uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Li, Su-Chen
Publications (10 of 16) Show all publications
Monazzam, A., Lau, J., Velikyan, I., Li, S.-C., Razmara, M., Rosenström, U., . . . Skogseid, B. (2018). Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET. Scientific Reports, 8, Article ID 748.
Open this publication in new window or tab >>Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 748Article in journal (Refereed) Published
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.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-342327 (URN)10.1038/s41598-017-18855-0 (DOI)000422637200007 ()29335487 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-28Bibliographically approved
Giandomenico, V., Li, S.-C., Lind, T., Boccherini, M., Skogseid, B., Eriksson, B., . . . Paganelli, G. (2016). miR-196a Is Specifically Regulated in FDG-PET Positive and Negative Small Intestinal Neuroendocrine Tumor Patients at Late Stage of Disease. Paper presented at 13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 09-11, 2016, Barcelona, SPAIN. Neuroendocrinology, 103, 115-115
Open this publication in new window or tab >>miR-196a Is Specifically Regulated in FDG-PET Positive and Negative Small Intestinal Neuroendocrine Tumor Patients at Late Stage of Disease
Show others...
2016 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, p. 115-115Article in journal, Meeting abstract (Refereed) Published
Keywords
Glycolytic metabolism, Peptide receptor radionuclide therapy (PRRT), Serum samples, miRNA, FDG-PET positive and -PET negative SI-NET patients
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-313706 (URN)000386481600301 ()
Conference
13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 09-11, 2016, Barcelona, SPAIN
Available from: 2017-01-23 Created: 2017-01-23 Last updated: 2017-04-24Bibliographically approved
Shi, H., Li, S.-C., Khan, M., Caplin, M., Meyer, T., Öberg, K. & Giandomenico, V. (2015). Functional role of miR-196a in neuroendocrine tumor cells. Paper presented at 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Barcelona, SPAIN, MAR 11-13, 2015. Neuroendocrinology, 102(1-2), 87-87
Open this publication in new window or tab >>Functional role of miR-196a in neuroendocrine tumor cells
Show others...
2015 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, no 1-2, p. 87-87Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
S. Karger, 2015
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-233206 (URN)10.1159/000431385 (DOI)000361683500030 ()
External cooperation:
Conference
12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Barcelona, SPAIN, MAR 11-13, 2015
Available from: 2014-09-30 Created: 2014-09-30 Last updated: 2018-01-11Bibliographically approved
Li, S.-C., Khan, M., Caplin, M., Meyer, T., Öberg, K. & Giandomenico, V. (2015). Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs. PLoS ONE, 10(5), Article ID e0125553.
Open this publication in new window or tab >>Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs
Show others...
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0125553Article in journal (Refereed) Published
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.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-255077 (URN)10.1371/journal.pone.0125553 (DOI)000353943400044 ()25942502 (PubMedID)
Available from: 2015-06-12 Created: 2015-06-12 Last updated: 2017-12-04Bibliographically approved
Li, S.-C., Khan, M., Caplin, M., Meyer, T., Öberg, K. & Giandomenico, V. (2014). Circulating microRNA detection in small intestinal neuroendocrine tumor patients treated with somatostatin analogs.
Open this publication in new window or tab >>Circulating microRNA detection in small intestinal neuroendocrine tumor patients treated with somatostatin analogs
Show others...
2014 (English)Article in journal, Meeting abstract (Refereed) Submitted
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:uu:diva-233202 (URN)
Available from: 2014-09-30 Created: 2014-09-30 Last updated: 2018-01-11Bibliographically approved
Li, S.-C., Khan, M. S., Caplin, M., Öberg, K., Meyer, T. & Giandomenico, V. (2014). MicroRNA Expression in Serum of Small Intestine Neuroendocrine Tumor Patients and miR-196a Biological Function in Neuroendocrine Tumor Cells. Paper presented at 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 05-07, 2014, Barcelona, SPAIN. Neuroendocrinology, 99(3-4), 228-228
Open this publication in new window or tab >>MicroRNA Expression in Serum of Small Intestine Neuroendocrine Tumor Patients and miR-196a Biological Function in Neuroendocrine Tumor Cells
Show others...
2014 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, no 3-4, p. 228-228Article in journal, Meeting abstract (Other academic) Published
Keywords
neuroendocrine tumors, serum mirna expression, mirna, target functions
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-237656 (URN)000343640100028 ()
Conference
11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 05-07, 2014, Barcelona, SPAIN
Available from: 2014-12-10 Created: 2014-12-03 Last updated: 2017-12-05Bibliographically approved
Li, S.-C. (2014). Small Intestinal Neuroendocrine Tumor Analyses: Somatostatin Analog Effects and MicroRNA Profiling. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Small Intestinal Neuroendocrine Tumor Analyses: Somatostatin Analog Effects and MicroRNA Profiling
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. p. 48
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1039
Keywords
Small intestinal neuroendocrine tumors, Somatostatin analogs, Laser-capture microdissection, Microarray profiling and microRNA profiling
National Category
Cell and Molecular Biology
Research subject
Biology with specialization in Molecular Biology
Identifiers
urn:nbn:se:uu:diva-233207 (URN)978-91-554-9058-4 (ISBN)
Public defence
2014-11-20, Enghoffsalen, Entrance 50, Uppsala University Hospital, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2014-10-30 Created: 2014-09-30 Last updated: 2018-01-11
Li, S.-C., Martijn, C., Essaghir, A., Lloyd, R. V., Demoulin, J.-B., Öberg, K. & Giandomenico, V. (2013). B12Global MicroRNA Profiling of Small Intestine Neuroendocrine Tumors (SI-NETs) and Establishment of a Method to Study Serum MicroRNA Expression From the Same Tumors. Paper presented at 5th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 11–13, 2012, San Diego, California. Pancreas, 42(2), 377-377
Open this publication in new window or tab >>B12Global MicroRNA Profiling of Small Intestine Neuroendocrine Tumors (SI-NETs) and Establishment of a Method to Study Serum MicroRNA Expression From the Same Tumors
Show others...
2013 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 2, p. 377-377Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-197217 (URN)000314975200065 ()
Conference
5th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 11–13, 2012, San Diego, California
Available from: 2013-03-19 Created: 2013-03-19 Last updated: 2017-12-06Bibliographically approved
Li, S.-C., Essaghir, A., Martijn, C., Lloyd, R. V., Demoulin, J.-B., Öberg, K. & Giandomenico, V. (2013). Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.. Modern Pathology, 26(5), 685-696
Open this publication in new window or tab >>Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors.
Show others...
2013 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, no 5, p. 685-696Article in journal (Refereed) 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.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-194041 (URN)10.1038/modpathol.2012.216 (DOI)000318456200008 ()23328977 (PubMedID)
Available from: 2013-02-07 Created: 2013-02-07 Last updated: 2017-12-06Bibliographically approved
Darmanis, S., Cui, T., Drobin, K., Li, S.-C., Öberg, K., Nilsson, P., . . . Giandomenico, V. (2013). Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors. PLoS ONE, 8(11), e81712
Open this publication in new window or tab >>Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e81712-Article in journal (Refereed) Published
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.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology Cancer and Oncology Endocrinology and Diabetes Gastroenterology and Hepatology
Research subject
Endocrinology and Diabetology; Molecular Biology; Molecular Biotechnology; Oncology
Identifiers
urn:nbn:se:uu:diva-205549 (URN)10.1371/journal.pone.0081712 (DOI)000327543500120 ()
Available from: 2013-08-29 Created: 2013-08-19 Last updated: 2018-01-11Bibliographically approved
Organisations

Search in DiVA

Show all publications