المؤلفون: Chuanyou Xia, Thale Kristin Olsen, A. Ali Zirakzadeh, Radwa Almamoun, Louise K. Sjöholm, Jenny Dahlström, Jan Sjöberg, Hans-Erik Claesson, John Inge Johnsen, Ola Winqvist, Dawei Xu, Tomas J. Ekström, Magnus Björkholm, Klas Strååt

المصدر: Frontiers in Oncology, Vol 10 (2020)

مصطلحات موضوعية: Hodgkin lymphoma, monozygotic triplets, DNA methylation, marginal zone-like B-cells, CD34+ cells, naïve B cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2020.598872/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/94f4986070ae4c41a106c7e70907ce02Test

المؤلفون: Göran Holm, Margareta Andersson, Monica Ekberg, Bengt Fagrell, Jan Sjöberg, Matteo Bottai, Magnus Björkholm

المصدر: PLoS ONE, Vol 9, Iss 12, p e113977 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: Larvae of the Northern pine processionary moth (Thaumetopoea pinivora, TP) carry microscopic needles (setae), which by penetrating skin and mucous membranes, may cause inflammatory/immune derived symptoms in man. In the present study the stimulatory effects of setae on human blood lymphocytes in vitro was investigated. Blood mononuclear cells were separated from venous blood or buffy coat of ten healthy individuals, six previously exposed to setae and four with no known exposure. Lymphoproliferation was measured as uptake of 3H-thymidine. Setae were prepared from TP larvae. Setae and saline setae extracts stimulated proliferation of T-lymphocytes in the presence of monocytic cells. Stimulation was pronounced in cells from persons who had been exposed to setae, and weak in cells from non-exposed donors. Chitin also induced lymphocyte proliferation in most donors, but to a lesser extent and independently of donor's previous exposure to setae. In conclusion, setae contain molecules that in the presence of monocytes activate human T-lymphocytes to proliferation. The antigenic nature of stimulatory molecules was supported by the significantly stronger lymphocyte response in persons previously exposed to setae than in non-exposed donors. The nature of such molecules remains to be defined.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4273998?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/600cfec456dc4009bc3e2a45541e5b66Test

المؤلفون: Hongya Han, Dawei Xu, Cheng Liu, Hans-Erik Claesson, Magnus Björkholm, Jan Sjöberg

المصدر: PLoS ONE, Vol 9, Iss 1, p e85085 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: Arachidonate 15-lipoxygenase-1 (ALOX15) oxygenates polyunsaturated fatty acids and bio-membranes, generating multiple lipid signalling mediators involved in inflammation. Several lines of evidence indicate that ALOX15 activation in the respiratory tract contributes to asthma progression. Recent experimental data reveals that histone modification at the promoter plays a critical role in ALOX15 gene transcription. In the present study, we examined the status of histone H3 trimethyl-lysine 27 (H3K27me3) at the ALOX15 promoter by chromatin immunoprecipitation assay in human lung epithelial carcinoma A549 cells incubated with or without interleukin (IL)-4. We identified demethylation of H3K27me3 at the ALOX15 promoter after IL-4 treatment. Furthermore, we found that the H3K27me2/3-specific demethylase, ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), mediates the H3K27me3 demethylation during ALOX15 transcriptional activation. When UTX expression was knocked down using siRNA, IL-4-mediated H3K27me3 demethylation and ALOX15 induction were significantly attenuated. The critical role of UTX in ALOX15 expression was confirmed in human monocytes and the Hodgkin lymphoma (HL) cell line L1236, but was in these cells not related to H3K27me3-demethylase activity. These results demonstrate that UTX is implicated in IL-4 mediated transcriptional activation of the ALOX15 gene.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3896354?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/65efcadc5f5f48c4a409bfceeac248baTest

المؤلفون: Cheng Liu, Dawei Xu, Hongya Han, Yidong Fan, Frida Schain, Zhonghua Xu, Hans-Erik Claesson, Magnus Björkholm, Jan Sjöberg

المصدر: PLoS ONE, Vol 7, Iss 12, p e52703 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: 15-Lipoxygenase-1 (15-LOX-1) oxidizes polyunsaturated fatty acids to a rich spectrum of biologically active metabolites and is implicated in physiological membrane remodelling, inflammation and apoptosis. Its deregulation is involved in the pathogenesis of diverse cancer and immune diseases. Recent experimental evidence reveals that dynamic histone methylation/demethylation mediated by histone methyltransferases and demethylases plays a critical role in regulation of chromatin remodelling and gene expression. In the present study, we compared the histone 3 lysine 4 (H3-K4) methylation status of the 15-LOX-1 promoter region of the two Hodgkin lymphoma (HL) cell lines L1236 and L428 with abundant and undetectable 15-LOX-1 expression, respectively. We identified a potential role of H3-K4 methylation in positive regulation of 15-LOX-1 transcription. Furthermore, we found that histone methyltransferase SMYD3 inhibition reduced 15-LOX-1 expression by decreasing promoter activity in L1236 cells. SMYD3 knock down in these cells abolished di-/trimethylation of H3-K4, attenuated the occupancy by the transactivator STAT6, and led to diminished histone H3 acetylation at the 15-LOX-1 promoter. In contrast, inhibition of SMCX, a JmjC-domain-containing H3-K4 tri-demethylase, upregulated 15-LOX-1 expression through induction of H3-K4 trimethylation, histone acetylation and STAT6 recruitment at the 15-LOX-1 promoter in L428 cells. In addition, we observed strong SMYD3 expression in the prostate cancer cell line LNCaP and its inhibition led to decreased 15-LOX-1 expression. Taken together, our data suggest that regulation of histone methylation/demethylation at the 15-LOX-1 promoter is important in 15-LOX-1 expression.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3532411?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/253879223640476f9d85abd308fbc75eTest

المؤلفون: Sigurdur Y. Kristinsson, Ola Landgren, Jan Sjöberg, Ingemar Turesson, Magnus Björkholm, Lynn R Goldin

المصدر: Haematologica, Vol 94, Iss 10 (2009)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

العلاقة: https://haematologica.org/article/view/5388Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test

الوصول الحر: https://doaj.org/article/01e7756526d34224bb329ff56fb65653Test

المؤلفون: Jan Sjöberg, Tom Wikman, Sven-Erik Hansen

المصدر: Norsk pedagogisk tidsskrift. 105:355-368

مصطلحات موضوعية: General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::5c51c976a537bc1448443f0fb0c3987eTest
https://doi.org/10.18261/issn.1504-2987-2021-03-08Test

المؤلفون: Ali Zirakzadeh, Magnus Björkholm, Ola Winqvist, Louise K. Sjöholm, Jan Sjöberg, Klas Strååt, Radwa Almamoun, Dawei Xu, Hans-Erik Claesson, Chuanyou Xia, Jenny Dahlström, John Inge Johnsen, Thale Kristin Olsen, Tomas J. Ekström

المصدر: Frontiers in Oncology, Vol 10 (2020)
Frontiers in Oncology

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, naïve B cells, Cd34 cells, Cell, Naive B cell, Disease, Biology, lcsh:RC254-282, switched memory B-cells, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, medicine, monozygotic triplets, DNA methylation, marginal zone-like B-cells, Brief Research Report, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, CD34+ cells, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Hodgkin lymphoma

الوصف: We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3d39d900565c6e0289cb488c2f4a6c6Test

المؤلفون: Jonas Bergh, Jorn Mulder, Mihaela Botezatu, Luca Moscetti, Filip Josephson, Ana Trullas Jimeno, Nikolaos Zafiropoulos, Paula van Hennik, Jan Sjöberg, Daniela Melchiorri, Harald Enzmann, Didier Meulendijks, Francesco Pignatti, Maja Sommerfelt Grønvold, Bjorg Bolstad, Jorge Camarero

المصدر: ESMO Open
ESMO Open, Vol 5, Iss 4 (2020)

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, EMA, European Medicine Agency, regulatory, renal cell cancer, Axitinib, Humans, Ipilimumab, Nivolumab, Carcinoma, Renal Cell, Kidney Neoplasms, medicine.drug_class, Pembrolizumab, Review, lcsh:RC254-282, Tyrosine-kinase inhibitor, law.invention, Avelumab, law, Internal medicine, Medicine, media_common.cataloged_instance, European union, media_common, Clinical pharmacology, business.industry, Carcinoma, Renal Cell, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, business, medicine.drug

الوصف: The therapeutic landscape in the treatment of advanced/metastatic renal cell cancer has evolved over the last 2 years with the advent of immune checkpoint inhibitors. In 2018 and 2019, marketing authorisations valid throughout the European Union were issued for nivolumab and ipilimumab dual checkpoint inhibition and pembrolizumab or avelumab in combination with the tyrosine kinase inhibitor axitinib. These applications presented numerous regulatory challenges. In this paper, we summarise the main regulatory considerations, originating from the assessment of the dossiers submitted from the applicants for the three combinations. The regulatory issues are grouped in four sections: clinical pharmacology, efficacy, biomarkers and safety. In each section, we describe the issues raised during the regulatory evaluation performed by the Committee for Medicinal Products for Human Use (CHMP) assessors. The CHMP assessments determine whether the medicines concerned meet the necessary quality, safety and efficacy requirements, and whether the benefit–risk balance is positive. In summary, although the overall benefit–risk was considered positive for the three combinations, the immaturity of the outcome data and the absence of long-term safety data remain issues to be addressed. Postauthorisation efficacy studies have been required to confirm the effects of the new combinations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::93da749197f6dc09a9c7c8e371fbfb64Test
http://europepmc.org/articles/PMC7451283Test

المؤلفون: Jonas Bergh, Paula van Hennik, Tomas Salmonson, Jan Sjöberg, Edward Laane, Kyriaki Tzogani, Christian Gisselbrecht, Pieter de Graeff, Francesco Pignatti, Ita Walsh, Annika Folin, Heinz Ludwig

المصدر: The Oncologist

مصطلحات موضوعية: Male, Regulatory Issues: EMA, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Antineoplastic Agents, Neutropenia, Placebo, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple myeloma, Panobinostat, Internal medicine, European Medicines Agency, medicine, Humans, media_common.cataloged_instance, European union, Adverse effect, Dexamethasone, media_common, Bortezomib, business.industry, medicine.disease, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Female, Erratum, Neoplasm Recurrence, Local, business, medicine.drug

الوصف: This article summarizes the scientific review of panobinostat that led to regulatory approval in the European Union.
On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD). Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks. The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double‐blind, placebo‐controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression‐free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31–0.72; log‐rank p value = .0003). The incidence of grade 3–4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3–4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7.9%), neutropenia (16.5%) and lymphopenia (8.1%). This article summarizes the scientific review of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landing_page.jsp&midTest=). Implications for Practice. Farydak was approved in the European Union in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD). The addition of panobinostat to bortezomib and dexamethasone resulted in a clinically meaningful and statistically significant improvement of progression‐free survival compared with bortezomib and dexamethasone, and an additional therapeutic option with a new mechanism of action was considered valuable. Although the toxicity associated with panobinostat combination was significant, at the time of the marketing authorization of panobinostat, it was considered that it was acceptable and that it should be left to the clinician and the patient to decide whether the panobinostat combination is the preferred treatment option or not.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3af7cbd290c7b1aa5d99a60e046ec8d9Test
https://doi.org/10.1634/theoncologist.2017-0301Test

المؤلفون: Chuanyou Xia, Thale Kristin Olsen, A. Ali Zirakzadeh, Radwa Almamoun, Louise K. Sjöholm, Jenny Dahlström, Jan Sjöberg, Hans-Erik Claesson, John Inge Johnsen, Ola Winqvist, Dawei Xu, Tomas J. Ekström, Magnus Björkholm, Klas Strååt

مصطلحات موضوعية: Cancer, Cancer Cell Biology, Cancer Diagnosis, Cancer Genetics, Cancer Therapy (excl. Chemotherapy and Radiation Therapy), Chemotherapy, Haematological Tumours, Molecular Targets, Radiation Therapy, Solid Tumours, Oncology and Carcinogenesis not elsewhere classified, Hodgkin lymphoma, monozygotic triplets, DNA methylation, marginal zone-like B-cells, CD34+ cells, naïve B cells, switched memory B-cells

الوصف: We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.

العلاقة: https://figshare.com/articles/dataset/DataSheet_1_Hodgkin_Lymphoma_Monozygotic_Triplets_Reveal_Divergences_in_DNA_Methylation_Signatures_pdf/13351919Test

الإتاحة: https://doi.org/10.3389/fonc.2020.598872.s001Test
https://figshare.com/articles/dataset/DataSheet_1_Hodgkin_Lymphoma_Monozygotic_Triplets_Reveal_Divergences_in_DNA_Methylation_Signatures_pdf/13351919Test