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  1. Article: microRNAs in Liquid Biopsy: The Way to a Simple and Rapid Test for Early Colorectal Cancer Diagnosis?

    Matis, Serena / Poggi, Alessandro / Benelli, Roberto

    Cancers

    2023  Volume 15, Issue 3

    Abstract: About 15% of colorectal cancers (CRCs) are diagnosed as advanced, metastatic stage IV, a patient condition with an average survival of 2 [ ... ]. ...

    Abstract About 15% of colorectal cancers (CRCs) are diagnosed as advanced, metastatic stage IV, a patient condition with an average survival of 2 [...].
    Language English
    Publishing date 2023-01-28
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15030797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Pleiotropic Effects of Gut Microbiota in Colorectal Cancer Progression: How to Turn Foes into Friends.

    Tardito, Samuele / Matis, Serena / Benelli, Roberto

    Cancers

    2023  Volume 15, Issue 3

    Abstract: Colorectal Cancer (CRC) is one of most frequent malignant cancers, showing high lethality worldwide [ ... ]. ...

    Abstract Colorectal Cancer (CRC) is one of most frequent malignant cancers, showing high lethality worldwide [...].
    Language English
    Publishing date 2023-02-01
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15030916
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Immune Checkpoint Receptor/Ligand Expression and Chemotherapy in Colorectal Cancer.

    Benelli, Roberto / Zocchi, Maria Raffaella / Poggi, Alessandro

    Cancers

    2023  Volume 15, Issue 3

    Abstract: Immune checkpoint (IC) molecules act as receptors, expressed on immune effector cells, that are able to recognize specific ligands in normal or tumor cells [ ... ]. ...

    Abstract Immune checkpoint (IC) molecules act as receptors, expressed on immune effector cells, that are able to recognize specific ligands in normal or tumor cells [...].
    Language English
    Publishing date 2023-02-01
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15030914
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Stockholm Syndrome of Cancer: Fibroblasts as a Powerful Shield against Colorectal Cancer Therapy.

    Tardito, Samuele / Zocchi, Maria Raffaella / Benelli, Roberto

    Cancers

    2023  Volume 15, Issue 2

    Abstract: Fibroblasts are incredible cells [ ... ]. ...

    Abstract Fibroblasts are incredible cells [...].
    Language English
    Publishing date 2023-01-13
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15020491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Evolution of 3D Cultures: Toward Tailored Preclinical Models.

    Benelli, Roberto / Zocchi, Maria Raffaella / Poggi, Alessandro

    Cancers

    2023  Volume 15, Issue 2

    Abstract: The identification and validation of simple, reliable and reproducible three dimensional (3D) in vitro culture systems represent a major challenge in the field of anticancer drug development [ ... ]. ...

    Abstract The identification and validation of simple, reliable and reproducible three dimensional (3D) in vitro culture systems represent a major challenge in the field of anticancer drug development [...].
    Language English
    Publishing date 2023-01-14
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15020515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: EGFR-Targeted Antibody-Drug Conjugate to Different Aminobisphosphonates: Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells.

    Pisheh, Leila / Matis, Serena / Taglieri, Martina / Di Gregorio, Linda / Benelli, Roberto / Poggi, Alessandro

    Cancers

    2024  Volume 16, Issue 7

    Abstract: Antibody--drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a "biological missile" ... ...

    Abstract Antibody--drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a "biological missile" that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect.
    Language English
    Publishing date 2024-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16071256
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The In Vitro Adaptation of Patient-Derived Organoids Suggests Alternative Strategies against CMS1 Colorectal Cancer: When the Microenvironment Does Make the Difference.

    Poggi, Alessandro / Matis, Serena / Benelli, Roberto

    Cancers

    2022  Volume 14, Issue 24

    Abstract: Colorectal cancer (CRC) is a relatively slow-growing tumor that can be treated successfully when identified in the early stages [ ... ]. ...

    Abstract Colorectal cancer (CRC) is a relatively slow-growing tumor that can be treated successfully when identified in the early stages [...].
    Language English
    Publishing date 2022-12-10
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14246086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Three-Dimensional (3D) Culture Models in Cancer Investigation, Drug Testing and Immune Response Evaluation.

    Benelli, Roberto / Zocchi, Maria Raffaella / Poggi, Alessandro

    International journal of molecular sciences

    2020  Volume 22, Issue 1

    Abstract: Preclinical models for the definition of anti-cancer drug safety and efficacy are constantly evolving [ ... ]. ...

    Abstract Preclinical models for the definition of anti-cancer drug safety and efficacy are constantly evolving [...].
    MeSH term(s) Antineoplastic Agents/pharmacology ; Cell Culture Techniques ; Drug Evaluation, Preclinical/methods ; Humans ; Immunity/drug effects ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2020-12-25
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22010150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Priming of Colorectal Tumor-Associated Fibroblasts with Zoledronic Acid Conjugated to the Anti-Epidermal Growth Factor Receptor Antibody Cetuximab Elicits Anti-Tumor Vδ2 T Lymphocytes.

    Fernandez, Jordi Leonardo Castrillo / Benelli, Roberto / Costa, Delfina / Campioli, Alessio / Tavella, Sara / Zocchi, Maria Raffaella / Poggi, Alessandro

    Cancers

    2023  Volume 15, Issue 3

    Abstract: Tumor-associated fibroblasts (TAF) exert immunosuppressive effects in colorectal carcinoma (CRC), impairing the recognition of tumor cells by effector lymphocytes, including Vδ2 T cells. Herein, we show that CRC-derived TAF can be turned by zoledronic ... ...

    Abstract Tumor-associated fibroblasts (TAF) exert immunosuppressive effects in colorectal carcinoma (CRC), impairing the recognition of tumor cells by effector lymphocytes, including Vδ2 T cells. Herein, we show that CRC-derived TAF can be turned by zoledronic acid (ZA), in soluble form or as antibody-drug conjugate (ADC), into efficient stimulators of Vδ2 T cells. CRC-TAF, obtained from patients, express the epidermal growth factor receptor (EGFR) and the butyrophilin family members BTN3A1/BTN2A1. These butyrophilins mediate the presentation of the phosphoantigens, accumulated in the cells due to ZA effect, to Vδ2 T cells. CRC-TAF exposed to soluble ZA acquired the ability to trigger the proliferation of Vδ2 T cells, in part represented by effector memory cells lacking CD45RA and CD27. In turn, expanded Vδ2 T cells exerted relevant cytotoxic activity towards CRC cells and CRC-TAF when primed with soluble ZA. Of note, also the ADC made of the anti-EGFR cetuximab (Cet) and ZA (Cet-ZA), that we recently described, induced the proliferation of anti-tumor Vδ2 T lymphocytes and their activation against CRC-TAF. These findings indicate that ZA can educate TAF to stimulate effector memory Vδ2 T cells; the Cet-ZA ADC formulation can lead to the precise delivery of ZA to EGFR
    Language English
    Publishing date 2023-01-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15030610
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation.

    Costa, Delfina / Venè, Roberta / Coco, Simona / Longo, Luca / Tosetti, Francesca / Scabini, Stefano / Mastracci, Luca / Grillo, Federica / Poggi, Alessandro / Benelli, Roberto

    Cells

    2023  Volume 12, Issue 4

    Abstract: The p38 inhibitor SB202190 is a necessary component of the medium used for normal colorectal mucosa cultures. Sato et al. suggested that the primary activity of SB202190 may be EGFR signaling stabilization, causing an increased phosphorylation of Erk1-2 ... ...

    Abstract The p38 inhibitor SB202190 is a necessary component of the medium used for normal colorectal mucosa cultures. Sato et al. suggested that the primary activity of SB202190 may be EGFR signaling stabilization, causing an increased phosphorylation of Erk1-2 sustaining organoid proliferation. However, the growth of some colorectal cancer (CRC)-derived organoid cultures is inhibited by this molecule via an unknown mechanism. We biochemically investigated SB202190 activity on a collection of 25 primary human CRC organoids, evaluating EGFR, Akt and Erk1-2 activation using Western blot. We found that Erk1-2 phosphorylation was induced by SB202190 in 20 organoid cultures and inhibited in 5 organoid cultures. A next-generation sequencing (NGS) analysis revealed that the inhibition of p-Erk1-2 signaling corresponded to the cultures with BRAF mutations (with four different hits, one being undescribed), while p-Erk1-2 induction was apparently unrelated to other mutations involving the EGFR pathway (Her2, KRAS and NRAS). We found that SB202190 mirrored the biochemical activity of the BRAF inhibitor Dabrafenib, known to induce the paradoxical activation of p-Erk1-2 signaling in BRAF wild-type cells. SB202190 was a more effective inhibitor of BRAF-mutated organoid growth in the long term than the specific BRAF inhibitors Dabrafenib and PLX8394. Overall, SB202190 can predict BRAF-activating mutations in patient-derived organoids, as well as allowing for the identification of new BRAF variants, preceding and enforcing NGS data.
    MeSH term(s) Humans ; Proto-Oncogene Proteins B-raf/genetics ; Protein Kinase Inhibitors/pharmacology ; Mutation ; Colorectal Neoplasms/genetics ; ErbB Receptors/genetics ; Organoids/metabolism
    Chemical Substances dabrafenib (QGP4HA4G1B) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole (PVX798P8GI) ; Protein Kinase Inhibitors ; ErbB Receptors (EC 2.7.10.1) ; BRAF protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2023-02-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12040664
    Database MEDical Literature Analysis and Retrieval System OnLINE

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