GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (3)
Material
Publisher
  • American Association for Cancer Research (AACR)  (3)
Person/Organisation
Language
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Abstract 367: Methods to enhance the optical resolution for 3D-SIM for the study of Hodgkin's lymphoma nuclei
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 367-367
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 367-367
    Abstract: In spite of a great deal of knowledge already available, the precise higher order organization of chromatin is still a subject of an debate. Moreover, cancerous cells have an altered chromatin organization in comparison to their healthy counterparts. This is also the case for Hodgkin's lymphoma (HL) - a lymphoid malignancy of B cell origin. HL comprises two cell types, the Hodgkin cells and the diagnostic bi- or multinucleated Reed-Sternberg (RS) cells readily distinguishable from healthy lymphocytes. Patient stratitifcation has been proposed through the quantitative analysis of 3D nuclear telomere organization. With the advent of super resolution microscopy (SRM), further insights into the spatial organization of the cancer genome become feasible. This includes the study of chromatin arrangement with SRM. However, its application to HL remains limited due to technical difficulties: HL cells display thickness of & gt;10µm resulting in light scattering and decreased signal-to-noise ratio. Structured Illumination Microscopy (SIM, a SRM type) in particular has advanced studies of the sub-cellular structures. It relies on projection of excitation pattern on to a fluorescently labeled sample. Sample's information is then shifted to a detectable band doubling the 3D resolution. Sample's refractive index homogeneity and counteracting photo-bleaching are both crucial for maintenance of the sharp illumination pattern and high-quality SIM, particularly in thick samples. Nevertheless, sample mounting media for SIM have not undergone a significant evolution since almost a decade. By identification and systematic comparison of non-hazardous components of mounting media we demonstrate increased sample's transparency and consequently improved SIM-quality. Using these novel sample clearing protocols we demonstrate high-resolution chromatin organization at ~120nm level in large RS cells of HL cell lines and in patient samples compared to lymphocytes. This work is of relevance of identification of new diagnostic structural biomarkers for HL. Citation Format: Aleksander T. Szczurek, Fabio Contu, Roberta Vanni, Hans Knecht, Nathalie Johnson, Tina Haliotis, Sabine Mai. Methods to enhance the optical resolution for 3D-SIM for the study of Hodgkin's lymphoma nuclei [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Ca ncer Res 2018;78(13 Suppl):Abstract nr 367.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-367
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 4725: The 3D nuclear telomere organization of Hodgkin-cells is different between patients entering rapid remission and patients with refractory or relapsing disease
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4725-4725
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4725-4725
    Abstract: Our recent study has utilized innovative 3D Q- FISH and three-dimensional (3D) imaging to define the 3D nuclear telomere organization in mono-nucleated Hodgkin (H) and multi-nucleated Reed-Sternberg (RS) cells of Hodgkin's lymphoma (HL) derived cell lines and diagnostic patient biopsies (Leukemia. 2009). These characteristics were found in both, classical EBV negative and EBV-associated, LMP1 expressing HL (Lab Invest. 2010). However, it is still unknown whether the 3D telomere profile at diagnostic biopsy is different in patients entering rapid remission after initiation of standard chemotherapy (ABVD) compared to patients with refractory or relapsing disease. In this study, we investigated by 3D telomere Q-FISH diagnostic biopsies of HL patients entering rapid complete remission and diagnostic biopsies from patients with refractory or relapsing disease. 8 diagnostic biopsies of 8 patients entering rapid remission (after 1-4 cycles of ABVD) and 8 diagnostic biopsies of 5 patients including 2 with primary refractory disease (progressing after 4-8 cycles of ABVD) and 3 cases relapsing 1-3 years after late remission (post 6 -8 cycles of ABVD) were analyzed the 3D telomeric structure by 3D Q-FISH and TeloView software (Cytometry A. 2005). We found that RS-cells of all patients from both groups showed significant increase in very short telomeres when compared to the mononuclear precursor H-cells (p & lt;0.01). Additionally, the number of telomere aggregates was significantly higher in RS cells than in H cells in both, the rapid remission group (p & lt;0.001) and the refractory or relapse group (p & lt;0.01). Most importantly, all diagnostic biopsies of the relapse group contained a very high percentage of very small telomeres in both, H-cells (72.4 ± 0.1%) and RS-cells (84.6 ± 9.9%). These differences were highly significant compared the percentage of very small telomeres of the rapid remission group for both, H-cells (40.0± 0.2%) (p=0.002) and RS-cells (59.9 ± 0.2%) (p=0.008). Remarkably, the percentage of very short telomeres was even higher in H-cells of the relapse group than in RS-cells of the rapid remission group. The average number of telomere aggregates per H-cell was significantly higher in the relapse group (3.8 ± 1.9) compared to that one in the rapid remission group (1.3 ± 0.6) (p=0.0003). RS-cells in the relapse contained still more telomere aggregates compared to RS cells of the remission group (5.8 ± 2.8 versus 3.1 ± 1.1) (p=0.03). However, H-cells of the relapse group contained already more aggregates than RS cells of the remission group (p: no significant). These results indicate that the 3D nuclear telomere organization of H and RS cells in refractory or relapsing patients is different from that of patients in rapid remission. In particular, the 3D nuclear telomere profile of H-cells allows identifying aggressive disease already at diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4725. doi:10.1158/1538-7445.AM2011-4725
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-4725
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract 3672: The three-dimensional (3D) spatial lamin A/C organization in normal lymphocytes, and in Hodgkin and Reed-Sternberg cells
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3672-3672
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3672-3672
    Abstract: Classical Hodgkin Lymphoma (HL) is a B-Cell lymphoma comprising mononucleated Hodgkin cells (H) and diagnostic bi- to multi-nucleated Reed Sternberg cells (RS). Genomic instability in HL is characterized by telomere dysfunction caused by critically short telomeres and telomere uncapping. Super resolution microscopy showed significant increases in the amount of DNA-poor nuclear spaces in HL compared to normal primary lymphocytes. A direct 3D interaction between telomeres and shelterin protein TRF2 is progressively disrupted from H to RS cells by either massive upregulation or downregulation of TRF2. TRF2 interacts with nuclear matrix protein lamin A/C in the maintenance of the 3D genome organization, which is disturbed in H and RS cells. Therefore we hypothesized that the TRF2- telomere-lamin A/C interaction is also disturbed in H and RS cells and leads to organizational alterations of the genome in HL. To this end, we analyzed lamin A/C expression levels of lymphocytes, H and RS cells and found that lamin A/C is upregulated in cancer cells compared to both activated and resting lymphocytes. The regular homogeneous and round shaped pattern found in lymphocytes was replaced in H and RS cells by a more irregular one, characterized by the presence of lamin A/C invaginations and septa that subdivide the nuclei into multiple smaller compartments. Our data show no co-localization between telomeres and lamin A/C in the DNA-poor spaces. Lamin A/C bordered the DNA-poor spaces but was never found inside them or in association with inner telomere fragments. 3D TRF-2 staining showed upregulation of the protein compared to normal lymphocytes, in correlation with the observation made in EBV-negative patients with clinically aggressive disease. The analysis of pre-treatment Hodgkin's patients' samples will allow to determine whether the TRF2-telomere-lamin A/C binding is different in patients with recurrent versus non-recurrent disease. Citation Format: Fabio Contu, Aleksander Szczurek, Roberta Vanni, Hans Knecht, Sabine Mai. The three-dimensional (3D) spatial lamin A/C organization in normal lymphocytes, and in Hodgkin and Reed-Sternberg cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3672.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-3672
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...