U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden

Glimelius, Bengt; Melin, Beatrice; Enblad, Gunilla; Alafuzoff, Irina; Beskow, Anna H.; Åhlström, Håkan; Bill‐Axelson, Anna; Birgisson, Helgi; Björ, Ove; Edqvist, Per‐Henrik; Hansson, Tomas; Helleday, Thomas; Hellman, Per; Henriksson, Kerstin; Hesselager, Göran; Hultdin, Magnus; Häggman, Michael; Höglund, Martin; Jonsson, Håkan; Larsson, Chatarina; Lindman, Henrik; Ljuslinder, Ingrid; Mindus, Stéphanie; Nygren, Peter; Pontén, Fredrik; Riklund, Katrine; Rosenquist, Richard; Sandin, Fredrik; Schwenk, Jochen M.; Stenling, Roger; Stålberg, Karin; Stålberg, Peter; Sundström, Christer; Karlsson, Camilla; Westermark, Bengt; Bergh, Anders; Claesson‐Welsh, Lena; Palmqvist, Richard; Sjöblom, Tobias

doi:10.1080/0284186x.2017.1337926

Cited by 74 publications

(58 citation statements)

References 14 publications

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“…7a). We next evaluated expression in a panel of prostate cancer patient samples from the U-CAN resource [20]. The cohort for this study consisted of 85 men (mean age 67.18) who had undergone a radical prostatectomy.…”

Section: Fasn Rhou and Cdc42 Expression Is Increased In High Gleasonmentioning

confidence: 99%

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Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

et al. 2020

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Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

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Section: Fasn Rhou and Cdc42 Expression Is Increased In High Gleasonmentioning

confidence: 99%

“…Prostate cancer tissues were obtained through the U-CAN project (www.u-can.uu.se) [20]. The tissue microarray (TMA) cohort was constructed from formalin fixed paraffin embedded tumours as previously described [26].…”

Section: Immunohistochemistrymentioning

confidence: 99%

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

et al. 2020

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“…For a subgroup of patients, included in the biobank cohort 2005-2015, we have collected clinical data in order to describe the cohort in detail. Inclusion in the biobank is prospective and patients included in the biobank cohort after 2010 is participating in the Uppsala-Umeå comprehensive cancer consortium (U-CAN), which is a joint project with Uppsala University [22].…”

Section: Introductionmentioning

confidence: 99%

Improved treatment of glioblastoma – changes in survival over two decades at a single regional Centre

et al. 2019

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Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center. Patients and methods: Survival was studied for 571 patients in our region diagnosed with GBM between 1995 and 2015. Samples from 244 patients out of those treated 2005-2015 have been included in a tissue/blood bank and a clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment. Results: The median OS for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995-1996 and 2010-2015, respectively (p < .05). The 2-year survival for the same time periods improved from 7% to 18% (p < .01). After introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased OS was noted and following implementation of intraoperative 5-aminolevulinic acid the number of tumor resection !95% did increase from 33% to 54% (p < .001). Positive prognostic factors for survival were young age, good performance status, absence of inflammatory disease, absence of diabetes or metabolic disease, tumor resection !95%, and completion of postoperative radiochemotherapy. Discussion: The results of this study are consistent with earlier results regarding survival and prognostic factors and confirm results from randomized controlled trials in a clinical setting. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.

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“…Patients included in the study were from the Uppsala-Umeå Comprehensive Cancer Consortium (U-CAN) project [60]. Tissue specimens were collected from patients who had been surgically resected for CRC at the Department of Surgery, Umeå University Hospital, Sweden since 2010.…”

Section: Study Population Of Patients With Crcmentioning

confidence: 99%

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Larsson

Ljuslinder

et al. 2020

Cancers

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Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.

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U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden

Cited by 74 publications

References 14 publications

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Improved treatment of glioblastoma – changes in survival over two decades at a single regional Centre

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

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