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Grimelius, Lars
Alternative names
Publications (10 of 33) Show all publications
Grimelius, L. & Åkerström, G. (2017). Biographical item: "Henry Johansson in memoriam" in Upsala Journal Of Medical Sciences, vol 122, Issue: 4, pp 260-261. , 122(4)
Open this publication in new window or tab >>Biographical item: "Henry Johansson in memoriam" in Upsala Journal Of Medical Sciences, vol 122, Issue: 4, pp 260-261
2017 (English)Other (Other (popular science, discussion, etc.))
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-350222 (URN)10.1080/03009734.2017.1396271 (DOI)000423294800009 ()29338500 (PubMedID)
Note

Minnesord (Obituary)

WoS title: Henry Johansson in memoriam OBITUARY

Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-05-18Bibliographically approved
Ali, A. S., Grönberg, M., Federspiel, B., Scoazec, J.-Y., Hjortland, G. O., Gronbaek, H., . . . Tiensuu Janson, E. (2017). Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma. PLoS ONE, 12(11), Article ID e0187667.
Open this publication in new window or tab >>Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0187667Article in journal (Refereed) Published
Abstract [en]

Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-341933 (URN)10.1371/journal.pone.0187667 (DOI)000414572100031 ()29112960 (PubMedID)
Funder
Swedish Cancer Society, CAN558/2014
Available from: 2018-02-16 Created: 2018-02-16 Last updated: 2018-07-13Bibliographically approved
Antonodimitrakis, P. C., Olofsson, H., Grimelius, L., Sundin, A., Wassberg, C., Granberg, D., . . . Eriksson, B. (2017). Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study. International Journal of Endocrine Oncology, 4(1), 9-22
Open this publication in new window or tab >>Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study
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2017 (English)In: International Journal of Endocrine Oncology, Vol. 4, no 1, p. 9-22Article in journal (Refereed) Published
Abstract [en]

Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

Keywords
chemotherapy, IFN-α, neuroendocrine tumors, pancreas, somatostatin analogs, survival, vasoactive intestinal polypeptide
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-342674 (URN)10.2217/ije-2016-0012 (DOI)000426222300003 ()
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-03-23Bibliographically approved
Alit, A., Grönberg, M., Federspiel, B., Hjortland, G. O., Ladekarl, M., Langer, S. W., . . . Tiensuu Janson, E. (2016). Expression of Mutated p53 Protein in Gastroenteropancreatic Neuroendocrine Carcinoma (WHO G3). Paper presented at 13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 09-11, 2016, Barcelona, SPAIN. Neuroendocrinology, 103, 43-43
Open this publication in new window or tab >>Expression of Mutated p53 Protein in Gastroenteropancreatic Neuroendocrine Carcinoma (WHO G3)
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2016 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, p. 43-43Article in journal, Meeting abstract (Refereed) Published
Keywords
Neuroendocrine carcinoma, Mutation, p53, Overall survival
National Category
Cancer and Oncology Neurology
Identifiers
urn:nbn:se:uu:diva-313701 (URN)000386481600115 ()
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: 2018-07-13Bibliographically approved
Tsolakis, A. V., Grimelius, L., Granerus, G., Stridsberg, M., Falkmer, S. E. & Janson, E. T. (2015). Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours. World Journal of Gastroenterology, 21(47), 13240-13249
Open this publication in new window or tab >>Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 47, p. 13240-13249Article in journal (Refereed) Published
Abstract [en]

AIM:

To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite.

METHODS:

Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients.

RESULTS:

In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms.

CONCLUSION:

Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

Keywords
Enterochromaffin-like cells, High performance liquid chromatography, Gastric neuroendocrine tumours, Histidine decarboxylase, Immunohistochemistry, Urinary excretion of the main histamine metabolite methylimidazoleacetic acid, Vesicular monoamine transporter 2
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-274442 (URN)10.3748/wjg.v21.i47.13240 (DOI)000366889600004 ()26715806 (PubMedID)
Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2017-11-30Bibliographically approved
Ahlgren, K. M., Fall, T., Landegren, N., Grimelius, L., von Euler, H., Sundberg, K., . . . Kämpe, O. (2014). Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus. PLoS ONE, 9(8), e105473
Open this publication in new window or tab >>Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e105473-Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS:

Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

METHODS:

Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.

RESULTS:

None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.

CONCLUSIONS/INTERPRETATIONS:

Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-232422 (URN)10.1371/journal.pone.0105473 (DOI)000340952200053 ()25153886 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2014-09-17 Created: 2014-09-17 Last updated: 2017-12-05Bibliographically approved
Grönberg, M., Tsolakis, A. V., Holmbäck, U., Stridsberg, M., Grimelius, L. & Janson, E. T. (2013). Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake. Neuroendocrinology, 97(4), 291-299
Open this publication in new window or tab >>Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake
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2013 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 97, no 4, p. 291-299Article in journal (Refereed) Published
Abstract [en]

Background:

Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs.

Materials and Methods:

The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs.

Results:

Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals.

Conclusion:

Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-188786 (URN)10.1159/000345366 (DOI)000320166900001 ()23147274 (PubMedID)
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06Bibliographically approved
Giandomenico, V., Cui, T., Grimelius, L., Öberg, K., Pelosi, G. & Tsolakis, A. V. (2013). Olfactory Receptor 51E1 as a Novel Target for Diagnosis in Somatostatin Receptor Negative Lung Carcinoids. Journal of Molecular Endocrinology, 51, 277-286
Open this publication in new window or tab >>Olfactory Receptor 51E1 as a Novel Target for Diagnosis in Somatostatin Receptor Negative Lung Carcinoids
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2013 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 51, p. 277-286Article in journal (Refereed) Published
Abstract [en]

Somatostatin receptors (SSTRs) may be used in lung carcinoids (LCs) for diagnosis and therapy, although additional targets are clearly warranted. This study aimed to investigate whether olfactory receptor 51E1 (OR51E1) may be a potential target for LCs. OR51E1 coding sequence was analyzed in LC cell lines, NCI-H727 and NCI-H720. OR51E1 transcript expression was investigated in LC cell lines and frozen specimens by quantitative real-time PCR. OR51E1, SSTR2, SSTR3, and SSTR5 expression was evaluated by immunohistochemistry on paraffin-embedded sections of 73 typical carcinoids (TCs), 14 atypical carcinoids (ACs) and 11 regional/distant metastases, and compared to OctreoScan data. Immunohistochemistry results were rendered semiquantitatively on a scale from 0 to 3+, taking into account the cellular compartmentalization (membrane vs. cytoplasm) and the percentage of tumor cells (<50% vs. >50%). Our results showed that wild-type OR51E1 transcript was expressed in both LC cell lines. OR51E1 mRNA was expressed in 9/12 TCs and 7/9 ACs (p=NS). Immunohistochemically, OR51E1, SSTR2, SSTR3 and SSTR5 were detected in 85%, 71%, 25% and 39% of TCs, and in 86%, 79%, 43% and 36% of ACs, respectively. OR51E1 immunohistochemical scores were higher or equal compared to SSTRs in 79% of TCs and 86% of ACs. Furthermore, in the LC cases where all SSTR subtypes were lacking, membrane OR51E1 expression was detected in 10/17 TCs and 1/2 ACs. Moreover, higher OR51E1 immunohistochemical scores were detected in 5/6 OctreoScan-negative LC lesions. Therefore, the high expression of OR51E1 in LCs makes it a potential novel diagnostic target in SSTR-negative tumors.

Keywords
Olfactory receptor 51E1, lung carcinoids, novel target for diagnosis, somatostatin receptors, OctreoScan
National Category
Cell and Molecular Biology Cancer and Oncology Endocrinology and Diabetes
Research subject
Endocrinology and Diabetology; Lung Medicine; Molecular Biology; Oncology
Identifiers
urn:nbn:se:uu:diva-205526 (URN)10.1530/JME-13-0144 (DOI)000329207100012 ()23969981 (PubMedID)
Note

De två första författarna delar första författarskapet.

Available from: 2013-08-29 Created: 2013-08-19 Last updated: 2018-01-11Bibliographically approved
Tsolakis, A. V., Grimelius, L. & Islam, M. S. (2012). Expression of the coiled coil domain containing protein 116 in the pancreatic islets and endocrine pancreatic tumors. Islets, 4(5), 349-353
Open this publication in new window or tab >>Expression of the coiled coil domain containing protein 116 in the pancreatic islets and endocrine pancreatic tumors
2012 (English)In: Islets, ISSN 1938-2022, Vol. 4, no 5, p. 349-353Article in journal (Refereed) Published
Abstract [en]

Aims: Coiled coil domain containing protein 116 (CCDC116) is a product of the gene coiled coil domain containing 116 located on human chromosome 22. Its function has not yet been established. The present study focuses on the expression of this protein in human pancreatic islets and in the endocrine pancreatic tumors (EPTs). Methods and Results: Expression of the protein was evaluated by immunohistochemistry in endocrine pancreas from six patients and in various EPTs from 51 patients. In pancreatic islets, virtually all insulin, approx. 75% of the somatostatin, and approx. 60% of the pancreatic polypeptide (PP) cells were immunoreactive for the CCDC116 protein whereas glucagon, ghrelin and the exocrine cells were not. All insulinomas, gastrinomas, non-functioning sporadic tumors and the hereditary multihormonal EPTs were immunoreactive with variable relative incidence. Two of the three somatostatinomas, and one of the three ACTH-secreting tumors also expressed CCDC116. Conclusions: The CCDC116 protein is expressed in all islet cell types except the glucagon and ghrelin cells. Most of the EPTs also contained CCDC116 protein. These findings suggest that this protein may play some role for the above mentioned endocrine cells and tumors. Its function has to be investigated in future studies.

National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-189888 (URN)10.4161/isl.22416 (DOI)000312209200005 ()23072936 (PubMedID)
Available from: 2013-01-04 Created: 2013-01-04 Last updated: 2013-01-16Bibliographically approved
Kanakis, G., Kaltsas, G., Granberg, D., Grimelius, L., Papaioannou, D., Tsolakis, A. V. & Öberg, K. (2012). Unusual Complication of a Pancreatic Neuroendocrine Tumor Presenting with Malignant Hypercalcemia. Journal of Clinical Endocrinology and Metabolism, 97(4), E627-E631
Open this publication in new window or tab >>Unusual Complication of a Pancreatic Neuroendocrine Tumor Presenting with Malignant Hypercalcemia
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2012 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 4, p. E627-E631Article in journal (Refereed) Published
Abstract [en]

Context:

Hypersecretion of PTHrP is a relatively common cause of malignancy-related hypercalcemia but has only been described in a few cases of neuroendocrine tumors (NET).

Objective:

The aim of this case report is to describe the clinical syndrome, complex therapeutic interventions, and unusual complications caused by persistent PTHrP hypersecretion in a patient with a pancreatic NET.

Case Illustration:

A 58-yr-old male patient presented with nonspecific abdominal pain and was found to have severe hypercalcemia secondary to a well-differentiated NET of the pancreas associated with extensive liver metastases. Elevated ionized calcium levels accompanied by low serum PTH and remarkably elevated PTHrP concentrations were consistent with PTHrP-related hypercalcemia that proved to be resistant to various chemotherapeutic regimens and supportive therapy. Partial control of the humoral syndrome was obtained only after the application of cytoreductive interventions and the introduction of various molecular targeted therapies. Due to persistent PTHrP action, bone disease emerged in the form of brown tumors.

Discussion:

The manifestation of paraneoplastic syndrome due to PTHrP hypersecretion, despite its rareness in NET, should be considered in the differential diagnosis of hypercalcemia in such tumors. Moreover, the appearance of bone lesions in this setting may be in the context of metabolic bone disease and could be misdiagnosed as bone metastases.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-168985 (URN)10.1210/jc.2011-2592 (DOI)000302787800016 ()22319031 (PubMedID)
Available from: 2012-02-21 Created: 2012-02-21 Last updated: 2017-12-07Bibliographically approved
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