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  1. Article: The Role of Non-Coding RNAs in Autophagy During Carcinogenesis.

    de la Cruz-Ojeda, Patricia / Flores-Campos, Rocío / Navarro-Villarán, Elena / Muntané, Jordi

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 799392

    Abstract: Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as ... ...

    Abstract Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.
    Language English
    Publishing date 2022-03-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.799392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cancer Nano-Immunotherapy: The Novel and Promising Weapon to Fight Cancer.

    García-Domínguez, Daniel J / López-Enríquez, Soledad / Alba, Gonzalo / Garnacho, Carmen / Jiménez-Cortegana, Carlos / Flores-Campos, Rocío / de la Cruz-Merino, Luis / Hajji, Nabil / Sánchez-Margalet, Víctor / Hontecillas-Prieto, Lourdes

    International journal of molecular sciences

    2024  Volume 25, Issue 2

    Abstract: Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which ...

    Abstract Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano-immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.
    MeSH term(s) Humans ; Immunotherapy ; Neoplasms/therapy ; Antigen Presentation ; Immune Evasion ; Nanomedicine ; Tumor Microenvironment
    Language English
    Publishing date 2024-01-18
    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/ijms25021195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs.

    de la Cruz-Ojeda, Patricia / Flores-Campos, Rocío / Dios-Barbeito, Sandra / Navarro-Villarán, Elena / Muntané, Jordi

    International journal of molecular sciences

    2021  Volume 22, Issue 12

    Abstract: Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non- ... ...

    Abstract Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).
    MeSH term(s) Animals ; Cancer-Associated Fibroblasts/pathology ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Nitric Oxide/metabolism ; RNA, Long Noncoding/genetics ; Signal Transduction ; Tumor Microenvironment
    Chemical Substances RNA, Long Noncoding ; Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2021-06-10
    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/ijms22126264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials.

    Hontecillas-Prieto, Lourdes / Flores-Campos, Rocío / Silver, Andrew / de Álava, Enrique / Hajji, Nabil / García-Domínguez, Daniel J

    Frontiers in genetics

    2020  Volume 11, Page(s) 578011

    Abstract: Chemotherapy is one of the most established and effective treatments for almost all types of cancer. However, the elevated toxicity due to the non-tumor-associated effects, development of secondary malignancies, infertility, radiation-induced fibrosis ... ...

    Abstract Chemotherapy is one of the most established and effective treatments for almost all types of cancer. However, the elevated toxicity due to the non-tumor-associated effects, development of secondary malignancies, infertility, radiation-induced fibrosis and resistance to treatment limit the effectiveness and safety of treatment. In addition, these multiple factors significantly impact quality of life. Over the last decades, our increased understanding of cancer epigenetics has led to new therapeutic approaches and the promise of improved patient outcomes. Epigenetic alterations are commonly found in cancer, especially the increased expression and activity of histone deacetylases (HDACs). Dysregulation of HDACs are critical to the development and progression of the majority of tumors. Hence, HDACs inhibitors (HDACis) were developed and now represent a very promising treatment strategy. The use of HDACis as monotherapy has shown very positive pre-clinical results, but clinical trials have had only limited success. However, combinatorial regimens with other cancer drugs have shown synergistic effects both in pre-clinical and clinical studies. At the same time, these combinations have enhanced the efficacy, reduced the toxicity and tumor resistance to therapy. In this review, we will examine examples of HDACis used in combination with other cancer drugs and highlight the synergistic effects observed in recent preclinical and clinical studies.
    Language English
    Publishing date 2020-09-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2020.578011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

    Hontecillas-Prieto, Lourdes / García-Domínguez, Daniel J / Palazón-Carrión, Natalia / Martín García-Sancho, Alejandro / Nogales-Fernández, Esteban / Jiménez-Cortegana, Carlos / Sánchez-León, María L / Silva-Romeiro, Silvia / Flores-Campos, Rocío / Carnicero-González, Fernando / Ríos-Herranz, Eduardo / de la Cruz-Vicente, Fátima / Rodríguez-García, Guillermo / Fernández-Álvarez, Rubén / Martínez-Banaclocha, Natividad / Gumà-Padrò, Josep / Gómez-Codina, José / Salar-Silvestre, Antonio / Rodríguez-Abreu, Delvys /
    Gálvez-Carvajal, Laura / Labrador, Jorge / Guirado-Risueño, María / Provencio-Pulla, Mariano / Sánchez-Beato, Margarita / Marylene, Lejeune / Álvaro-Naranjo, Tomás / Casanova-Espinosa, María / Rueda-Domínguez, Antonio / Sánchez-Margalet, Víctor / de la Cruz-Merino, Luis

    Frontiers in immunology

    2024  Volume 15, Page(s) 1293931

    Abstract: Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients ... ...

    Abstract Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.
    Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.
    Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.
    Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.
    Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.
    MeSH term(s) Humans ; Biomarkers ; CD8-Positive T-Lymphocytes/pathology ; Killer Cells, Natural/pathology ; Lenalidomide/therapeutic use ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Non-Hodgkin ; Neoplasm Recurrence, Local/pathology ; Pathologic Complete Response
    Chemical Substances Biomarkers ; Lenalidomide (F0P408N6V4)
    Language English
    Publishing date 2024-02-26
    Publishing country Switzerland
    Document type Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1293931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.

    García-Domínguez, Daniel J / Hajji, Nabil / Sánchez-Molina, Sara / Figuerola-Bou, Elisabet / de Pablos, Rocío M / Espinosa-Oliva, Ana M / Andrés-León, Eduardo / Terrón-Camero, Laura Carmen / Flores-Campos, Rocío / Pascual-Pasto, Guillem / Robles, María José / Machado, Isidro / Llombart-Bosch, Antonio / Magagnoli, Giovanna / Scotlandi, Katia / Carcaboso, Ángel M / Mora, Jaume / de Álava, Enrique / Hontecillas-Prieto, Lourdes

    Oncogene

    2021  Volume 40, Issue 39, Page(s) 5843–5853

    Abstract: Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and ... ...

    Abstract Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.
    MeSH term(s) Acetylation ; Carcinogenesis ; Histone Deacetylase 6 ; Humans ; Promoter Regions, Genetic ; Proto-Oncogene Protein c-fli-1 ; Sarcoma, Ewing
    Chemical Substances Proto-Oncogene Protein c-fli-1 ; Histone Deacetylase 6 (EC 3.5.1.98)
    Language English
    Publishing date 2021-08-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-021-01974-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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