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  1. Article: Mouse Models of Congenital Kidney Anomalies.

    Kuure, Satu / Sariola, Hannu

    Advances in experimental medicine and biology

    2020  Volume 1236, Page(s) 109–136

    Abstract: Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects, which cause the majority of chronic kidney diseases in children. CAKUT covers a wide range of malformations that derive from deficiencies in embryonic kidney and lower ...

    Abstract Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects, which cause the majority of chronic kidney diseases in children. CAKUT covers a wide range of malformations that derive from deficiencies in embryonic kidney and lower urinary tract development, including renal aplasia, hypodysplasia, hypoplasia, ectopia, and different forms of ureter abnormalities. The majority of the genetic causes of CAKUT remain unknown. Research on mutant mice has identified multiple genes that critically regulate renal differentiation. The data generated from this research have served as an excellent resource to identify the genetic bases of human kidney defects and have led to significantly improved diagnostics. Furthermore, genetic data from human CAKUT studies have also revealed novel genes regulating kidney differentiation.
    MeSH term(s) Animals ; Chronic Disease ; Disease Models, Animal ; Humans ; Kidney/abnormalities ; Kidney Diseases/congenital ; Kidney Diseases/diagnosis ; Kidney Diseases/genetics ; Mice ; Urinary Tract/abnormalities
    Language English
    Publishing date 2020-04-17
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-15-2389-2_5
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  2. Book ; Thesis: Angiogenesis of the kidney

    Sariola, Hannu

    1984  

    Size 40 S. : Ill., graph. Darst.
    Publishing country Finland
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Helsinki, Univ., Diss., 1984
    HBZ-ID HT003069693
    ISBN 951-99609-8-8 ; 978-951-99609-8-2
    Database Catalogue ZB MED Medicine, Health

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  3. Article ; Online: HLA-G expression correlates with histological grade but not with prognosis in colorectal carcinoma.

    Kaprio, Tuomas / Sariola, Hannu / Linder, Nina / Lundin, Johan / Kere, Juha / Haglund, Caj / Wedenoja, Satu

    HLA

    2021  Volume 98, Issue 3, Page(s) 213–217

    Abstract: Trophoblast-specific expression of HLA-G induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal ... ...

    Abstract Trophoblast-specific expression of HLA-G induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p = 0.002) and non-mucinous histology (p = 0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7%-75.0%) compared to 74.8% (95% CI: 63.2%-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC.
    MeSH term(s) Alleles ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; HLA-G Antigens/genetics ; Humans ; Prognosis ; Trophoblasts
    Chemical Substances HLA-G Antigens
    Language English
    Publishing date 2021-06-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.14334
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  4. Article: STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells.

    Murumägi, Astrid / Ungureanu, Daniela / Arjama, Mariliina / Bützow, Ralf / Lohi, Jouko / Sariola, Hannu / Kanerva, Jukka / Koskenvuo, Minna / Kallioniemi, Olli

    Translational oncology

    2021  Volume 14, Issue 4, Page(s) 101027

    Abstract: Genetic rearrangements involving the anaplastic lymphoma kinase (ALK) gene create oncogenic drivers for several cancers, including malignant peritoneal mesothelioma (MPeM). Here, we report genomic and functional precision oncology profiling on a rare ... ...

    Abstract Genetic rearrangements involving the anaplastic lymphoma kinase (ALK) gene create oncogenic drivers for several cancers, including malignant peritoneal mesothelioma (MPeM). Here, we report genomic and functional precision oncology profiling on a rare case of a 5-year old patient diagnosed with wide-spread and aggressive MPeM, driven by STRN-ALK rearrangement. We established genomically representative patient-derived cancer cells (PDCs) from the tumor sample and performed high-throughput drug sensitivity testing with 527 oncology compounds to identify potent inhibitors. As expected, the PDCs were overall sensitive to the ALK inhibitors, although the eight different inhibitors tested had variable efficacy. We also discovered other effective inhibitors, such as MEK/ERK inhibitors and those targeting pathways downstream of ALK as well as Bcl-xl inhibitors. In contrast, most cytotoxic drugs were not very effective. ALK inhibitors synergized with MEK and PI3K/mTOR inhibitors, highlighting potential combinatorial strategies to enhance drug efficacy and tackle drug resistance. Based on genomic data and associated functional validation, the patient was treated with the ALK inhibitor crizotinib in combination with conventional chemotherapy (cisplatin and gemcitabine). A complete disease remission was reached, lasting now for over 3 years. Our results illustrate a rare pediatric cancer case, and highlight the potential of functional precision oncology to discover pathogenetic drivers, validate dependency on driver signals, compare different inhibitors against each other and potentially enhance targeted treatments by drug combinations. Such real-time implementation of functional precision oncology could pave the way towards safer and more effective personalized cancer therapies for individual pediatric cancer patients with rare tumors.
    Language English
    Publishing date 2021-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233
    ISSN 1936-5233
    DOI 10.1016/j.tranon.2021.101027
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  5. Article: Ihmisyysgeenit--apinoiden raivo, rauha ja aivot.

    Sariola, Hannu

    Duodecim; laaketieteellinen aikakauskirja

    2004  Volume 120, Issue 15, Page(s) 1836–1837

    Title translation Genes behind humanity, rage, peace and the brain of apes.
    MeSH term(s) Animals ; Brain/embryology ; Evolution, Molecular ; Genome, Human ; Hominidae/embryology ; Hominidae/genetics ; Humans ; Mice ; Phylogeny
    Language Finnish
    Publishing date 2004
    Publishing country Finland
    Document type Comparative Study ; Editorial
    ZDB-ID 127604-9
    ISSN 0012-7183
    ISSN 0012-7183
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  6. Article ; Online: Simple 3D culture of dissociated kidney mesenchyme mimics nephron progenitor niche and facilitates nephrogenesis Wnt-independently.

    Dapkunas, Arvydas / Rantanen, Ville / Gui, Yujuan / Lalowski, Maciej / Sainio, Kirsi / Kuure, Satu / Sariola, Hannu

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 13433

    Abstract: Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a combination of ... ...

    Abstract Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a combination of 3D Matrigel and growth media supplemented with Fibroblast Growth Factor 2 (FGF2) and Src inhibitor PP2. This allows dissociated KM to spontaneously self-organize into spheres. To reassess the requirement of WNT activity in KM self-organization and NPs maintenance, cells were cultured with short pulse of high-dose GSK3β inhibitor BIO, on a constant low-dose or without BIO. Robust proliferation at 48 hours and differentiation at 1 week were observed in cultures with high BIO pulse. Importantly, dissociated KM cultured without BIO, similarly to that exposed to constant low dose of BIO, maintained NPs up to one week and spontaneously differentiated into nephron tubules at 3 weeks of culture. Our results show that KM is maintained and induced to differentiate in a simple culture system. They also imply that GSK3β/WNT-independent pathways contribute to the maintenance and induction of mouse KM. The robust and easy 3D culture enables further characterization of NPs, and may facilitate disease modeling when applied to human cells.
    MeSH term(s) Animals ; Cells, Cultured ; Culture Media/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta/metabolism ; Homeodomain Proteins/metabolism ; Indoles/pharmacology ; Kidney/cytology ; Kidney/embryology ; Mesoderm/cytology ; Mice ; Nephrons/cytology ; Nephrons/drug effects ; Organogenesis ; Oximes/pharmacology ; Stem Cell Niche ; Stem Cells/cytology ; Stem Cells/metabolism ; Tissue Culture Techniques/methods ; Transcription Factors/metabolism ; Wnt Signaling Pathway
    Chemical Substances 6-bromoindirubin-3'-oxime ; Culture Media ; Homeodomain Proteins ; Indoles ; Oximes ; Six2 protein, mouse ; Transcription Factors ; Fibroblast Growth Factor 2 (103107-01-3) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1)
    Language English
    Publishing date 2019-09-17
    Publishing country England
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-49526-x
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  7. Article: Elämän sattuma ja välttämättömyys.

    Sariola, Hannu

    Duodecim; laaketieteellinen aikakauskirja

    2002  Volume 118, Issue 23, Page(s) 2425–2431

    Title translation The chance and necessity of life.
    MeSH term(s) Amino Acids/chemical synthesis ; Animals ; Biological Evolution ; Earth (Planet) ; Hominidae ; Humans ; Life ; Origin of Life ; Philosophy
    Chemical Substances Amino Acids
    Language Finnish
    Publishing date 2002
    Publishing country Finland
    Document type Journal Article
    ZDB-ID 127604-9
    ISSN 0012-7183
    ISSN 0012-7183
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  8. Article: Nephron induction revisited: from caps to condensates.

    Sariola, Hannu

    Current opinion in nephrology and hypertension

    2002  Volume 11, Issue 1, Page(s) 17–21

    Abstract: Conversion of mesenchyme to epithelium in the metanephric kidney is clearly a multimolecular, multistep and partly redundant process. The present short review focuses on a neglected morphological aspect of kidney differentiation: the development of two ... ...

    Abstract Conversion of mesenchyme to epithelium in the metanephric kidney is clearly a multimolecular, multistep and partly redundant process. The present short review focuses on a neglected morphological aspect of kidney differentiation: the development of two transitory mesenchymal condensations that precede epithelial differentiation of nephrons. The first appearing condensate covers the tips of the collecting ducts and is termed a cap condensate. In the early kidney rudiment this structure has been referred to as a primary or early condensate. A few cells of the cap condensate (maybe only four to six cells), situated at the lateral edge of the cap, start proliferating rapidly and form a pretubular aggregate (or pretubular condensate), which converts to secretory nephron epithelia and finally segregates to different tubule segments. Throughout nephrogenesis, the cap condensates and pretubular aggregates are clearly distinguishable structures that show only partly overlapping gene expression profiles. Apart from being the source for the pretubular aggregates, the role of the cap condensate is unknown. It is now proposed that the cap regulates ureteric branching morphogenesis.
    MeSH term(s) Animals ; Embryonic and Fetal Development ; Epithelium/embryology ; Kidney Tubules/embryology ; Kidney Tubules, Collecting/embryology ; Mesoderm/physiology ; Nephrons/embryology
    Language English
    Publishing date 2002-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1151092-4
    ISSN 1535-3842 ; 1062-4821 ; 1062-4813
    ISSN (online) 1535-3842
    ISSN 1062-4821 ; 1062-4813
    DOI 10.1097/00041552-200201000-00003
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  9. Article: Nephron induction.

    Sariola, Hannu

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2002  Volume 17 Suppl 9, Page(s) 88–90

    Abstract: One of the most remarkable transformations of cells during organogenesis is the epithelial transformation of nephrogenic mesenchyme to secretory nephrons. During recent years, gene targeting and organ culture approaches have been used efficiently to ... ...

    Abstract One of the most remarkable transformations of cells during organogenesis is the epithelial transformation of nephrogenic mesenchyme to secretory nephrons. During recent years, gene targeting and organ culture approaches have been used efficiently to resolve key molecules involved in this multistage process. Nephrons are induced by the tips of the branching ureteric bud that later forms the collecting duct network. The first signal in nephron induction is obviously maintaining the mesenchyme; the second enhances cell proliferation and brings together the set of cells that contribute to one single nephron. This stage is characterized by two types of condensations (first the cap stage and then pre-tubular condensation). The final step, epithelial transformation, is a cell-autonomous process. Although the molecular cascade in nephron induction is being resolved in the rat, the same signals seem to work less efficiently in the mouse. In the rat, fibroblast growth factor-2 maintains the nephrogenic mesenchyme; leukaemia inhibitory factor together with transforming growth factor beta-2 induce its condensation; and autocrine secretion of Wnt-4 converts it to epithelium.
    MeSH term(s) Animals ; Embryonic and Fetal Development/physiology ; Fibroblast Growth Factor 2/physiology ; Growth Inhibitors/physiology ; Humans ; Interleukin-6 ; Leukemia Inhibitory Factor ; Lymphokines/physiology ; Nephrons/embryology ; Time Factors ; Transforming Growth Factor beta/physiology ; Transforming Growth Factor beta2
    Chemical Substances Growth Inhibitors ; Interleukin-6 ; LIF protein, human ; Leukemia Inhibitory Factor ; Lif protein, mouse ; Lymphokines ; TGFB2 protein, human ; Transforming Growth Factor beta ; Transforming Growth Factor beta2 ; Fibroblast Growth Factor 2 (103107-01-3)
    Language English
    Publishing date 2002
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/17.suppl_9.88
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  10. Article ; Online: Simple 3D culture of dissociated kidney mesenchyme mimics nephron progenitor niche and facilitates nephrogenesis Wnt-independently

    Arvydas Dapkunas / Ville Rantanen / Yujuan Gui / Maciej Lalowski / Kirsi Sainio / Satu Kuure / Hannu Sariola

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: Abstract Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a ... ...

    Abstract Abstract Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a combination of 3D Matrigel and growth media supplemented with Fibroblast Growth Factor 2 (FGF2) and Src inhibitor PP2. This allows dissociated KM to spontaneously self-organize into spheres. To reassess the requirement of WNT activity in KM self-organization and NPs maintenance, cells were cultured with short pulse of high-dose GSK3β inhibitor BIO, on a constant low-dose or without BIO. Robust proliferation at 48 hours and differentiation at 1 week were observed in cultures with high BIO pulse. Importantly, dissociated KM cultured without BIO, similarly to that exposed to constant low dose of BIO, maintained NPs up to one week and spontaneously differentiated into nephron tubules at 3 weeks of culture. Our results show that KM is maintained and induced to differentiate in a simple culture system. They also imply that GSK3β/WNT-independent pathways contribute to the maintenance and induction of mouse KM. The robust and easy 3D culture enables further characterization of NPs, and may facilitate disease modeling when applied to human cells.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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