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  • Proceedings of the National Academy of Sciences  (3)
  • 1
    Online Resource
    Online Resource
    p53 gene mutations are not required for early dissemination of cancer cells
    Proceedings of the National Academy of Sciences ; 1999
    In:  Proceedings of the National Academy of Sciences Vol. 96, No. 12 ( 1999-06-08), p. 6942-6946
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 12 ( 1999-06-08), p. 6942-6946
    Abstract: The p53 protein is involved in several central cellular processes, including gene transcription, DNA repair, cell cycling, genomic stability, chromosomal segregation, senescence, and apoptosis. p53 mutations frequently result in an immunocytochemically detectable accumulation of the p53 protein in tumor cells. To evaluate whether p53 gene mutations are required for the onset of hematogeneous tumor cell dissemination, we compared the p53 status of primary and micrometastatic tumor cells. Disseminated carcinoma cells could be detected in bone marrow aspirates obtained from 46 (40%) of 114 patients with various types of epithelial tumors without overt skeleton metastases. There was no correlation between the detection of p53 protein in primary lung carcinomas and the presence of tumor cells in bone marrow. Further analyses revealed that the disseminated carcinoma cells rarely accumulate mutated p53 protein and that 10 cell lines derived thereof did not harbor p53 mutations even in the presence of such mutations in the autologous primary tumors. These observations indicate that tumor cells can leave the primary tumor before mutations of the p53 gene occur and that these mutations are not essential for such early hematogeneous dissemination of cancer cells. Thus, the value of mutated p53 as a target for diagnosis and treatment of micrometastatic disease in cancer patients is questionable.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.96.12.6942
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1999
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 4 ( 2002-02-19), p. 2246-2251
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 4 ( 2002-02-19), p. 2246-2251
    Abstract: Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate ( n = 46), breast ( n = 45), colon ( n = 33), and kidney ( n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt metastases [tumor-node-metastasis (TNM)-stage UICC (Union Internationale Contre le Cancer) I-III]. After bone marrow was cultured for 21–102 days under special cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 124 patients (81%). The cultured epithelial cells harbored Ki-ras2 mutations and numerical chromosomal aberrations. The highest median number of expanded tumor cells was observed in prostate cancer (2,619 per flask). There was a significant positive correlation between the number of expanded tumor cells and the UICC-stage of the patients ( P = 0.03) or the presence of overt metastases ( P = 0.04). Moreover, a strong expansion of tumor cells was correlated to an increased rate of cancer-related deaths ( P = 0.007) and a reduced survival of the patients ( P = 0.006). In conclusion, the majority of cancer patients have viable tumor cells in their bone marrow at primary tumor diagnosis, and the proliferative potential of these cells determines the clinical outcome.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.042372199
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    From latent disseminated cells to overt metastasis: Genetic analysis of systemic breast cancer progression
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 13 ( 2003-06-24), p. 7737-7742
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 13 ( 2003-06-24), p. 7737-7742
    Abstract: According to the present view, metastasis marks the end in a sequence of genomic changes underlying the progression of an epithelial cell to a lethal cancer. Here, we aimed to find out at what stage of tumor development transformed cells leave the primary tumor and whether a defined genotype corresponds to metastatic disease. To this end, we isolated single disseminated cancer cells from bone marrow of breast cancer patients and performed single-cell comparative genomic hybridization. We analyzed disseminated tumor cells from patients after curative resection of the primary tumor (stage M0), as presumptive progenitors of manifest metastasis, and from patients with manifest metastasis (stage M1). Their genomic data were compared with those from microdissected areas of matched primary tumors. Disseminated cells from M0-stage patients displayed significantly fewer chromosomal aberrations than primary tumors or cells from M1-stage patients ( P 〈 0.008 and P 〈 0.0001, respectively), and their aberrations appeared to be randomly generated. In contrast, primary tumors and M1 cells harbored different and characteristic chromosomal imbalances. Moreover, applying machine-learning methods for the classification of the genotypes, we could correctly identify the presence or absence of metastatic disease in a patient on the basis of a single-cell genome. We suggest that in breast cancer, tumor cells may disseminate in a far less progressed genomic state than previously thought, and that they acquire genomic aberrations typical of metastatic cells thereafter. Thus, our data challenge the widely held view that the precursors of metastasis are derived from the most advanced clone within the primary tumor.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1331931100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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