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  1. AU="Rodríguez-Cobos, J"
  2. AU="Graham, S. Elizabeth"
  3. AU="Piñero, Fernando L"
  4. AU="LUBAN-PLOZZA, B"
  5. AU="Dewitte, Olivier"
  6. AU="Low, Zhen Luan"
  7. AU="Song, Jin-Ju"
  8. AU="Liu-Xia Zhang"
  9. AU="Ahmed, Abdallah M Said"
  10. AU=Hover Alexander R
  11. AU="Zaniar Ghazizadeh"
  12. AU="Rathod, Aniruddha"
  13. AU=Ong Edison
  14. AU="Hoffmann, Daniela"
  15. AU="Mallett, Garry"
  16. AU=Lemos Pedro A
  17. AU="Bakris, George L."
  18. AU="Tun-Linn Thein"
  19. AU="Michelle Schinkel"
  20. AU="Scolieri, G"

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  1. Artikel ; Online: Genomic profiling in oncology clinical practice.

    Rodríguez, N / Viñal, D / Rodríguez-Cobos, J / De Castro, J / Domínguez, G

    Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

    2020  Band 22, Heft 9, Seite(n) 1430–1439

    Abstract: The development of high-throughput technologies such as next-generation sequencing for DNA sequencing together with the decrease in their cost has led to the progressive introduction of genomic profiling in our daily practice in oncology. Nowadays, ... ...

    Abstract The development of high-throughput technologies such as next-generation sequencing for DNA sequencing together with the decrease in their cost has led to the progressive introduction of genomic profiling in our daily practice in oncology. Nowadays, genomic profiling is part of genetic counseling, cancer diagnosis, molecular characterization, and as a biomarker of prognosis and response to treatment. Furthermore, germline or somatic genomic characterization of the tumor may provide new treatment opportunities for patients with cancer. In this review, we will summarize the clinical applications and limitations of genomic profiling in oncology clinical practice, focusing on next-generation sequencing.
    Mesh-Begriff(e) Biomarkers, Tumor/genetics ; Genetic Counseling/methods ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Medical Oncology/methods ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Precision Medicine/methods ; Prognosis
    Chemische Substanzen Biomarkers, Tumor
    Sprache Englisch
    Erscheinungsdatum 2020-01-24
    Erscheinungsland Italy
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2397359-6
    ISSN 1699-3055 ; 1699-048X
    ISSN (online) 1699-3055
    ISSN 1699-048X
    DOI 10.1007/s12094-020-02296-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Vitamin D opposes multilineage cell differentiation induced by Notch inhibition and BMP4 pathway activation in human colon organoids.

    Bustamante-Madrid, Pilar / Barbáchano, Antonio / Albandea-Rodríguez, David / Rodríguez-Cobos, Javier / Rodríguez-Salas, Nuria / Prieto, Isabel / Burgos, Aurora / Martínez de Villarreal, Jaime / Real, Francisco X / González-Sancho, José Manuel / Larriba, María Jesús / Lafarga, Miguel / Muñoz, Alberto / Fernández-Barral, Asunción

    Cell death & disease

    2024  Band 15, Heft 4, Seite(n) 301

    Abstract: Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide an unique tool to address these questions but studies are scarce. We ... ...

    Abstract Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide an unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using colon organoids generated from healthy tissue of colorectal cancer patients. Culture of these organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1, FABP2) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the γ-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 showing only weak signals of cell differentiation, and were unresponsive to DBZ. We also investigated the effects of 1α,25-dihydroxyvitamin D
    Mesh-Begriff(e) Humans ; Organoids/drug effects ; Organoids/metabolism ; Cell Differentiation/drug effects ; Bone Morphogenetic Protein 4/metabolism ; Colon/drug effects ; Colon/metabolism ; Colon/cytology ; Colon/pathology ; Receptors, Notch/metabolism ; Kruppel-Like Factor 4 ; Signal Transduction/drug effects ; Calcitriol/pharmacology ; Goblet Cells/drug effects ; Goblet Cells/metabolism ; Dibenzazepines/pharmacology ; Cell Lineage/drug effects ; Enterocytes/metabolism ; Enterocytes/drug effects ; Enterocytes/cytology ; Vitamin D/pharmacology ; Carrier Proteins
    Chemische Substanzen Bone Morphogenetic Protein 4 ; Receptors, Notch ; dibenzazepine (J411KQJ8C2) ; BMP4 protein, human ; Kruppel-Like Factor 4 ; Calcitriol (FXC9231JVH) ; KLF4 protein, human ; Dibenzazepines ; noggin protein (148294-77-3) ; Vitamin D (1406-16-2) ; Carrier Proteins
    Sprache Englisch
    Erscheinungsdatum 2024-04-29
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06680-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: ΔNp73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells).

    Prieto-Nieto, M I / Pastor, D / Rodríguez-Cobos, J / Pérez, J P / Méndez, C / Palacios, E / Arranz-Alvarez, M / Santos-López, J / Cano-Vega, M / Viñal, D / Rodríguez, N / Domínguez, G

    Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

    2019  Band 21, Heft 10, Seite(n) 1432–1439

    Abstract: Introduction: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3-0.9% of the appendectomies, 35-58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The ... ...

    Abstract Introduction: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3-0.9% of the appendectomies, 35-58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis.
    Materials and methods: We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer.
    Results: Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively.
    Conclusion: Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series.
    Mesh-Begriff(e) Adenocarcinoma/chemistry ; Adenocarcinoma/secondary ; Adenocarcinoma/therapy ; Appendiceal Neoplasms/chemistry ; Appendiceal Neoplasms/pathology ; Appendiceal Neoplasms/therapy ; Biomarkers, Tumor/analysis ; Colon/chemistry ; Colonic Neoplasms/chemistry ; Cytoreduction Surgical Procedures ; Down-Regulation ; Female ; Goblet Cells/chemistry ; Humans ; Hyperthermia, Induced ; Male ; Middle Aged ; Ovarian Neoplasms/chemistry ; Ovarian Neoplasms/secondary ; Peritoneal Neoplasms/chemistry ; Peritoneal Neoplasms/secondary ; Peritoneum/chemistry ; Tumor Protein p73/analysis
    Chemische Substanzen Biomarkers, Tumor ; Tumor Protein p73 ; delta Np73 protein, human
    Sprache Englisch
    Erscheinungsdatum 2019-04-25
    Erscheinungsland Italy
    Dokumenttyp Case Reports ; Journal Article
    ZDB-ID 2397359-6
    ISSN 1699-3055 ; 1699-048X
    ISSN (online) 1699-3055
    ISSN 1699-048X
    DOI 10.1007/s12094-019-02091-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: In-depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer.

    Garranzo-Asensio, María / Rodríguez-Cobos, Javier / San Millán, Coral / Poves, Carmen / Fernández-Aceñero, María Jesús / Pastor-Morate, Daniel / Viñal, David / Montero-Calle, Ana / Solís-Fernández, Guillermo / Ceron, María-Ángeles / Gámez-Chiachio, Manuel / Rodríguez, Nuria / Guzmán-Aránguez, Ana / Barderas, Rodrigo / Domínguez, Gemma

    Molecular oncology

    2022  Band 16, Heft 14, Seite(n) 2672–2692

    Abstract: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Alterations in proteins of the p53-family are a common event in CRC. ΔNp73, a p53-family member, shows oncogenic properties and its ... ...

    Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Alterations in proteins of the p53-family are a common event in CRC. ΔNp73, a p53-family member, shows oncogenic properties and its effectors are largely unknown. We performed an in-depth proteomics characterization of transcriptional control by ∆Np73 of the secretome of human colon cancer cells and validated its clinical potential. The secretome was analyzed using high-density antibody microarrays and stable isotopic metabolic labeling. Validation was performed by semiquantitative PCR, ELISA, dot-blot and western blot analysis. Evaluation of selected effectors was carried out using 60 plasma samples from CRC patients, individuals carrying premalignant colorectal lesions and colonoscopy-negative controls. In total, 51 dysregulated proteins were observed showing at least 1.5-foldchange in expression. We found an important association between the overexpression of ∆Np73 and effectors related to lymphangiogenesis, vasculogenesis and metastasis, such as brain-derived neurotrophic factor (BDNF) and the putative aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (EMAP-II)-vascular endothelial growth factor C-vascular endothelial growth factor receptor 3 axis. We further demonstrated the usefulness of BDNF as a potential CRC biomarker able to discriminate between CRC patients and premalignant individuals from controls with high sensitivity and specificity.
    Mesh-Begriff(e) Brain-Derived Neurotrophic Factor/metabolism ; Colorectal Neoplasms/genetics ; Humans ; Lymphangiogenesis ; Proteomics ; Tumor Suppressor Protein p53 ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor C/metabolism
    Chemische Substanzen Brain-Derived Neurotrophic Factor ; Tumor Suppressor Protein p53 ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C
    Sprache Englisch
    Erscheinungsdatum 2022-06-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13228
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer.

    Rodríguez-Cobos, Javier / Viñal, David / Poves, Carmen / Fernández-Aceñero, María J / Peinado, Héctor / Pastor-Morate, Daniel / Prieto, Mª Isabel / Barderas, Rodrigo / Rodríguez-Salas, Nuria / Domínguez, Gemma

    Cancers

    2021  Band 13, Heft 9

    Abstract: The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late ... ...

    Abstract The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (
    Sprache Englisch
    Erscheinungsdatum 2021-05-07
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13092240
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience.

    Martinez-Perez, Daniel / Viñal, David / Peña-Lopez, Jesús / Jimenez-Bou, Diego / Ruiz-Gutierrez, Iciar / Martinez-Recio, Sergio / Alameda-Guijarro, María / Rueda-Lara, Antonio / Martin-Montalvo, Gema / Ghanem, Ismael / Custodio, Ana Belén / Trilla-Fuertes, Lucia / Gamez-Pozo, Angelo / Barbachano, Antonio / Rodriguez-Cobos, Javier / Bustamante-Madrid, Pilar / Fernandez-Barral, Asuncion / Burgos, Aurora / Prieto-Nieto, Maria Isabel /
    Pastrian, Laura Guerra / González-Sancho, José Manuel / Muñoz, Alberto / Feliu, Jaime / Rodríguez-Salas, Nuria

    Cancers

    2023  Band 15, Heft 17

    Abstract: Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic.: ...

    Abstract Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic.
    Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old.
    Results: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%).
    Conclusions: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.
    Sprache Englisch
    Erscheinungsdatum 2023-08-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15174242
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Relevance of pituitary aromatase and estradiol on the maintenance of the population of prolactin-positive cells in male mice.

    García-Barrado, María José / Blanco, Enrique J / Catalano-Iniesta, Leonardo / Sanchez-Robledo, Virginia / Iglesias-Osma, María Carmen / Carretero-Hernández, Marta / Rodríguez-Cobos, Javier / Burks, Deborah Jane / Carretero, José

    Steroids

    2016  Band 111, Seite(n) 121–126

    Abstract: In previous studies we demonstrated the expression of aromatase in pituitary cells. This expression is gender related, and is also associated with the presence of prolactinomas. To ascertain the relevance of aromatase in modulating the populations of ... ...

    Abstract In previous studies we demonstrated the expression of aromatase in pituitary cells. This expression is gender related, and is also associated with the presence of prolactinomas. To ascertain the relevance of aromatase in modulating the populations of prolactin-positive pituitary cells an immunocytochemical and morphometric study of prolactin-positive pituitary cells was carried out using the pituitary glands of adult male and female aromatase-knockout (ArKO) mice. Additionally has been determined if pituitary aromatase is involved in a gender-linked differentiated regulation of the prolactin-producing pituitary cells. Compared to wild-type mice, the knockout animals of both genders showed a significant decrease (p<0.01) in the cellular and nuclear areas of their prolactin cells, as well as in the percentages of the prolactin-positive cells and the proliferating prolactin cells. Our results suggest that estradiol is responsible for the maintenance of the population of prolactin cell in males and, so as not to disturb the endocrine reproductive environment, estradiol is synthesized inside the pituitary by circulating testosterone via means of aromatase P450, which acts in paracrine way. This new role for pituitary aromatase may well explain the previous findings establishing that the pituitary expression of aromatase is higher in males than in females, and the association between the development of prolactinomas and the increased expression of aromatase in tumours.
    Mesh-Begriff(e) Animals ; Aromatase/genetics ; Aromatase/metabolism ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Estradiol/metabolism ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pituitary Gland/enzymology ; Pituitary Gland/metabolism ; Prolactin/metabolism ; Sex Factors ; Testosterone/metabolism
    Chemische Substanzen Testosterone (3XMK78S47O) ; Estradiol (4TI98Z838E) ; Prolactin (9002-62-4) ; Aromatase (EC 1.14.14.1)
    Sprache Englisch
    Erscheinungsdatum 2016-07
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2016.03.020
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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