleled binding to colonic enterocytes for all adhesin specificities except CFA/I. The results suggest that Dr hemagglutinin, P-, type 1- and S-fimbrial adhesins mediate binding to both colonic and ileal enterocytes. These specificities may contribute to the establishment of E. coli in the intestinal microflora, which precedes their spread to extra-intestinal sites.
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| 9. |
- Andersen, Mette K., et al.
(författare)
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Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13) : clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols
- 2011
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Ingår i: British Journal of Haematology. - Oxford : Wiley. - 0007-1048 .- 1365-2141. ; 155:2, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- The translocation t(1;19)(q23;p13)/der(19) t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19) t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 x 10(9)/l, and the female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10 years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was 0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19) t(1;19) (P = 0.004).
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| 10. |
- Anh, Nhi, et al.
(författare)
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High-resolution detection of chromosomal rearrangements in leukemias through mate pair whole genome sequencing
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- The detection of recurrent somatic chromosomal rearrangements is standard of care for most leukemia types. Even though karyotype analysis-a low-resolution genome-wide chromosome analysis-is still the gold standard, it often needs to be complemented with other methods to increase resolution. To evaluate the feasibility and applicability of mate pair whole genome sequencing (MP-WGS) to detect structural chromosomal rearrangements in the diagnostic setting, we sequenced ten bone marrow samples from leukemia patients with recurrent rearrangements. Samples were selected based on cytogenetic and FISH results at leukemia diagnosis to include common rearrangements of prognostic relevance. Using MP-WGS and in-house bioinformatic analysis all sought rearrangements were successfully detected. In addition, unexpected complexity or additional, previously undetected rearrangements was unraveled in three samples. Finally, the MP-WGS analysis pinpointed the location of chromosome junctions at high resolution and we were able to identify the exact exons involved in the resulting fusion genes in all samples and the specific junction at the nucleotide level in half of the samples. The results show that our approach combines the screening character from karyotype analysis with the specificity and resolution of cytogenetic and molecular methods. As a result of the straightforward analysis and high-resolution detection of clinically relevant rearrangements, we conclude that MP-WGS is a feasible method for routine leukemia diagnostics of structural chromosomal rearrangements.
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| 11. |
- Bang, Benedicte, et al.
(författare)
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A somatic UBA2 variant preceded ETV6-RUNX1 in the concordant BCP-ALL of monozygotic twins
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:7, s. 2275-2289
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Tidskriftsartikel (refereegranskat)abstract
- Genetic analysis of leukemic clones in monozygotic twins with concordant acute lymphoblastic leukemia (ALL) has proved a unique opportunity to gain insight into the molecular phylogenetics of leukemogenesis. Using whole-genome sequencing, we characterized constitutional and somatic single nucleotide variants/insertion-deletions (indels) and structural variants in a monozygotic twin pair with concordant ETV6-RUNX1(+) B-cell precursor ALL (BCP-ALL). In addition, digital PCR (dPCR) was applied to evaluate the presence of and quantify selected somatic variants at birth, diagnosis, and remission. A shared somatic complex rearrangement involving chromosomes 11, 12, and 21 with identical fusion sequences in leukemias of both twins offered direct proof of a common clonal origin. The ETV6-RUNX1 fusion detected at diagnosis was found to originate from this complex rearrangement. A shared somatic frameshift deletion in UBA2 was also identified in diagnostic samples. In addition, each leukemia independently acquired analogous deletions of 3 genes recurrently targeted in BCP-ALLs (ETV6, ATF7IP, and RAG1/RAG2), providing evidence of a convergent clonal evolution only explained by a strong concurrent selective pressure. Quantification of the UBA2 deletion by dPCR surprisingly indicated it persisted in remission. This, for the first time to our knowledge, provided evidence of a UBA2 variant preceding the well-established initiating event ETV6-RUNX1. Further, we suggest the UBA2 deletion exerted a leukemia predisposing effect and that its essential role in Small Ubiquitin-like Modifier (SUMO) attachment (SUMOylation), regulating nearly all physiological and pathological cellular processes such as DNA-repair by nonhomologous end joining, may hold a mechanistic explanation for the predisposition.
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| 12. |
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| 13. |
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| 14. |
- Batkovskyte, D., et al.
(författare)
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Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders
- 2023
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:5, s. 692-706
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Tidskriftsartikel (refereegranskat)abstract
- Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.
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| 15. |
- Bergstrand, Sofie, et al.
(författare)
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Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome
- 2020
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Ingår i: Cell Death and Disease. - : Nature Publishing Group. - 2041-4889. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Approximately half of all cases of Hoyeraal-Hreidarsson syndrome (HHS), a multisystem disorder characterized by bone marrow failure, developmental defects and very short telomeres, are caused by germline mutations in genes related to telomere biology. However, the varying symptoms and severity of the disease indicate that additional mechanisms are involved. Here, a 3-year-old boy with HHS was found to carry biallelic germline mutations in WRAP53 (WD40 encoding RNA antisense to p53), that altered two highly conserved amino acids (L283F and R398W) in the WD40 scaffold domain of the protein encoded. WRAP53 beta (also known as TCAB1 or WDR79) is involved in intracellular trafficking of telomerase, Cajal body functions and DNA repair. We found that both mutations cause destabilization, mislocalization and faulty interactions of WRAP53 beta, defects linked to misfolding by the TRiC chaperonin complex. Consequently, WRAP53 beta HHS mutants cannot elongate telomeres, maintain Cajal bodies or repair DNA double-strand breaks. These findings provide a molecular explanation for the pathogenesis underlying WRAP53 beta-associated HHS and highlight the potential contribution of DNA damage and/or defects in Cajal bodies to the early onset and/or severity of this disease.
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| 16. |
- Bjurling-Sjöberg, Petronella, 1968-, et al.
(författare)
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Resilient performance in healthcare during the COVID-19 pandemic (ResCOV) : study protocol for a multilevel grounded theory study on adaptations, working conditions, ethics and patient safety.
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Since early 2020, the COVID-19 pandemic has challenged societies and revealed the built-in fragility and dependencies in complex adaptive systems, such as healthcare. The pandemic has placed healthcare providers and systems under unprecedented amounts of strain with potential consequences that have not yet been fully elucidated. This multilevel project aims to explore resilient performance with the purpose of improving the understanding of how healthcare has adapted during the pandemic's rampage, the processes involved and the consequences on working conditions, ethics and patient safety.METHODS: An emerging explorative multilevel design based on grounded theory methodology is applied. Open and theoretical sampling is performed. Empirical data are gathered over time from written narratives and qualitative interviews with staff with different positions in healthcare organisations in two Swedish regions. The participants' first-person stories are complemented with data from the healthcare organisations' internal documents and national and international official documents.ANALYSIS: Experiences and expressions of resilient performance at different system levels and times, existing influencing risk and success factors at the microlevels, mesolevels and macrolevels and inter-relationships and consequences in different healthcare contexts, are explored using constant comparative analysis. Finally, the data are complemented with the current literature to develop a substantive theory of resilient performance during the pandemic.ETHICS AND DISSEMINATION: This project is ethically approved and recognises the ongoing strain on the healthcare system when gathering data. The ongoing pandemic provides unique possibilities to study system-wide adaptive capacity across different system levels and times, which can create an important basis for designing interventions focusing on preparedness to manage current and future challenges in healthcare. Feedback is provided to the settings to enable pressing improvements. The findings will also be disseminated through scientific journals and conferences.
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| 17. |
- Boström, Hans, et al.
(författare)
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U-2973, a novel B-cell line established from a patient with a mature B-cell leukemia displaying concurrent t(14;18) and MYC translocation to a non-IG gene partner
- 2008
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 81:3, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- B-cell lymphomas/leukemias with simultaneous t(14;18)(q32;q21) and MYC rearrangements have recently been shown to constitute a separate diagnostic entity, presenting with a rapid clinical course and a very poor prognosis. We describe the establishment of an Epstein-Barr virus negative cell line, designated U-2973, from a male patient with a de novo aggressive B-cell lymphoma/leukemia and very high peripheral blast cell count. Flow cytometry of bone marrow cells and U-2973 displayed a mature B-cell phenotype, and immunostaining showed expression of MYC and BCL2. IG gene rearrangement data were consistent with a lymphoid neoplasm of germinal centre derivation. Cytogenetic studies using conventional G-banding, fluorescent in situ hybridization, spectral karyotyping and single nucleotide polymorphism array demonstrated a complex karyotype with both a t(14;18) and double translocations between MYC and a non-IG gene partner located at chromosome 12p12.1.
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| 18. |
- Bremer, Anna, et al.
(författare)
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Copy number variation characteristics in subpopulations of patients with autism spectrum disorders.
- 2011
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Ingår i: American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 156B156:2, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P=0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs
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| 19. |
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| 20. |
- Curic, E., et al.
(författare)
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International Undiagnosed Diseases Programs (UDPs): components and outcomes
- 2023
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Ingår i: Orphanet Journal of Rare Diseases. - 1750-1172. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature. This exploration allowed for an assessment of the strengths and limitations of each of the six common steps, namely enrollment, comprehensive clinical phenotyping, research diagnostics, data sharing and matchmaking, results, and follow-up. Current literature highlights the potential utility of Undiagnosed Diseases Programs in research diagnostics. Since participants have often had extensive previous genetic studies, research pipelines allow for diagnostic approaches beyond exome or whole genome sequencing, through reanalysis using research-grade bioinformatics tools and multi-omics technologies. The overall diagnostic yield is presented by study, since different selection criteria at enrollment and reporting processes make comparisons challenging and not particularly informative. Nonetheless, diagnostic yield in an undiagnosed cohort reflects the potential of an Undiagnosed Diseases Program. Further comparisons and exploration of the outcomes of Undiagnosed Diseases Programs worldwide will allow for the development and improvement of the diagnostic and research process and in turn improve the value and utility of an Undiagnosed Diseases Program.
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| 21. |
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| 22. |
- Delbro, Dick, et al.
(författare)
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Is acetylcholine an autocrine/paracrine growth factor via the nicotinic α-receptor subtype in the human colon cancer cell line HT-29?
- 2009
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 609:1-3, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- We used immunochemistry to demonstrate expression of acetylcholine's nicotinic 7-receptor subtype inhuman colon cancer cell line HT-29. Moreover, RT-PCR and immunochemistry showed that cholineacetyltransferase and acetylcholine esterase, the enzymes responsible for acetylcholine synthesis anddegradation, respectively, localise in HT-29 cells. Bromoacetylcholine bromide, an inhibitor of cholineacetyltransferase, significantly attenuated basal cell growth. Our findings suggest that acetylcholine mightserve as an autocrine/paracrineor speculatively, even intracrinesignalling molecule in cell line HT-29, thuscontributing to carcinogenesis/cancer progression
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| 23. |
- Delbro, Dick, et al.
(författare)
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Nuclear expression of mu-opioid receptors in a human mesothelial cell line
- 2009
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Ingår i: Autonomic & Autacoid Pharmacology. - : Wiley. - 1474-8665 .- 1474-8673. ; 29:4, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- 1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation ofexperimentally induced postoperative abdominal adhesions in rats. Mesothelial cells mayparticipate in adhesion formation by secreting mediators that interfere negatively withfibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesionmediators from mesothelial cells. This study aimed to investigate whether human mesothelialcells express MOR-1; if so, such could constitute a site of action for morphine in adhesionprevention.2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared forimmunocytochemistry and Western blotting.3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in thenuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to thoseobtained with a control lysate from cells known to express MORs. In addition, we foundMOR-1 expression with nuclear and cytoplasmatic localization in biopsies from humanabdominal adhesions.4 The current findings may suggest that morphine could interact directly with mesothelial cellsvia MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering withthe release of pro-adhesion factors from these cells
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| 24. |
- Diffner, Eva, et al.
(författare)
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Expression of VEGF and VEGF Receptors in Childhood Precursor B-cell Acute Lymphoblastic Leukemia Evaluated by Immunohistochemistry
- 2009
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Ingår i: Journal of pediatric hematology/oncology (Print). - : Wolters Kluwer. - 1077-4114 .- 1536-3678. ; 31:9, s. 696-701
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Tidskriftsartikel (refereegranskat)abstract
- Perturbation in the expression and signaling pathways of vascular endothelial growth factor (VEGF) has been linked to pathogenesis of hematologic malignancies. We investigated the expression and clinical importance of VEGF and two of its receptors, VEGFR-1 and VEGFR-2, in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL) by using immunohistochemistry. These angiogenic proteins were expressed in the majority of leukemic bone marrow samples. Notably, pre-B ALL patients had significantly increased expression of VEGFR-1 compared with no expression in the nonmalignant group, indicating a link between VEGFR-1 protein expression and pre-B ALL. These novel findings suggest that VEGFR-1 may have clinical importance in childhood pre-B ALL.
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| 25. |
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