LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Back to previous search Search history
Advanced search

Your last searches

  1. AU="Kraggerud, Sigrid M"
  2. AU="Fakhry, Carole"

Search results

Result 1 - 10 of total 15

Search options

  1. Article ; Online: Evolutionary mode and timing of dissemination of high-grade serous carcinomas.

    Sveen, Anita / Johannessen, Bjarne / Klokkerud, Solveig Mk / Kraggerud, Sigrid M / Meza-Zepeda, Leonardo A / Bjørnslett, Merete / Bischof, Katharina / Myklebost, Ola / Taskén, Kjetil / Skotheim, Rolf I / Dørum, Anne / Davidson, Ben / Lothe, Ragnhild A

    JCI insight

    2024  Volume 9, Issue 3

    Abstract: Dissemination within the peritoneal cavity is a main determinant of poor patient outcomes from high-grade serous carcinomas (HGSCs). The dissemination process is poorly understood from a cancer evolutionary perspective. We reconstructed the evolutionary ... ...

    Abstract Dissemination within the peritoneal cavity is a main determinant of poor patient outcomes from high-grade serous carcinomas (HGSCs). The dissemination process is poorly understood from a cancer evolutionary perspective. We reconstructed the evolutionary trajectories across a median of 5 tumor sites and regions from each of 23 patients based on deep whole-exome sequencing. Polyclonal cancer origin was detected in 1 patient. Ovarian tumors had more complex subclonal architectures than other intraperitoneal tumors in each patient, which indicated that tumors developed earlier in the ovaries. Three common modes of dissemination were identified, including monoclonal or polyclonal dissemination of monophyletic (linear) or polyphyletic (branched) subclones. Mutation profiles of initial or disseminated clones varied greatly among cancers, but recurrent mutations were found in 7 cancer-critical genes, including TP53, BRCA1, BRCA2, and DNMT3A, and in the PI3K/AKT1 pathway. Disseminated clones developed late in the evolutionary trajectory models of most cancers, in particular in cancers with DNA damage repair deficiency. Polyclonal dissemination was predicted to occur predominantly as a single and rapid wave, but chemotherapy exposure was associated with higher genomic diversity of disseminated clones. In conclusion, we described three common evolutionary dissemination modes across HGSCs and proposed factors associated with dissemination diversity.
    MeSH term(s) Female ; Humans ; Mutation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Carcinoma
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.170423
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Frequent copy number gains of SLC2A3 and ETV1 in testicular embryonal carcinomas.

    Hoff, Andreas M / Kraggerud, Sigrid M / Alagaratnam, Sharmini / Berg, Kaja C G / Johannessen, Bjarne / Høland, Maren / Nilsen, Gro / Lingjærde, Ole C / Andrews, Peter W / Lothe, Ragnhild A / Skotheim, Rolf I

    Endocrine-related cancer

    2020  Volume 27, Issue 9, Page(s) 457–468

    Abstract: Testicular germ cell tumours (TGCTs) appear as different histological subtypes or mixtures of these. They show similar, multiple DNA copy number changes, where gain of 12p is pathognomonic. However, few high-resolution analyses have been performed and ... ...

    Abstract Testicular germ cell tumours (TGCTs) appear as different histological subtypes or mixtures of these. They show similar, multiple DNA copy number changes, where gain of 12p is pathognomonic. However, few high-resolution analyses have been performed and focal DNA copy number changes with corresponding candidate target genes remain poorly described for individual subtypes. We present the first high-resolution DNA copy number aberration (CNA) analysis on the subtype embryonal carcinomas (ECs), including 13 primary ECs and 5 EC cell lines. We identified recurrent gains and losses and allele-specific CNAs. Within these regions, we nominate 30 genes that may be of interest to the EC subtype. By in silico analysis of data from 150 TGCTs from The Cancer Genome Atlas (TCGA), we further investigated CNAs, RNA expression, somatic mutations and fusion transcripts of these genes. Among primary ECs, ploidy ranged between 2.3 and 5.0, and the most common aberrations were DNA copy number gains at chromosome (arm) 7, 8, 12p, and 17, losses at 4, 10, 11, and 18, replicating known TGCT genome characteristics. Gain of whole or parts of 12p was found in all samples, including a highly amplified 100 kbp segment at 12p13.31, containing SLC2A3. Gain at 7p21, encompassing ETV1, was the second most frequent aberration. In conclusion, we present novel CNAs and the genes located within these regions, where the copy number gain of SLC2A3 and ETV1 are of interest, and which copy number levels also correlate with expression in TGCTs.
    MeSH term(s) DNA Copy Number Variations/genetics ; DNA-Binding Proteins/genetics ; Glucose Transporter Type 3/genetics ; Humans ; Neoplasms, Germ Cell and Embryonal/genetics ; Testicular Neoplasms/genetics ; Transcription Factors/genetics
    Chemical Substances DNA-Binding Proteins ; ETV1 protein, human ; Glucose Transporter Type 3 ; SLC2A3 protein, human ; Transcription Factors
    Language English
    Publishing date 2020-08-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1218450-0
    ISSN 1479-6821 ; 1351-0088
    ISSN (online) 1479-6821
    ISSN 1351-0088
    DOI 10.1530/ERC-20-0064
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4192: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease.

    Landskron, Johannes / Kraggerud, Sigrid M / Wik, Elisabeth / Dørum, Anne / Bjørnslett, Merete / Melum, Espen / Helland, Øystein / Bjørge, Line / Lothe, Ragnhild A / Salvesen, Helga B / Taskén, Kjetil

    PloS one

    2017  Volume 12, Issue 7, Page(s) e0182030

    Abstract: The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in ... ...

    Abstract The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.
    MeSH term(s) Adult ; Aged ; Case-Control Studies ; Female ; Gene Frequency ; Humans ; Leukocyte Common Antigens/genetics ; Middle Aged ; Mutation, Missense ; Norway ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Polymorphism, Single Nucleotide
    Chemical Substances Leukocyte Common Antigens (EC 3.1.3.48) ; PTPRC protein, human (EC 3.1.3.48)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0182030
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    Brabrand, Sigmund / Johannessen, Bjarne / Axcrona, Ulrika / Kraggerud, Sigrid M / Berg, Kaja G / Bakken, Anne C / Bruun, Jarle / Fosså, Sophie D / Lothe, Ragnhild A / Lehne, Gustav / Skotheim, Rolf I

    Neoplasia (New York, N.Y.)

    2015  Volume 17, Issue 2, Page(s) 167–174

    Abstract: Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from ... ...

    Abstract Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.
    MeSH term(s) Adult ; Cell Lineage ; DNA Mutational Analysis ; Exome/genetics ; Germ-Line Mutation ; Humans ; Male ; Neoplasm Proteins/genetics ; Neoplasms, Germ Cell and Embryonal/genetics ; Neoplasms, Germ Cell and Embryonal/pathology ; Polymerase Chain Reaction/methods ; Proto-Oncogene Proteins c-kit/genetics ; Receptors, Platelet-Derived Growth Factor/genetics ; Sequence Analysis, DNA ; Testicular Neoplasms/genetics ; Testicular Neoplasms/pathology
    Chemical Substances Neoplasm Proteins ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptors, Platelet-Derived Growth Factor (EC 2.7.10.1)
    Language English
    Publishing date 2015-03-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2014.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5203: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study.

    Oldenburg, Jan / Kraggerud, Sigrid M / Brydøy, Marianne / Cvancarova, Milada / Lothe, Ragnhild A / Fossa, Sophie D

    Journal of translational medicine

    2007  Volume 5, Page(s) 70

    Abstract: Background: To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs).: Methods: A total of 238 TCSs, who had received ... ...

    Abstract Background: To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs).
    Methods: A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve years earlier, had participated in a long-term follow-up survey which assessed the prevalence of self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A-->G polymorphism at bp 304 in GSTP1, and deletions in GST-M1 and GST-T1. Evaluation of associations between GST polymorphisms and self-reported toxicities included adjustment for prior treatment.
    Results: All six evaluated toxicities were significantly associated with the cumulative dose of cisplatin and/or bleomycin. Compared to TCSs with either GSTP1-AG or GSTP1-AA, the 37 TCSs with the genotype GSTP1-GG, were significantly less bothered by paresthesias in fingers and toes (p = 0.039, OR 0.46 [0.22-0.96] and p = 0.023, OR 0.42 [0.20-0.88], respectively), and tinnitus (p = 0.008, OR 0.33 [0.14-0.74]). Furthermore, absence of functional GSTM1 protected against hearing impairment (p = 0.025, OR 1.81 [1.08-3.03]).
    Conclusion: In TCSs long-term self-reported chemotherapy-induced toxicities are associated with functional polymorphisms in GSTP1 and GSTM1. Hypothetically, absence of GST-M1 leaves more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of pro-apoptotic mediators represents a possible explanation of our findings. Genotyping of these GSTs might be a welcomed step towards a more individualized treatment of patients with metastatic testicular cancer.
    MeSH term(s) Adolescent ; Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/toxicity ; Cisplatin/therapeutic use ; Cisplatin/toxicity ; Cross-Sectional Studies ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Retrospective Studies ; Survivors ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/enzymology ; Testicular Neoplasms/genetics
    Chemical Substances Antineoplastic Agents ; Glutathione S-Transferase pi (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2007-12-27
    Publishing country England
    Document type Journal Article
    ISSN 1479-5876
    ISSN (online) 1479-5876
    DOI 10.1186/1479-5876-5-70
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors.

    Oldenburg, Jan / Kraggerud, Sigrid M / Cvancarova, Milada / Lothe, Ragnhild A / Fossa, Sophie D

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2007  Volume 25, Issue 6, Page(s) 708–714

    Abstract: Purpose: Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin- ... ...

    Abstract Purpose: Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs).
    Patients and methods: We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis.
    Results: The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR).
    Conclusion: The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
    MeSH term(s) Adolescent ; Adult ; Aged ; Audiometry ; Case-Control Studies ; Cisplatin/adverse effects ; Cisplatin/therapeutic use ; Confidence Intervals ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Hearing Loss/chemically induced ; Hearing Loss/diagnosis ; Hearing Loss/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Odds Ratio ; Probability ; Retrospective Studies ; Severity of Illness Index ; Survivors ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/genetics ; Testicular Neoplasms/mortality ; Testicular Neoplasms/pathology ; Time Factors
    Chemical Substances glutathione S-transferase T1 (EC 2.5.1.-) ; Glutathione S-Transferase pi (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2007-02-20
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2006.08.9599
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1847: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 650: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers

    Kærn Janne / Abeler Vera M / Kraggerud Sigrid M / Hoei-Hansen Christina E / Rajpert-De Meyts Ewa / Lothe Ragnhild A

    Molecular Cancer, Vol 6, Iss 1, p

    2007  Volume 12

    Abstract: Abstract Background Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various ... ...

    Abstract Abstract Background Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia. Results We examined in situ expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2γ) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13–40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence in situ hybridisation (FISH), and mutational analysis of the KIT oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, KIT was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH. Conclusion This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous KIT mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females.
    Keywords Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 616
    Language English
    Publishing date 2007-02-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study

    Brydøy Marianne / Kraggerud Sigrid M / Oldenburg Jan / Cvancarova Milada / Lothe Ragnhild A / Fossa Sophie D

    Journal of Translational Medicine, Vol 5, Iss 1, p

    2007  Volume 70

    Abstract: Abstract Background To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs). Methods A total of 238 TCSs, who had received ...

    Abstract Abstract Background To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs). Methods A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve years earlier, had participated in a long-term follow-up survey which assessed the prevalence of self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A→G polymorphism at bp 304 in GSTP1 , and deletions in GST-M1 and GST-T1 . Evaluation of associations between GST polymorphisms and self-reported toxicities included adjustment for prior treatment. Results All six evaluated toxicities were significantly associated with the cumulative dose of cisplatin and/or bleomycin. Compared to TCSs with either GSTP1-AG or GSTP1 - AA , the 37 TCSs with the genotype GSTP1-GG , were significantly less bothered by paresthesias in fingers and toes (p = 0.039, OR 0.46 [0.22–0.96] and p = 0.023, OR 0.42 [0.20–0.88], respectively), and tinnitus (p = 0.008, OR 0.33 [0.14–0.74]). Furthermore, absence of functional GSTM1 protected against hearing impairment (p = 0.025, OR 1.81 [1.08–3.03]). Conclusion In TCSs long-term self-reported chemotherapy-induced toxicities are associated with functional polymorphisms in GSTP1 and GSTM1 . Hypothetically, absence of GST-M1 leaves more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of pro-apoptotic mediators represents a possible explanation of our findings. Genotyping of these GSTs might be a welcomed step towards a more individualized treatment of patients with metastatic testicular cancer.
    Keywords Medicine ; R
    Subject code 150 ; 616
    Language English
    Publishing date 2007-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Article: Functional glutathione S-transferase genotypes among testicular germ cell tumor survivors: associations with primary and post-chemotherapy tumor histology.

    Kraggerud, Sigrid M / Oldenburg, Jan / Alnaes, Grethe I / Berg, Marianne / Kristensen, Vessela N / Fossa, Sophie D / Lothe, Ragnhild A

    Pharmacogenetics and genomics

    2009  Volume 19, Issue 10, Page(s) 751–759

    Abstract: Purpose: The pathogenesis of testicular germ cell tumor (TGCT) remains unknown. The aim of this study was to evaluate the pathogenic role of functional polymorphisms in detoxification enzymes among TGCT patients, through association studies of ... ...

    Abstract Purpose: The pathogenesis of testicular germ cell tumor (TGCT) remains unknown. The aim of this study was to evaluate the pathogenic role of functional polymorphisms in detoxification enzymes among TGCT patients, through association studies of constitutive genotypes and medical parameters before and after chemotherapy.
    Experimental design: Germline deletion polymorphisms in the glutathione S-transferase mu 1 (GSTM1) and the GST theta 1 (GSTT1), and a functional single nucleotide polymorphism in GST pi 1 (GSTP1, Ile105Val), were analyzed in TGCT survivors (TCSs) (n = 675) and controls (n = 189). Statistical analyses were performed for the genotype distributions between the TCSs and control populations, and between the genotypes and clinicopathological parameters of the TCSs.
    Results: The GST genotypes showed comparable distributions among the TCSs and the control population. However, the genotype combination GSTT1positive/GSTP1-GG or GSTP1-AG/GSTM1positive was more frequent among the TCSs [P = 0.050, odds ratio (OR): 1.47, 95% confidence interval (CI): 0.998-2.165]. The combined genotype GSTT1positive/GSTP1AA/GSTM1positive was associated with decreased risk of development of pure embryonal carcinoma (P = 0.009, OR: 0.309, 95% CI: 0.122-0.784) and the GSTP1-A-allele (i.e. genotypes GSTP-AA or GSTP-AG) was also associated with decreased risk for development of pure teratoma (P = 0.032, OR: 0.326, 95% CI: 0.122-0.873). Furthermore, the GSTP1-A-allele was overrepresented within the 'good prognosis group' (P = 0.032, OR: 2.407, 95% CI: 1.060-5.469), whereas the GSTM1nulltype was associated with the extent of TC qualifying as 'poor prognosis group' (P = 0.025, OR: 2.839, 95% CI: 1.104-7.301). The GSTP1-AG genotype was associated with necrosis in the tumor's post-chemotherapy histology (P = 0.001, OR: 16.087, 95% CI: 1.930-134.087). Failure, after platinum-based chemotherapy, was associated with the GSTT1positive/GSTP-AA or GSTP-GG/GSTM1-positive genotype (P = 0.019, OR: 2.168, 95% CI: 1.130-4.160).
    Conclusion: This study confirms an association between the GSTP1-G-allele and TGCT. Combinations of GST genotypes were associated with primary and post-chemotherapy tumor histology, and prognostic group presentation.
    MeSH term(s) Adolescent ; Adult ; Aged ; Genetic Predisposition to Disease ; Genotype ; Germinoma/genetics ; Germinoma/pathology ; Glutathione S-Transferase pi/genetics ; Glutathione S-Transferase pi/metabolism ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Polymorphism, Genetic ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/genetics ; Testicular Neoplasms/pathology
    Chemical Substances Glutathione S-Transferase pi (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione transferase T1-1, human (EC 2.5.1.18)
    Language English
    Publishing date 2009-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2175826-8
    ISSN 1744-6880 ; 1744-6872 ; 0960-314X
    ISSN (online) 1744-6880
    ISSN 1744-6872 ; 0960-314X
    DOI 10.1097/FPC.0b013e3283304253
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3660: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers.

    Hoei-Hansen, Christina E / Kraggerud, Sigrid M / Abeler, Vera M / Kaern, Janne / Rajpert-De Meyts, Ewa / Lothe, Ragnhild A

    Molecular cancer

    2007  Volume 6, Page(s) 12

    Abstract: Background: Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological ...

    Abstract Background: Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia.
    Results: We examined in situ expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2gamma) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13-40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence in situ hybridisation (FISH), and mutational analysis of the KIT oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, KIT was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH.
    Conclusion: This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous KIT mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females.
    MeSH term(s) Antigens, Neoplasm/analysis ; Biomarkers, Tumor/analysis ; Carcinoma, Embryonal/chemistry ; Carcinoma, Embryonal/genetics ; Carcinoma, Embryonal/pathology ; Carcinoma, Small Cell/chemistry ; Carcinoma, Small Cell/genetics ; Carcinoma, Small Cell/pathology ; Cell Cycle Proteins/analysis ; Cell Differentiation ; Cell Lineage ; Cell Transformation, Neoplastic/chemistry ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; DNA-Binding Proteins/analysis ; Dysgerminoma/chemistry ; Dysgerminoma/genetics ; Dysgerminoma/pathology ; Embryonal Carcinoma Stem Cells ; Female ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Neoplastic ; Gestational Age ; Gonadoblastoma/chemistry ; Gonadoblastoma/genetics ; Gonadoblastoma/pathology ; Homeodomain Proteins/analysis ; Humans ; Membrane Proteins/analysis ; Mutation ; Nanog Homeobox Protein ; Neoplasm Proteins/analysis ; Neoplastic Stem Cells/chemistry ; Neoplastic Stem Cells/pathology ; Octamer Transcription Factor-3/analysis ; Oogonia/chemistry ; Oogonia/pathology ; Ovarian Neoplasms/chemistry ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Ovary/chemistry ; Ovary/embryology ; Pluripotent Stem Cells/chemistry ; Pluripotent Stem Cells/pathology ; Proto-Oncogene Proteins c-kit/analysis ; Proto-Oncogene Proteins c-kit/genetics ; Transcription Factor AP-2/analysis
    Chemical Substances Antigens, Neoplasm ; Biomarkers, Tumor ; CTAG1B protein, human ; Cell Cycle Proteins ; DNA-Binding Proteins ; Homeodomain Proteins ; MAGEA4 protein, human ; Membrane Proteins ; NANOG protein, human ; Nanog Homeobox Protein ; Neoplasm Proteins ; Octamer Transcription Factor-3 ; POU5F1 protein, human ; TFAP2C protein, human ; TSPY1 protein, human ; Transcription Factor AP-2 ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
    Language English
    Publishing date 2007-02-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1476-4598
    ISSN (online) 1476-4598
    DOI 10.1186/1476-4598-6-12
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top