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  1. AU="Konstantinos Venetis"
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  1. Article ; Online: Mismatch Repair System Genomic Scars in Gastroesophageal Cancers

    Gianluca Lopez / Konstantinos Venetis / Elham Sajjadi / Nicola Fusco

    Gastrointestinal Disorders, Vol 2, Iss 31, Pp 341-

    Biology and Clinical Testing

    2020  Volume 352

    Abstract: Alterations in the mismatch repair (MMR) system result in genomic instability, neoantigen production, and immune response in cancer. There is evidence that gastroesophageal tumors with MMR deficiency may be susceptible to immune-checkpoint inhibitors ... ...

    Abstract Alterations in the mismatch repair (MMR) system result in genomic instability, neoantigen production, and immune response in cancer. There is evidence that gastroesophageal tumors with MMR deficiency may be susceptible to immune-checkpoint inhibitors treatment, especially in those presenting at advanced-stage disease. Although a number of biomarkers have been developed in histology-agnostic settings to assess MMR status, there is evidence that a tumor-specific testing approach would improve the selection of patients for immunotherapy. However, no testing methods have been developed specifically for gastroesophageal cancers so far. Here, we discuss the state of the art, current advances, and future perspectives of MMR-related biomarkers’ biologic and clinical role in gastroesophageal cancers.
    Keywords mismatch repair ; microsatellite instability ; biomarkers ; immunotherapy gastroesophageal cancer ; gastric cancer ; Medicine ; R ; Diseases of the digestive system. Gastroenterology ; RC799-869
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Pathological identification of HER2-low breast cancer

    Elham Sajjadi / Elena Guerini-Rocco / Elisa De Camilli / Oriana Pala / Giovanni Mazzarol / Konstantinos Venetis / Mariia Ivanova / Nicola Fusco

    Frontiers in Molecular Biosciences, Vol

    Tips, tricks, and troubleshooting for the optimal test

    2023  Volume 10

    Abstract: The introduction of novel anti-HER2 antibody-drug conjugates (ADC) for the treatment of HER2-low breast cancers has transformed the traditional dichotomy of HER2 status to an expanded spectrum. However, the identification of HER2-low (i.e., ... ...

    Abstract The introduction of novel anti-HER2 antibody-drug conjugates (ADC) for the treatment of HER2-low breast cancers has transformed the traditional dichotomy of HER2 status to an expanded spectrum. However, the identification of HER2-low (i.e., immunohistochemistry (IHC) score 1 + or IHC score 2+, without gene amplification) tumors is challenged by methodological and analytical variables that might influence the sensitivity and reproducibility of HER2 testing. To open all possible therapeutic opportunities for HER2-low breast cancer patients the implementation of more accurate and reproducible testing strategies is mandatory. Here, we provide an overview of the existing barriers that may trouble HER2-low identification in breast cancer and discuss practical solutions that could enhance HER-low assessment.
    Keywords breast cancer ; HER2 ; HER2-low ; pathology ; precision medicine ; immunohistochemistry ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Breast Cancer with Bone Metastasis

    Konstantinos Venetis / Roberto Piciotti / Elham Sajjadi / Marco Invernizzi / Stefania Morganti / Carmen Criscitiello / Nicola Fusco

    Cells, Vol 10, Iss 1377, p

    Molecular Insights and Clinical Management

    2021  Volume 1377

    Abstract: Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on ... ...

    Abstract Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.
    Keywords breast cancer ; bone metastasis ; therapy resistance ; tumor progression ; tumor-bone microenvironment ; bone-targeting therapy ; Biology (General) ; QH301-705.5
    Subject code 616 ; 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Physical Exercise with or without Whole-Body Vibration in Breast Cancer Patients Suffering from Aromatase Inhibitor—Induced Musculoskeletal Symptoms

    Alessandro de Sire / Lorenzo Lippi / Antonio Ammendolia / Carlo Cisari / Konstantinos Venetis / Elham Sajjadi / Nicola Fusco / Marco Invernizzi

    Journal of Personalized Medicine, Vol 11, Iss 1369, p

    A Pilot Randomized Clinical Study

    2021  Volume 1369

    Abstract: In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a ... ...

    Abstract In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a history of breast cancer and current AIMSS. Enrolled patients ( n = 22) were randomly assigned 1:1 to receive physical exercise combined with WBV or sham WBV for 4 weeks. The primary endpoint was pain intensity measured by numerical pain rating scale (NPRS). The secondary endpoints were muscle strength, physical function, physical performance, and quality of life. The WBV group (mean age: 51.73 ± 10.73 years; body mass index (BMI): 25.56 ± 5.17 kg/m 2 ) showed a statistically significant pain reduction (NPRS: 6.82 ± 1.17 vs. 5.73 ± 1.01; p = 0.031), whereas patients in the sham WBV group (mean age: 58.55 ± 9.71 years; BMI: 27.31 ± 3.84 kg/m 2 ), did not reach statistical significance (NPRS: 6.91 ± 2.02 vs. 5.91 ± 2.51; p = 0.07). Concurrently, muscle strength, physical performance, and quality of life significantly improved in both groups, without significant differences between groups. No dropouts and no side effects were recorded. Both patients and the physical therapist reported a high level of satisfaction with the intervention. Our findings suggest that physical exercise and WBV combination might be a safe therapeutic option for improving the rehabilitative management of patients with AIMSS.
    Keywords breast cancer ; precision medicine ; aromatase inhibitors ; pain ; physical exercise ; whole-body vibration ; Medicine ; R
    Subject code 796
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs)

    Isabella Piga / Vincenzo L’Imperio / Lucrezia Principi / Claudio Bellevicine / Nicola Fusco / Fausto Maffini / Konstantinos Venetis / Mariia Ivanova / Davide Seminati / Gabriele Casati / Lisa Pagani / Stefania Galimberti / Giulia Capitoli / Mattia Garancini / Andrea-Valer Gatti / Fulvio Magni / Fabio Pagni

    International Journal of Molecular Sciences, Vol 24, Iss 2567, p

    2023  Volume 2567

    Abstract: Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular ... ...

    Abstract Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)–Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs ( n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI–MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z ), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS–MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised.
    Keywords thyroid cancer ; NIFTP ; MALDI–MSI ; proteomics ; NGS ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer

    Elham Sajjadi / Konstantinos Venetis / Marianna Noale / Hatem A. Azim / Concetta Blundo / Giuseppina Bonizzi / Eugenia Di Loreto / Giovanna Scarfone / Stefano Ferrero / Stefania Maggi / Massimo Barberis / Paolo Veronesi / Viviana E. Galimberti / Giuseppe Viale / Nicola Fusco / Fedro A. Peccatori / Elena Guerini-Rocco

    Cells, Vol 11, Iss 2286, p

    Analysis of the Tumor Immune Microenvironment and Risk Profiles

    2022  Volume 2286

    Abstract: Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early- ... ...

    Abstract Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2– breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.
    Keywords breast cancer during pregnancy ; early-onset breast cancer ; pregnancy-related breast cancer ; tumor-infiltrating lymphocytes ; PD-L1 ; tumor microenvironment ; Biology (General) ; QH301-705.5
    Subject code 610 ; 616
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer

    Gianluca Lopez / Marianna Noale / Chiara Corti / Gabriella Gaudioso / Elham Sajjadi / Konstantinos Venetis / Donatella Gambini / Letterio Runza / Jole Costanza / Chiara Pesenti / Francesco Grossi / Stefania Maggi / Stefano Ferrero / Silvano Bosari / Nicola Fusco

    International Journal of Molecular Sciences, Vol 21, Iss 4, p

    2020  Volume 1461

    Abstract: Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite ... ...

    Abstract Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors ( p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.
    Keywords breast cancer ; mismatch repair ; pten ; immunohistochemistry ; biomarkers ; immunotherapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Targeting Immune-Related Biological Processes in Solid Tumors

    Fabio Pagni / Elena Guerini-Rocco / Anne Maria Schultheis / Giulia Grazia / Erika Rijavec / Michele Ghidini / Gianluca Lopez / Konstantinos Venetis / Giorgio Alberto Croci / Umberto Malapelle / Nicola Fusco

    International Journal of Molecular Sciences, Vol 20, Iss 21, p

    We do Need Biomarkers

    2019  Volume 5452

    Abstract: Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of ... ...

    Abstract Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of a single biomarker is somewhat naïve and imprecise, given that immunotherapy does not follow the rules that we have experienced in the past for targeted therapies. On the other hand, additional immune-related biomarkers that are reliable in real-life clinical practice remain to be identified. Recently, the immune-checkpoint blockade has been approved in the US irrespective of the tumor site of origin. Further histology-agnostic approvals, coupled with with tumor-specific companion diagnostics and guidelines, are expected in this field. In addition, immune-related biomarkers can also have a significant prognostic value. In this review, we provide an overview of the role of these biomarkers and their characterization in the management of lung cancer, melanoma, colorectal cancer, gastric cancer, head and neck cancer, renal cell carcinoma, urothelial cancers, and breast cancer.
    Keywords immunotherapy ; immunoediting ; cancer ; biomarkers ; melanoma ; lung cancer ; breast cancer ; head and neck cancer ; gastrointestinal tract cancer ; renal cell carcinoma ; urothelial cancer ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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