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  1. Article: BIRC3 and BIRC5: multi-faceted inhibitors in cancer.

    Frazzi, Raffaele

    Cell & bioscience

    2021  Volume 11, Issue 1, Page(s) 8

    Abstract: Background: The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight ...

    Abstract Background: The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight members of the human IAPs family. This family is characterized by the presence of the baculoviral IAP repeat (BIR) domains, involved in protein-protein interactions. In addition to the BIR domains, IAPs also contain other important domains like the C-terminal ubiquitin-conjugating (UBC) domain, the caspase recruitment (CARD) domain and the C-terminal Ring zinc-finger (RING) domain.
    Main body: BIRC3 and BIRC5 have been characterized in some solid and hematological tumors and are therapeutic targets for the family of drugs called "Smac mimetics". Many evidences point to the pro-survival and antiapoptotic role of BIRC3 in cancer cells, however, not all the data are consistent and the resulting picture is heterogeneous. For instance, BIRC3 genetic inactivation due to deletions or point mutations is consistently associated to shorter progression free survival and poor prognosis in chronic lymphocytic leukemia patients. BIRC3 inactivation has also been associated to chemoimmunotherapy resistance. On the contrary, the progression from low grade gliomas to high grade gliomas is accompanied by BIRC3 expression increase, which bears relevant prognostic consequences. Due to the relationship between BIRC3, MAP3K14 and the non-canonical NF-kB pathway, BIRC3 inactivation bears consequences also on the tumor cells relying on NF-kB pathway to survive. BIRC5, on the contrary, is commonly considered an anti-apoptotic molecule, promoting cell division and tumor progression and it is widely regarded as potential therapeutic target.
    Conclusions: The present manuscript collects and reviews the most recent literature concerning the role played by BIRC3 and BIRC5 in cancer cells, providing useful information for the choice of the best therapeutic targets.
    Language English
    Publishing date 2021-01-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-020-00521-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: SIRT1 in Secretory Organ Cancer.

    Frazzi, Raffaele

    Frontiers in endocrinology

    2018  Volume 9, Page(s) 569

    Abstract: Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [1, 2, 3, 4]. A recent meta-analysis conducted on 37 selected studies of human ... ...

    Abstract Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [1, 2, 3, 4]. A recent meta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression [5]. This study reported that SIRT1 overexpression was associated with a worse OS in liver and lung cancers, while it was not correlated with OS in breast cancer, colorectal cancer, or gastric carcinoma. Collectively, the meta-analysis revealed that an unfavorable OS was associated with SIRT1 expression for solid malignancies. Given the growing importance of this class of lysine/histone deacetylases in human endocrine malignancies, a rational and focused literature assessment is desirable in light of future clinical translations.
    Language English
    Publishing date 2018-09-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2018.00569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Significance of Microenvironmental and Circulating Lactate in Breast Cancer.

    Frisardi, Vincenza / Canovi, Simone / Vaccaro, Salvatore / Frazzi, Raffaele

    International journal of molecular sciences

    2023  Volume 24, Issue 20

    Abstract: Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and ...

    Abstract Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and under hypoxic conditions, this leads toward the acidification of the extracellular matrix. The ability to shift between different metabolic pathways is a characteristic of breast cancer cells and is associated with an aggressive phenotype. Furthermore, the preliminary scientific evidence concerning the levels of circulating lactate in breast cancer points toward a correlation between hyperlactacidemia and poor prognosis, even though no clear linkage has been demonstrated. Overall, lactate may represent a promising metabolic target that needs to be investigated in breast cancer.
    MeSH term(s) Humans ; Female ; Lactic Acid/metabolism ; Breast Neoplasms/metabolism ; Glucose/metabolism ; Glycolysis
    Chemical Substances Lactic Acid (33X04XA5AT) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-10-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms242015369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer.

    Cusenza, Vincenza Ylenia / Tameni, Annalisa / Neri, Antonino / Frazzi, Raffaele

    Frontiers in oncology

    2023  Volume 13, Page(s) 1063636

    Abstract: Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1- ... ...

    Abstract Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2'-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as "writers", "readers" and "erasers". m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.
    Language English
    Publishing date 2023-03-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1063636
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Methylation Heterogeneity and Gene Expression of SPG20 in Solid Tumors.

    Cusenza, Vincenza Ylenia / Braglia, Luca / Frazzi, Raffaele

    Genes

    2022  Volume 13, Issue 5

    Abstract: Introduction: The downregulation of the Spastic Paraplegia-20 (: Methods: We analyzed the data generated through Infinium Human Methylation 450 BeadChip arrays and RNA-seq approaches extrapolated from The Cancer Genome Atlas (TCGA) database. The ... ...

    Abstract Introduction: The downregulation of the Spastic Paraplegia-20 (
    Methods: We analyzed the data generated through Infinium Human Methylation 450 BeadChip arrays and RNA-seq approaches extrapolated from The Cancer Genome Atlas (TCGA) database. The statistics were performed with R 4.0.4.
    Results: We aimed to assess whether the hypermethylation of this target gene was a common characteristic among different tumors and if there was a correlation between the m-values and the gene expression in paired tumor versus solid tissue normal. Overall, our analysis highlighted that
    Conclusion: Our research, based on data mining from TCGA, evidences that colon and liver tumors display a consistent methylation heterogeneity compared to their normal counterparts. This parallels a downregulation of
    MeSH term(s) Carcinoma, Hepatocellular/genetics ; Cell Cycle Proteins/genetics ; DNA Methylation/genetics ; Gene Expression ; Humans ; Paraplegia/genetics
    Chemical Substances Cell Cycle Proteins
    Language English
    Publishing date 2022-05-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13050861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Spartin: At the crossroad between ubiquitination and metabolism in cancer.

    Cusenza, Vincenza Ylenia / Bonora, Elena / Amodio, Nicola / Frazzi, Raffaele

    Biochimica et biophysica acta. Reviews on cancer

    2022  Volume 1877, Issue 6, Page(s) 188813

    Abstract: SPART is a gene coding for a multifunctional protein called spartin, localized in various organelles of human cells. Mutations in the coding region are responsible for a hereditary form of spastic paraplegia called Troyer syndrome while the epigenetic ... ...

    Abstract SPART is a gene coding for a multifunctional protein called spartin, localized in various organelles of human cells. Mutations in the coding region are responsible for a hereditary form of spastic paraplegia called Troyer syndrome while the epigenetic silencing has been demonstrated for some types of tumors. The main functions of this gene are associated to endosomic trafficking and receptor degradation, microtubule interaction, cytokinesis, fatty acids and oxidative metabolism. Spartin has been shown to be a target regulated by STAT3 and localizes also at the level of the mitochondrial outer membrane, where it forms part of a complex maintaining the integrity of the membrane potential. The most recent evidences report a downregulation of spartin in tumor tissues when compared to adjacent normal samples. This intriguing evidence supports further research aimed at clarifying the role of this protein in cancer development and metabolism.
    MeSH term(s) Humans ; Cell Cycle Proteins/genetics ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/metabolism ; Ubiquitination ; Microtubules/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances Cell Cycle Proteins
    Language English
    Publishing date 2022-10-01
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2918802-7
    ISSN 1879-2561 ; 0304-419X
    ISSN (online) 1879-2561
    ISSN 0304-419X
    DOI 10.1016/j.bbcan.2022.188813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells.

    Frazzi, Raffaele / Guardi, Manuela

    Molecules (Basel, Switzerland)

    2017  Volume 22, Issue 6

    Abstract: Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further ...

    Abstract Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further the most recent and most promising among these molecular targets for a translational application.
    MeSH term(s) Anticarcinogenic Agents/therapeutic use ; Humans ; Leukemia/drug therapy ; Lymphoma/drug therapy ; Stilbenes/therapeutic use
    Chemical Substances Anticarcinogenic Agents ; Stilbenes ; resveratrol (Q369O8926L)
    Language English
    Publishing date 2017-05-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules22060885
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Copy Number Variation and Rearrangements Assessment in Cancer: Comparison of Droplet Digital PCR with the Current Approaches.

    Cusenza, Vincenza Ylenia / Bisagni, Alessandra / Rinaldini, Monia / Cattani, Chiara / Frazzi, Raffaele

    International journal of molecular sciences

    2021  Volume 22, Issue 9

    Abstract: The cytogenetic and molecular assessment of deletions, amplifications and rearrangements are key aspects in the diagnosis and therapy of cancer. Not only the initial evaluation and classification of the disease, but also the follow-up of the tumor rely ... ...

    Abstract The cytogenetic and molecular assessment of deletions, amplifications and rearrangements are key aspects in the diagnosis and therapy of cancer. Not only the initial evaluation and classification of the disease, but also the follow-up of the tumor rely on these laboratory approaches. The therapeutic choice can be guided by the results of the laboratory testing. Genetic deletions and/or amplifications directly affect the susceptibility or the resistance to specific therapies. In an era of personalized medicine, the correct and reliable molecular characterization of the disease, also during the therapeutic path, acquires a pivotal role. Molecular assays like multiplex ligation-dependent probe amplification and droplet digital PCR represent exceptional tools for a sensitive and reliable detection of genetic alterations and deserve a role in molecular oncology. In this manuscript we provide a technical comparison of these two approaches with the golden standard represented by fluorescence in situ hybridization. We also describe some relevant targets currently evaluated with these techniques in solid and hematologic tumors.
    MeSH term(s) Chromosome Aberrations ; DNA Copy Number Variations ; DNA, Neoplasm/genetics ; Digital Technology/methods ; Emulsions ; Endpoint Determination/methods ; Fluorometry ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence/methods ; Multiplex Polymerase Chain Reaction/methods ; Neoplasm Proteins/genetics ; Neoplasms/genetics ; Oncogene Proteins, Fusion/genetics ; Polymerase Chain Reaction/methods ; Sensitivity and Specificity
    Chemical Substances DNA, Neoplasm ; EML4-ALK fusion protein, human ; Emulsions ; Neoplasm Proteins ; Oncogene Proteins, Fusion
    Language English
    Publishing date 2021-04-29
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22094732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The multiple mechanisms of cell death triggered by resveratrol in lymphoma and leukemia.

    Frazzi, Raffaele / Tigano, Marco

    International journal of molecular sciences

    2014  Volume 15, Issue 3, Page(s) 4977–4993

    Abstract: Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death ... ...

    Abstract Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death triggered by- or linked to- resveratrol are reviewed and discussed. The main focus is on lymphoma and leukemia experimental models where resveratrol has been tested and investigated at the cellular, molecular or physiological levels. The most relevant in vivo challenges involving resveratrol are also reported and analyzed in order to define the key features of this polyphenol and the potential for the treatment of hematologic tumors.
    MeSH term(s) Angiogenesis Inhibitors/pharmacology ; Animals ; Apoptosis/drug effects ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Humans ; Leukemia/drug therapy ; Leukemia/metabolism ; Leukemia/pathology ; Lymphoma/drug therapy ; Lymphoma/metabolism ; Lymphoma/pathology ; Models, Biological ; Resveratrol ; Stilbenes/pharmacology
    Chemical Substances Angiogenesis Inhibitors ; Biomarkers, Tumor ; Stilbenes ; Resveratrol (Q369O8926L)
    Language English
    Publishing date 2014-03-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms15034977
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Use of FTA® classic cards for epigenetic analysis of sperm DNA.

    Serra, Olga / Frazzi, Raffaele / Perotti, Alessio / Barusi, Lorenzo / Buschini, Annamaria

    BioTechniques

    2018  Volume 64, Issue 2, Page(s) 45–51

    Abstract: FTA® technologies provide the most reliable method for DNA extraction. Although FTA technologies have been widely used for genetic analysis, there is no literature on their use for epigenetic analysis yet. We present for the first time, a simple method ... ...

    Abstract FTA® technologies provide the most reliable method for DNA extraction. Although FTA technologies have been widely used for genetic analysis, there is no literature on their use for epigenetic analysis yet. We present for the first time, a simple method for quantitative methylation assessment based on sperm cells stored on Whatman FTA classic cards. Specifically, elution of seminal DNA from FTA classic cards was successfully tested with an elution buffer and an incubation step in a thermocycler. The eluted DNA was bisulfite converted, amplified by PCR, and a region of interest was pyrosequenced.
    MeSH term(s) DNA/isolation & purification ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Male ; Specimen Handling ; Spermatozoa/chemistry
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2018-02-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 48453-2
    ISSN 1940-9818 ; 0736-6205
    ISSN (online) 1940-9818
    ISSN 0736-6205
    DOI 10.2144/btn-2017-0101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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