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  1. Article ; Online: Therapeutic implications of the interplay between interferons and ER in breast cancer.

    Todorović-Raković, Nataša / Whitfield, Jonathan R

    Cytokine & growth factor reviews

    2024  Volume 75, Page(s) 119–125

    Abstract: The involvement of interferons (IFNs) in various diseases, including breast cancer, has sparked controversy due to their diverse roles in immunity and significant impact on pathological mechanisms. In the context of breast cancer, the heightened ... ...

    Abstract The involvement of interferons (IFNs) in various diseases, including breast cancer, has sparked controversy due to their diverse roles in immunity and significant impact on pathological mechanisms. In the context of breast cancer, the heightened expression of endogenous IFNs has been linked to anti-tumor activity and a favorable prognosis for patients. Within the tumor tissue and microenvironment, IFNs initiate a cascade of molecular events involving numerous factors, which can lead to either cooperative or repressive interactions. The specific functions of IFNs in breast cancer vary depending on the two major disease phenotypes: hormone dependent (or responsive) and hormone independent (or unresponsive) breast cancer. Hormone dependence is determined by the presence of estrogen receptors (ERs). The interplay between the IFN and ER signaling pathways, and the involvement of intermediate factors such as NFκB, are areas that have been somewhat under-researched, but that hold potential importance for the understanding and treatment of breast cancer. This review aims to provide a comprehensive overview of the actions of IFNs in breast cancer, particularly in relation to the different breast cancer phenotypes and the significance of comprehending the underlying mechanisms. Furthermore, the use of IFN-based therapies in cancer treatment remains a topic of debate and has not yet gained widespread acceptance. However, emerging discoveries may redirect focus towards the potential of IFN-based therapies.
    MeSH term(s) Humans ; Female ; Interferons/therapeutic use ; Interferons/metabolism ; Breast Neoplasms/drug therapy ; Signal Transduction ; Hormones/therapeutic use ; Tumor Microenvironment
    Chemical Substances Interferons (9008-11-1) ; Hormones
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330534-7
    ISSN 1879-0305 ; 1359-6101
    ISSN (online) 1879-0305
    ISSN 1359-6101
    DOI 10.1016/j.cytogfr.2024.01.002
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  2. Article ; Online: Chromogenic In Situ Hybridization (CISH) as a Method for Detection of C-Myc Amplification in Formalin-Fixed Paraffin-Embedded Tumor Tissue: An Update.

    Todorović-Raković, Nataša

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2318, Page(s) 313–320

    Abstract: In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations, or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in ... ...

    Abstract In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations, or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in interphase nuclei of target tissue. However, chromogenic in situ hybridization (CISH) is also applicable to formalin-fixed, paraffin-embedded (FFPE ) tissues, besides metaphase chromosome spreads. CISH is similar to fluorescent in situ hybridization (FISH) regarding pretreatments and hybridization protocols but differs in the way of visualization. Indeed, CISH signal detection is similar to that used in immunohistochemistry, making use of a peroxidase-based chromogenic reaction instead of fluorescent dyes. In particular, tagged DNA probes are indirectly detected using an enzyme-conjugated antibody targeting the tags. The enzymatic reaction of the chromogenic substrate leads to the formation of strong permanent brown signals that can be visualized by bright-field microscopy at 40× magnification. The advantage of CISH is that it allows the simultaneous observation of gene amplification and tissue morphology, and the slides can be stored for a long time.
    MeSH term(s) Chromogenic Compounds/chemistry ; DNA/genetics ; DNA Probes ; Gene Amplification ; Genes, myc/genetics ; Genes, myc/physiology ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization/methods ; In Situ Hybridization, Fluorescence/methods ; Neoplasms ; Paraffin Embedding/methods ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/immunology ; Proto-Oncogene Proteins c-myc/metabolism ; Translocation, Genetic
    Chemical Substances Chromogenic Compounds ; DNA Probes ; Proto-Oncogene Proteins c-myc ; DNA (9007-49-2)
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1476-1_17
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  3. Article ; Online: The role of cytokines in the evolution of cancer: IFN-γ paradigm.

    Todorović-Raković, Nataša

    Cytokine

    2021  Volume 151, Page(s) 155442

    Abstract: The evolution of malignant cells implies an increase in oncogenic fitness of cells which arises in active and reciprocal interaction with the tumor microenvironment. The mechanisms facilitating the adaptive evolution of cancer cells involve clonal ... ...

    Abstract The evolution of malignant cells implies an increase in oncogenic fitness of cells which arises in active and reciprocal interaction with the tumor microenvironment. The mechanisms facilitating the adaptive evolution of cancer cells involve clonal selection of cancer cells, in a direction of increased adaptive potential under the selective pressure of host defensive strategies. Once reached, this potential could go the other way, changing the same evolutionary force in the tumor microenvironment which influenced its emergence and favoring cancer progression. The immunological system as a part of host defensive mechanisms could be an effective modulator of cancer evolution/progression since it is also a major source of cellular intermediators, such as cytokines. The exemplar of IFN-γ actions during cancer evolution could help the revealing of these mutual interactions and enable better insight into the complex nature of cancer disease, leading to a new approach to treatment strategies.
    MeSH term(s) Cytokines ; Humans ; Interferon-gamma ; Neoplasms ; Tumor Microenvironment
    Chemical Substances Cytokines ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2021-01-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2021.155442
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  4. Article ; Online: The prognostic significance of serum interferon-gamma (IFN-γ) in hormonally dependent breast cancer.

    Todorović-Raković, Nataša / Milovanović, Jelena / Greenman, John / Radulovic, Marko

    Cytokine

    2022  Volume 152, Page(s) 155836

    Abstract: Background: Interferon-γ (IFN-γ) is a pleiotropic immunomodulatory cytokine. Because of its contradictory and even dualistic roles in malignancies, its potential as a biomarker remains to be unraveled.: Aim: To evaluate the prognostic significance of ...

    Abstract Background: Interferon-γ (IFN-γ) is a pleiotropic immunomodulatory cytokine. Because of its contradictory and even dualistic roles in malignancies, its potential as a biomarker remains to be unraveled.
    Aim: To evaluate the prognostic significance of serum IFN-γ in hormonally treated breast cancer patients.
    Material and methods: The study included 72 premenopausal breast cancer patients with known clinicopathological characteristics. All patients received adjuvant hormonal therapy based on hormone receptor-positivity. The median follow-up period was 93 months. IFN-γ serum protein levels were determined by quantitative ELISA. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analyses. Classification of patients into IFN-γ
    Results: The best prognostic performance was achieved by IFN-γ (AUC = 0.24 and p = 0.01 for distant events, AUC = 0.29 and p = 0.01 for local and distant events combined). Age and IFN-γ were prognostically significant in instances of all types of outcomes and IFN-γ was the independent prognostic parameter (Cox regression). There was a significant difference between IFN-γ values of patients without any events and those with distant metastases (Mann-Whitney test, p = 0.007). IFN-γ levels correlated significantly with nodal status and tumor stage (Spearman's rank order, r = -0.283 and r = -0.238, respectively). Distant recurrence incidence was 4% for the IFN-γ
    Conclusions: Raised serum IFN-γ levels associate independently with favorable disease outcome in hormonally dependent breast cancer.
    MeSH term(s) Biomarkers, Tumor ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Female ; Humans ; Interferon-gamma ; Kaplan-Meier Estimate ; Prognosis
    Chemical Substances Biomarkers, Tumor ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2022-02-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2022.155836
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  5. Article ; Online: Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease.

    Todorović-Raković, Nataša / Whitfield, Jonathan R

    Cytokine

    2021  Volume 146, Page(s) 155637

    Abstract: Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a ... ...

    Abstract Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections. Here we consider the controversial roles of effectors like IFNγ, discussing its actions in immunomodulation and immunotolerance. We explore the possibility that modulation of IFNγ could be used to influence the course of such infections. Importantly, not only could endogenous expression of IFNγ influence the outcome, there are existing IFNγ therapeutics that can readily be applied in the clinic. However, our understanding of the molecular mechanisms controlled by IFNγ suggests that the exact timing for application of IFNγ-based therapeutics could be crucial: it should be earlier to significantly reduce the viral load and thus decrease the overall severity of the disease.
    MeSH term(s) Adaptive Immunity/immunology ; Antiviral Agents/immunology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/immunology ; COVID-19/virology ; Humans ; Immune Tolerance/immunology ; Immunity, Innate/immunology ; Interferon-gamma/immunology ; Interferon-gamma/therapeutic use ; Receptors, Interferon/immunology ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Signal Transduction/immunology
    Chemical Substances Antiviral Agents ; Receptors, Interferon ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2021-07-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2021.155637
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  6. Article ; Online: Vascular endothelial growth factor (VEGF) -A, -C and VE-cadherin as potential biomarkers in early breast cancer patients.

    Milovanović, Jelena / Vujasinović, Tijana / Todorović-Raković, Nataša / Greenman, John / Hranisavljević, Jelena / Radulovic, Marko

    Pathology, research and practice

    2023  Volume 252, Page(s) 154923

    Abstract: Background: Vascular endothelial growth factor (VEGF) -A and -C act as multifunctional molecules and growth factors, while VE-cadherin (cadherin 5, CDH5) is the endothelial junction protein.: Aim: To assess the relationship between intratumoral VEGF - ...

    Abstract Background: Vascular endothelial growth factor (VEGF) -A and -C act as multifunctional molecules and growth factors, while VE-cadherin (cadherin 5, CDH5) is the endothelial junction protein.
    Aim: To assess the relationship between intratumoral VEGF -A, -C and CDH5 levels and clinical outcome, in primary, early-stage, breast cancer patients.
    Patients and methods: The study included 69 node-negative (N0) breast cancer patients, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would affect the course of disease. The median follow-up period was 144 months. Intratumoral mRNA levels of VEGF -A, -C and CDH5 were determined by RT-qPCR. Prognostic performance was evaluated by Cox proportional hazards regression, Kaplan-Meier analysis, as well as by the multivariable approach based on the least absolute shrinkage and selection operator (LASSO) logit regression. Classification of patients into the low and high subgroups was performed using the outcome-oriented cut-off point categorization approach.
    Results: Of the measured mRNAs, only CDH5 mRNA (t = -2.17; p = 0.04) and VEGF-C mRNA (t = -2.41; p = 0.03) showed significant differences between values in patient subgroups with distant metastasis and those without recurrences, respectively. These t-test results were in agreement with the Cox regression by which CDH5 mRNA reached the most pronounced hazard ratio (HR=2.07; p = 0.05), followed by VEGF-C mRNA (HR=1.59; p = 0.005). HR values above 1.0 indicate that high levels of either CDH5 or VEGF-C mRNAs associated with a higher risk of poor clinical outcome. Distant recurrence incidence was 26% for the CDH5
    Conclusion: Intratumoral VEGF-A levels did not associate with disease outcome in primary, early-stage, breast cancer patients, whilst raised levels of either CDH5 or VEGF-C prognosticated a high risk of distant metastasis.
    MeSH term(s) Humans ; Female ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Vascular Endothelial Growth Factor C/genetics ; Vascular Endothelial Growth Factor C/metabolism ; Antigens, CD/metabolism ; Vascular Endothelial Growth Factors ; Prognosis ; RNA, Messenger/genetics ; Biomarkers, Tumor/analysis
    Chemical Substances Vascular Endothelial Growth Factor A ; cadherin 5 ; Vascular Endothelial Growth Factor C ; Antigens, CD ; Vascular Endothelial Growth Factors ; RNA, Messenger ; Biomarkers, Tumor
    Language English
    Publishing date 2023-11-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2023.154923
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  7. Article ; Online: The significance of HOXB7 and IL17RB serum levels in prognosis of hormonally dependent breast cancer: A pilot study.

    Todorović-Raković, Nataša / Milovanović, Jelena / Greenman, John / Radulovic, Marko

    Advances in medical sciences

    2021  Volume 66, Issue 2, Page(s) 359–365

    Abstract: Purpose: Improved prognostication of a patient's outcome could allow for personalized treatment decisions in breast cancer. Homeobox B7 (HOXB7) and interleukin 17 receptor B (IL17RB) are proteins reportedly involved in the development of hormonal ... ...

    Abstract Purpose: Improved prognostication of a patient's outcome could allow for personalized treatment decisions in breast cancer. Homeobox B7 (HOXB7) and interleukin 17 receptor B (IL17RB) are proteins reportedly involved in the development of hormonal therapy resistance. Their prognostic value was previously investigated in tumor tissue but recent mass spectrometric detection of HOXB7 and IL17RB proteins in serum has prompted us to perform the first prognostic evaluation of their serum levels.
    Patients and methods: The study included 81 premenopausal breast cancer patients that received adjuvant hormonal therapy. The median follow-up period was 61 months. HOXB7 and IL17RB serum protein levels were measured by quantitative sandwich ELISA and prognostically evaluated by Cox proportional hazards regression analysis.
    Results: HOXB7 protein was detected in 96.3% and IL17RB in 33.3% of serum samples. Higher levels of serum HOXB7 significantly associated with favorable disease outcome by prognosticating distant (by HR ​= ​0.04; P ​= ​0.001) and local recurrence (by HR ​= ​0.03, P ​= ​0.001). The recurrence rates in the HOXB7
    Conclusions: Our findings validate the previous mass-spectrometry data by showing that HOXB7 and IL17RB cellular proteins are detectable in serum by a standard ELISA assay. Furthermore, we show that HOXB7 serum levels are the relevant prognosticator of response to hormonal therapy.
    MeSH term(s) Biomarkers, Tumor ; Breast Neoplasms/drug therapy ; Female ; Homeodomain Proteins ; Humans ; Pilot Projects ; Prognosis ; Receptors, Estrogen ; Receptors, Interleukin-17
    Chemical Substances Biomarkers, Tumor ; HOXB7 protein, human ; Homeodomain Proteins ; IL17RB protein, human ; Receptors, Estrogen ; Receptors, Interleukin-17
    Language English
    Publishing date 2021-07-22
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2273668-2
    ISSN 1898-4002 ; 1896-1126
    ISSN (online) 1898-4002
    ISSN 1896-1126
    DOI 10.1016/j.advms.2021.07.007
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  8. Article ; Online: The prognostic value of cyclin D1 in breast cancer patients treated with hormonal therapy: A pilot study.

    Todorović-Raković, Nataša / Milovanović, Jelena / Durosaro, Samuel Olutunde / Radulovic, Marko

    Pathology, research and practice

    2021  Volume 222, Page(s) 153430

    Abstract: The aim: of the study was to determine the clinical relevance of cyclin D1 (cD1) and its association with clinicopathological parameters in breast cancer patients treated with hormonal therapy.: Material and methods: The study included 96 primary ... ...

    Abstract The aim: of the study was to determine the clinical relevance of cyclin D1 (cD1) and its association with clinicopathological parameters in breast cancer patients treated with hormonal therapy.
    Material and methods: The study included 96 primary breast cancer patients with known clinicopathological parameters. In adjuvant setting, 44 patients were tamoxifen-treated and 52 were treated with ovarian irradiation/ablation. The cD1 status (gene amplified/nonamplified) was determined on formalin-fixed paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. Associations between parameters were analyzed by Chi-square and Spearman's rank order correlation tests. Cox proportional hazards regression test was performed. Survival curves for relapse-free survival were constructed according to the Kaplan-Meier method.
    Results: There were no significant associations between cyclin D1 and clinicopathological parameters in either patient group. Amplified cyclin D1 associated significantly with the actual relapse incidence in the ovarian ablation patient group (p = 0.01, HR = 3.1), but not in the tamoxifen-treated patient group. Estrogen receptor and cyclin D1 have proven to be independent parameters of poor outcome in the ovarian ablation patient group (p = 0.03, HR = 2.9; and p = 0.009, HR = 2.5; respectively).
    Conclusions: Cyclin D1 might be a candidate biomarker of poor outcome in breast cancer patients treated with ovarian ablation, suggesting its possible involvement in acquirement of hormonal resistance. The role of cyclin D1 as potential parameter of response to tamoxifen was not as pronounced.
    MeSH term(s) Adult ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cyclin D1/drug effects ; Cyclin D1/metabolism ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy ; Prognosis ; Receptors, Estrogen/drug effects ; Tamoxifen/pharmacology ; Tamoxifen/therapeutic use
    Chemical Substances CCND1 protein, human ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45) ; Cyclin D1 (136601-57-5)
    Language English
    Publishing date 2021-04-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2021.153430
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  9. Article ; Online: Can granulysin provide prognostic value in primary breast cancer?

    Milovanović, Jelena / Todorović-Raković, Nataša / Vujasinović, Tijana / Greenman, John / Mandušić, Vesna / Radulovic, Marko

    Pathology, research and practice

    2022  Volume 237, Page(s) 154039

    Abstract: Background: Granulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer.: Aim: To ...

    Abstract Background: Granulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer.
    Aim: To evaluate the prognostic value of intratumoral GNLY in primary breast cancer patients and its association with established clinicopathological parameters.
    Patients and methods: The study included 69 node-negative breast cancer patients with known clinicopathological parameters, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would interfere with the course of disease. The median follow-up period was 144 months. Steroid hormone receptor status was determined by ligand-binding assay and HER2 status by chromogenic in situ hybridisation (CISH). Intratumoral GNLY mRNA levels were determined by RT-qPCR. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analysis. Classification of patients into GNLY
    Results: There was a significant difference between GNLY values of patients without any recurrences and those with local or distant recurrences (Mann-Whitney test, p = 0.05 and p = 0.02, respectively). None of the tested parameters showed prognostic significance for local and distant recurrences when combined. When distant metastases and local recurrences were separated as events, the best prognostic performance was observed for GNLY as compared with any clinicopathological parameter (AUC=0.24 and p = 0.04 for local events; AUC=0.71 and p = 0.03 for distant events). Local recurrence incidence was 0% for the GNLY
    Conclusion: High levels of granulysin prognosticate low risk of local recurrence but a high risk of distant metastasis in primary, untreated, breast cancer patients.
    MeSH term(s) Humans ; Female ; Prognosis ; Breast Neoplasms/pathology ; Alarmins/therapeutic use ; Ligands ; Neoplasm Recurrence, Local/pathology ; RNA, Messenger ; Steroids/therapeutic use ; Hormones/therapeutic use
    Chemical Substances Alarmins ; Ligands ; RNA, Messenger ; Steroids ; Hormones
    Language English
    Publishing date 2022-07-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2022.154039
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  10. Article ; Online: Detection of c-myc amplification in formalin-fixed paraffin-embedded tumor tissue by chromogenic in situ hybridization (CISH).

    Todorović-Raković, Nataša

    Methods in molecular biology (Clifton, N.J.)

    2013  Volume 1012, Page(s) 249–254

    Abstract: In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in ... ...

    Abstract In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in interphase nuclei of target tissue. However, chromogenic in situ hybridization (CISH) is also applicable to formalin-fixed, paraffin-embedded (FFPE) tissues, besides metaphase chromosome spreads. CISH is similar to fluorescent in situ hybridization (FISH) regarding pretreatments and hybridization protocols but differs in the way of visualization. Indeed, CISH signal detection is similar to that used in immunohistochemistry, making use of a peroxidase-based chromogenic reaction instead of fluorescent dyes. In particular, tagged DNA probes are indirectly detected using an enzyme-conjugated antibody targeting the tags. The enzymatic reaction of the chromogenic substrate leads to the formation of strong permanent brown signals that can be visualized by bright-field microscopy at 40 × magnification. The advantage of CISH is that it allows the simultaneous observation of gene amplification and tissue morphology and the slides can be stored for a long time.
    MeSH term(s) Gene Amplification ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization/methods ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism
    Chemical Substances Proto-Oncogene Proteins c-myc
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-429-6_17
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