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BETA
Nilsson, R. Jonas A.
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Publications (10 of 28) Show all publications
Tjon-Kon-Fat, L.-A., Sol, N., Wurdinger, T. & Nilsson, R. J. (2018). Platelet RNA in Cancer Diagnostics. Seminars in Thrombosis and Hemostasis, 44(2), 135-141
Open this publication in new window or tab >>Platelet RNA in Cancer Diagnostics
2018 (English)In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 44, no 2, p. 135-141Article in journal (Refereed) Published
Abstract [en]

Platelets are involved in several steps of cancer metastasis. During this process, platelets are exposed to the tumor and its environment, thereby exchanging biomolecules with the tumor cells and resulting in tumor-mediated education of the platelets and a change in their RNA profile. Analysis of platelet RNA profiles or direct measurement of tumor-derived biomarkers within platelets can provide information on ongoing cancer-related processes in the individual (e.g., whether the patient has cancer, the tumor type, and possibly identify oncogenic alterations driving the disease for treatment selection). The close interaction with the disease process and the ability to respond to systemic alterations make platelets an interesting biosource for implementation in precision medicine.

Place, publisher, year, edition, pages
THIEME MEDICAL PUBL INC, 2018
Keywords
platelets, biomarkers, liquid biopsy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145772 (URN)10.1055/s-0037-1606182 (DOI)000426118100007 ()28905353 (PubMedID)2-s2.0-85029755219 (Scopus ID)
Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2018-06-18Bibliographically approved
Tjon-Kon-Fat, L.-A., Lundholm, M., Schröder, M., Wurdinger, T., Thellenberg-Karlsson, C., Widmark, A., . . . Nilsson, R. J. (2018). Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients. The Prostate, 78(1), 48-53
Open this publication in new window or tab >>Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients
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2018 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
biomarkers, liquid biopsy, personalized medicine, platelet, prostate cancer, therapy stratification
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-142384 (URN)10.1002/pros.23443 (DOI)000417131400007 ()29094381 (PubMedID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-06-09Bibliographically approved
Köhn, L., Johansson, M., Grankvist, K. & Nilsson, J. (2017). Liquid biopsies in lung cancer: time to implement research technologies in routine care?. Annals of Translational Medicine, 5(13), Article ID 278.
Open this publication in new window or tab >>Liquid biopsies in lung cancer: time to implement research technologies in routine care?
2017 (English)In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 5, no 13, article id 278Article, review/survey (Refereed) Published
Abstract [en]

Lung cancer is the leading cause of cancer mortality. A substantial progress in the understanding of lung cancer biology has resulted in several promising targeted therapies for advanced disease. Druggable targets today include point mutations such as EGFR, BRAF and re-arrangements in genes such as ALK and ROS1. Liquid biopsies collecting e.g., circulating tumor DNA (ctDNA) reflects overall tumor information and is not biased by analyzing of only a small fraction of the tumor and is always accessible in contrast to the lung cancer tissue. Technological advances in detection of low frequency mutation variants in ctDNA have made it the dominating liquid biopsy platform in terms of utility and sensitivity. Circulating DNA or RNA may possible be used to define populations with higher risk of developing lung cancer, thus reducing screening cohorts and increasing the positive predictive value of screening. Blood based-tests may also aid to identify genetic alterations several weeks prior to radiologically verified recurrence and may be of great value in the follow-up of lung cancer patients. Besides being an alternative to invasive biopsies in selected cases, liquid biopsies offer a unique possibility to monitor treatment response following medical treatment as well as treatment response and resistance development after targeted therapy, giving a possibility to modify the treatment after the genetic profile of the tumor. Ideally, genetic alterations found in ctDNA could be tracked in real-time discriminating between fast-growing life-threatening tumors from more indolent slow growing tumors or premalignant growth that are of no concern for the wellbeing of the patient. This review focuses on future perspectives of liquid biopsies in lung cancer care for different clinical settings and present current technological platforms for further discussion of possible strategies for implementation of liquid biopsies in lung cancer.

Place, publisher, year, edition, pages
AME Publishing Company, 2017
Keywords
cell-free DNA, liquid biopsy, lung cancer, next-generation sequencing, personalized medicine
National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-139154 (URN)10.21037/atm.2017.04.12 (DOI)000408647900011 ()28758104 (PubMedID)
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2019-06-12Bibliographically approved
Best, M. G., Sol, N., 't Veld, S. G. J., Vancura, A., Muller, M., Niemeijer, A.-L. N., . . . Wurdinger, T. (2017). Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets. Cancer Cell, 32(2), 238-252
Open this publication in new window or tab >>Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
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2017 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 32, no 2, p. 238-252Article in journal (Refereed) Published
Abstract [en]

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142881 (URN)10.1016/j.ccell.2017.07.004 (DOI)000407932500010 ()28810146 (PubMedID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2018-06-09Bibliographically approved
Holgersson, G., Bergström, S., Hallqvist, A., Liv, P., Nilsson, R. J., Willén, L., . . . Bergqvist, M. (2017). The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy. Neoplasma (Bratislava), 64(6), 909-915
Open this publication in new window or tab >>The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
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2017 (English)In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 64, no 6, p. 909-915Article in journal (Refereed) Published
Abstract [en]

Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting

Place, publisher, year, edition, pages
Bratislava: AEPress, 2017
Keywords
NSCLC, anemia, leukocytosis, thrombocytosis, prognostic, survival
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-159535 (URN)10.4149/neo_2017_614 (DOI)000418756500013 ()28895417 (PubMedID)
Available from: 2019-05-30 Created: 2019-05-30 Last updated: 2019-06-19Bibliographically approved
Bijnsdorp, I. V., Hodzic, J., Lagerweij, T., Westerman, B., Krijgsman, O., Broeke, J., . . . Geldof, A. A. (2016). miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110. OncoTarget, 7(13), 16676-16687
Open this publication in new window or tab >>miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 13, p. 16676-16687Article in journal (Refereed) Published
Abstract [en]

The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

Keywords
prostate cancer, centrosome, CP110, miR-129-3p, metastasis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-121485 (URN)10.18632/oncotarget.7572 (DOI)000375692900105 ()26918338 (PubMedID)
Available from: 2016-06-17 Created: 2016-06-02 Last updated: 2018-06-07Bibliographically approved
Nilsson, R. J., Karachaliou, N., Berenguer, J., Gimenez-Capitan, A., Schellen, P., Teixido, C., . . . Wurdinger, T. (2016). Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. OncoTarget, 7(1), 1066-1075
Open this publication in new window or tab >>Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 1, p. 1066-1075Article in journal (Refereed) Published
Abstract [en]

Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.

Keywords
diagnostics, NSCLC, liquid biopsies, platelets, EML4-ALK
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-117842 (URN)10.18632/oncotarget.6279 (DOI)000369950300077 ()26544515 (PubMedID)
Available from: 2016-03-30 Created: 2016-03-04 Last updated: 2018-06-07Bibliographically approved
Best, M., Sol, N., Kooi, I., Nilsson, J., Westerman, B., Ylstra, B., . . . Wurdinger, T. (2015). Allowance of tumor-educated platelets for multiclass liquid biopsy-based diagnosis of cancer. Journal of Clinical Oncology, 33(15, suppl.), Article ID 11058.
Open this publication in new window or tab >>Allowance of tumor-educated platelets for multiclass liquid biopsy-based diagnosis of cancer
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2015 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15, suppl., article id 11058Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Society of Clinical Oncology, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-107311 (URN)000358036900317 ()
Available from: 2015-08-24 Created: 2015-08-21 Last updated: 2018-06-07Bibliographically approved
Best, M. G., Sol, N., Kooi, I., Tannous, J., Westerman, B. A., Rustenburg, F., . . . Wurdinger, T. (2015). RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell, 28(5), 666-676
Open this publication in new window or tab >>RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics
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2015 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 28, no 5, p. 666-676Article in journal (Refereed) Published
Abstract [en]

Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".

National Category
Cancer and Oncology Cell Biology
Identifiers
urn:nbn:se:umu:diva-112248 (URN)10.1016/j.ccell.2015.09.018 (DOI)000364609100014 ()26525104 (PubMedID)
Available from: 2015-12-08 Created: 2015-12-04 Last updated: 2018-06-07Bibliographically approved
Best, M., Sol, N., Kooi, I., Nilsson, J., Westerman, B., Yistra, B., . . . Wurdinger, T. (2015). Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer. Paper presented at 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR), APR 18-22, 2015, Philadelphia, PA. Cancer Research, 75(Suppl. 15), Article ID LB-124.
Open this publication in new window or tab >>Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer
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2015 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no Suppl. 15, article id LB-124Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Association for Cancer Research, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-119094 (URN)10.1158/1538-7445.AM2015-LB-124 (DOI)000371597100226 ()
Conference
106th Annual Meeting of the American-Association-for-Cancer-Research (AACR), APR 18-22, 2015, Philadelphia, PA
Available from: 2016-04-13 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
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