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  • 1.
    Bergström, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Cui, Tao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Nystrand, Mats
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Microarray Immunoassay Development to Specifically Detect Autoantibodies in Small Intestine Neuroendocrine Tumor (SI-NET) Patients2013Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, nr 2, s. 369-370Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Cui, Tao
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Hurtig, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Elgue, Graciela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Veronesi, Giulia
    Essaghir, Ahmed
    Demoulin, Jean-Baptiste
    Pelosi, Giuseppe
    Alimohammadi, Mohammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Öberg, Kjell
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Giandomenico, Valeria
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors2010Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 12, s. e16010-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. Methodology/Principal Findings: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Conclusion: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

     

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  • 3.
    Cui, Tao
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tsolakis, Apostolos V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olfactory Receptor 51E1 is a Potential Novel Tissue Biomarker for the Diagnosis of Small Intestine Neuroendocrine Tumors2013Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, nr 2, s. 373-373Artikkel i tidsskrift (Annet vitenskapelig)
  • 4.
    Cui, Tao
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Tsolakis, Apostolos V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olfactory receptor 51E1 is a potential novel tissue biomarker for the diagnosis and prognosis of small intestine neuroendocrine tumors2012Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 177, nr Suppl, s. S18-S18Artikkel i tidsskrift (Annet vitenskapelig)
  • 5.
    Cui, Tao
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Tsolakis, Apostolos V
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Cunningham, Janet L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas2013Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 168, nr 2, s. 253-261Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker.

    DESIGN: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor.

    RESULTS: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in >50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor.

    CONCLUSION: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.

  • 6.
    Darmanis, Spyros
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cui, Tao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Drobin, Kimi
    KTH - Royal Institute of Technology, Stockholm, Sweden.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH - Royal Institute of Technology, Stockholm, Sweden.
    Schwenk, Jochen M.
    KTH - Royal Institute of Technology, Stockholm, Sweden.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, s. e81712-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NET) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required.

    Materials and methods

    Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases.

    Results

    A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification.

    Conclusions

    We propose new potential protein biomarker candidates for classifying WD-SI-NET at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NET and their eventual use in diagnostics.

    Fulltekst (pdf)
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  • 7.
    Giandomenico, V
    et al.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Boccherini, M.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ Hosp, Uppsala, Sweden..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ Hosp, Uppsala, Sweden..
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Paganelli, G.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    miR-196a Is Specifically Regulated in FDG-PET Positive and Negative Small Intestinal Neuroendocrine Tumor Patients at Late Stage of Disease2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 115-115Artikkel i tidsskrift (Fagfellevurdert)
  • 8.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Small Intestinal Neuroendocrine Tumor Analyses: Somatostatin Analog Effects and MicroRNA Profiling2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) originate from serotonin-producing enterochromaffin (EC) cells in the intestinal mucosa. Somatostatin analogs (SSAs) are mainly used to control hormonal secretion and tumor growth. However, the molecular mechanisms leading to the control of SI-NETs are unknown. Although microRNAs (miRNAs) are post transcriptional regulators deeply studied in many cancers, are not well-defined in SI-NETs. We adopted a two-pronged strategy to investigate SSAs and miRNAs: first, to provide novel insights into how SSAs control NET cells, and second, to identify an exclusive SI-NET miRNA expression, and investigate the biological functions of miRNA targets.

    To accomplish the first aim, we treated CNDT2.5 cells with octreotide for 16 months. Affymetrix microarray was performed to study gene variation of CNDT2.5 cells in the presence or absence of octreotide. The study revealed that octreotide induces six genes, ANXA1, ARHGAP18, EMP1, GDF15, TGFBR2 and TNFSF15.

    To accomplish the second aim, SI-NET tissue specimens were used to run genome-wide Affymetrix miRNA arrays. The expression of five miRNAs (miR-96, -182, -183, -196a and -200a) was significantly upregulated in laser capture microdissected (LCM) tumor cells versus LCM normal EC cells, whereas the expression of four miRNAs (miR-31, -129-5p, -133a and -215) was significantly downregulated in LCM tumor cells. We also detected nine tissue miRNAs in serum samples, showing that the expression of five miRNAs is significantly increased in SSA treated patients versus untreated patients. Conversely, SSAs do not change miRNA expression of four low expressed miRNAs. Silencing miR-196a expression was used to investigate functional activities in NET cells. This experimental approach showed that four miR-196a target genes, HOXA9, HOXB7, LRP4 and RSPO2, are significantly upregulated in silenced miR-196a NET cells.

    In conclusion, ANXA1, ARHGAP18, EMP1, GDF15, TGFBR2 and TNFSF15 genes might regulate cell growth and differentiation in NET cells, and play a role in an innovative octreotide signaling pathway. The global SI-NET miRNA profiling revealed that nine selected miRNAs might be involved in tumorigenesis, and play a potential role as novel markers for follow-up. Indeed, silencing miR-196a demonstrated that HOXA9, HOXB7, LRP4 and RSPO2 genes are upregulated at both transcriptional and translational levels.

    Delarbeid
    1. The Somatostatin Analogue Octreotide Inhibits Growth of Small Intestine Neuroendocrine Tumour Cells
    Åpne denne publikasjonen i ny fane eller vindu >>The Somatostatin Analogue Octreotide Inhibits Growth of Small Intestine Neuroendocrine Tumour Cells
    Vise andre…
    2012 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 10, s. e48411-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Octreotide is a widely used synthetic somatostatin analogue that significantly improves the management of neuroendocrine tumours (NETs). Octreotide acts through somatostatin receptors (SSTRs). However, the molecular mechanisms leading to successful disease control or symptom management, especially when SSTRs levels are low, are largely unknown. We provide novel insights into how octreotide controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with octreotide and then were profiled using Affymetrix microarray analysis. Quantitative real-time PCR and western blot analyses were used to validate microarray profiling in silico data. WST-1 cell proliferation assay was applied to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 μM octreotide at different time points. Moreover, laser capture microdissected tumour cells and paraffin embedded tissue slides from SI-NETs at different stages of disease were used to identify transcriptional and translational expression. Microarrays analyses did not reveal relevant changes in SSTR expression levels. Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15 (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at transcript and protein levels. We suggest that octreotide may use a potential novel framework to exert its beneficial effect as a drug and to convey its action on neuroendocrine cells. Thus, six novel genes may regulate cell growth and differentiation in normal and tumour neuroendocrine cells and have a role in a novel octreotide mechanism system.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-186023 (URN)10.1371/journal.pone.0048411 (DOI)000310600500127 ()
    Tilgjengelig fra: 2012-11-29 Laget: 2012-11-27 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.
    Åpne denne publikasjonen i ny fane eller vindu >>Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.
    Vise andre…
    2013 (engelsk)Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, nr 5, s. 685-696Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Well-differentiated small intestinal neuroendocrine tumors are rare malignancies. They arise from enterochromaffin cells and very little is known about differential microRNA (miRNA) expression. The aim of this study was to identify the miRNA profile of well-differentiated small intestinal neuroendocrine tumors, which may have a critical role in tumor development, progression and potentially develop miRNAs as novel clinical biomarkers. Specimens from two test groups, 24 small intestinal neuroendocrine tumor specimens at different stages of malignancy, are included in this study. Total RNA from the first test group, five primary tumors, five mesentery metastases and five liver metastases was hybridized onto the Affymetrix Genechip miRNA arrays to perform a genome-wide profile. The results were validated by using quantitative real-time PCR (QRT-PCR) and northern blot analyses. We then expanded the investigation to laser capture microdissected small intestinal neuroendocrine tumor cells and immuno-laser capture microdissected normal enterochromaffin cells of the first test group. Furthermore, a second test group, three primary tumors, three mesentery metastases and three liver metastases, was included in the study. Thus, two independent test groups validated the data by QRT-PCR. Moreover, we characterized nine miRNAs, five (miR-96, -182, -183, -196a and -200a), which are upregulated during tumor progression, whereas four (miR-31, -129-5p, -133a and -215) are downregulated. Several online software programs were used to predict potential miRNA target genes to map a number of putative target genes for the aberrantly regulated miRNAs, through an advanced and novel bioinformatics analysis. Our findings provide information about pivotal miRNAs, which may lead to further insights into tumorigenesis, progression mechanisms and novel therapeutic targets recognition.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-194041 (URN)10.1038/modpathol.2012.216 (DOI)000318456200008 ()23328977 (PubMedID)
    Tilgjengelig fra: 2013-02-07 Laget: 2013-02-07 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3. Circulating microRNA detection in small intestinal neuroendocrine tumor patients treated with somatostatin analogs
    Åpne denne publikasjonen i ny fane eller vindu >>Circulating microRNA detection in small intestinal neuroendocrine tumor patients treated with somatostatin analogs
    Vise andre…
    2014 (engelsk)Artikkel i tidsskrift, Meeting abstract (Fagfellevurdert) Submitted
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-233202 (URN)
    Tilgjengelig fra: 2014-09-30 Laget: 2014-09-30 Sist oppdatert: 2018-01-11bibliografisk kontrollert
    4. Functional role of miR-196a in neuroendocrine tumor cells
    Åpne denne publikasjonen i ny fane eller vindu >>Functional role of miR-196a in neuroendocrine tumor cells
    Vise andre…
    2015 (engelsk)Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, nr 1-2, s. 87-87Artikkel i tidsskrift, Meeting abstract (Fagfellevurdert) Published
    sted, utgiver, år, opplag, sider
    S. Karger, 2015
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-233206 (URN)10.1159/000431385 (DOI)000361683500030 ()
    Eksternt samarbeid:
    Konferanse
    12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Barcelona, SPAIN, MAR 11-13, 2015
    Tilgjengelig fra: 2014-09-30 Laget: 2014-09-30 Sist oppdatert: 2018-01-11bibliografisk kontrollert
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  • 9.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Essaghir, Ahmed
    Martijn, Cécile
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Lloyd, Ricardo V
    Demoulin, Jean-Baptiste
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.2013Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, nr 5, s. 685-696Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Well-differentiated small intestinal neuroendocrine tumors are rare malignancies. They arise from enterochromaffin cells and very little is known about differential microRNA (miRNA) expression. The aim of this study was to identify the miRNA profile of well-differentiated small intestinal neuroendocrine tumors, which may have a critical role in tumor development, progression and potentially develop miRNAs as novel clinical biomarkers. Specimens from two test groups, 24 small intestinal neuroendocrine tumor specimens at different stages of malignancy, are included in this study. Total RNA from the first test group, five primary tumors, five mesentery metastases and five liver metastases was hybridized onto the Affymetrix Genechip miRNA arrays to perform a genome-wide profile. The results were validated by using quantitative real-time PCR (QRT-PCR) and northern blot analyses. We then expanded the investigation to laser capture microdissected small intestinal neuroendocrine tumor cells and immuno-laser capture microdissected normal enterochromaffin cells of the first test group. Furthermore, a second test group, three primary tumors, three mesentery metastases and three liver metastases, was included in the study. Thus, two independent test groups validated the data by QRT-PCR. Moreover, we characterized nine miRNAs, five (miR-96, -182, -183, -196a and -200a), which are upregulated during tumor progression, whereas four (miR-31, -129-5p, -133a and -215) are downregulated. Several online software programs were used to predict potential miRNA target genes to map a number of putative target genes for the aberrantly regulated miRNAs, through an advanced and novel bioinformatics analysis. Our findings provide information about pivotal miRNAs, which may lead to further insights into tumorigenesis, progression mechanisms and novel therapeutic targets recognition.

  • 10.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Khan, M. S.
    Caplin, M.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Meyer, T.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    MicroRNA Expression in Serum of Small Intestine Neuroendocrine Tumor Patients and miR-196a Biological Function in Neuroendocrine Tumor Cells2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, nr 3-4, s. 228-228Artikkel i tidsskrift (Annet vitenskapelig)
  • 11.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Khan, Mohid
    Caplin, Martyn
    Meyer, Tim
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Circulating microRNA detection in small intestinal neuroendocrine tumor patients treated with somatostatin analogs2014Artikkel i tidsskrift (Fagfellevurdert)
  • 12.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Khan, Mohid
    Caplin, Martyn
    Meyer, Tim
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikkel-id e0125553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression.

    Fulltekst (pdf)
    fulltext
  • 13.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Martijn, Cecile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Essaghir, Ahmed
    Lloyd, Ricardo V.
    Demoulin, Jean-Baptiste
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    B12Global MicroRNA Profiling of Small Intestine Neuroendocrine Tumors (SI-NETs) and Establishment of a Method to Study Serum MicroRNA Expression From the Same Tumors2013Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, nr 2, s. 377-377Artikkel i tidsskrift (Annet vitenskapelig)
  • 14.
    Li, Su-Chen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Martijn, Cécile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cui, Tao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Essaghir, Ahmed
    Luque, Raúl M.
    Demoulin, Jean-Baptiste
    Castaño, Justo P.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    The Somatostatin Analogue Octreotide Inhibits Growth of Small Intestine Neuroendocrine Tumour Cells2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 10, s. e48411-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Octreotide is a widely used synthetic somatostatin analogue that significantly improves the management of neuroendocrine tumours (NETs). Octreotide acts through somatostatin receptors (SSTRs). However, the molecular mechanisms leading to successful disease control or symptom management, especially when SSTRs levels are low, are largely unknown. We provide novel insights into how octreotide controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with octreotide and then were profiled using Affymetrix microarray analysis. Quantitative real-time PCR and western blot analyses were used to validate microarray profiling in silico data. WST-1 cell proliferation assay was applied to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 μM octreotide at different time points. Moreover, laser capture microdissected tumour cells and paraffin embedded tissue slides from SI-NETs at different stages of disease were used to identify transcriptional and translational expression. Microarrays analyses did not reveal relevant changes in SSTR expression levels. Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15 (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at transcript and protein levels. We suggest that octreotide may use a potential novel framework to exert its beneficial effect as a drug and to convey its action on neuroendocrine cells. Thus, six novel genes may regulate cell growth and differentiation in normal and tumour neuroendocrine cells and have a role in a novel octreotide mechanism system.

    Fulltekst (pdf)
    fulltext
  • 15.
    Monazzam, Azita
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lau, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Razmara, Masoud
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Rosenström, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 748Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.

    Fulltekst (pdf)
    fulltext
  • 16.
    Shi, Hao
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Khan, Mohid
    Royal Free Hosp, London NW3 2QG, England.
    Caplin, Martyn
    Royal Free Hosp, London NW3 2QG, England.
    Meyer, Tim
    UCL, Inst Canc, London, England.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Functional role of miR-196a in neuroendocrine tumor cells2015Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, nr 1-2, s. 87-87Artikkel i tidsskrift (Fagfellevurdert)
1 - 16 of 16
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