Publications by authors named "Georgoulias V"

Introduction: mutations are now established as a key mechanism of resistance to endocrine therapy in estrogen-receptor-positive breast cancer (ER​+ ​breast cancer) and their sensitive and specific detection in plasma-cell free DNA (plasma-cfDNA) is crucial to monitor during patient treatment. In the present proof-of-principle study, we evaluated the performance of a novel multiplex assay (12plex) for the detection of ten mutations and E17K in plasma-cfDNA based on Crystal Digital PCR® (Stilla Technologies, France).

Materials & Methods: We analyzed 35 plasma-cfDNA samples from ER+ ​breast cancer patients and 10 samples from healthy donors and further compared the results with our previously reported NAPA assay for D538G, Y537S, Y537C and Y537 N mutations.

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Introduction: The use of taxanes in the adjuvant setting of early breast cancer (BC) confers survival benefits, however, their role in older patients merits further study. This retrospective pooled analysis of randomized controlled trials conducted by the Hellenic Oncology Research Group (HORG) aims to assess the efficacy and safety of taxane-based adjuvant chemotherapy in older women with BC.

Materials And Methods: Five phase III trials containing a taxane, conducted by HORG between 1995 and 2013, were included in a patient-data pooled analysis.

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Background: The treatment landscape of non-metastatic non-small cell lung cancer (NM-NSCLC) is rapidly evolving with recent approvals of immunotherapies and targeted therapies.

Methods: This retrospective study included 202 adults diagnosed with NM-NSCLC between 1 January 2018 and 31 December 2020 primarily aiming to capture initial management strategies.

Results: Most frequent treatment patterns among Stage I/II patients ( = 84) were surgery only (48.

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Liquid biopsy enables real-time monitoring of tumor development and response to therapy through the analysis of CTCs and ctDNA. NALCN is a sodium leak channel that is frequently involved in tumor evolution and immunity and acts as a tumor suppressor. Deletion of NALCN has been shown to increase cancer metastasis and the number of CTCs in peripheral blood.

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PARP inhibitors (PARPi) have shown efficacy in tumours harbouring mutations in homologous recombination repair (HRR) genes. Somatic HRR mutations have been described in patients with Non-Small Cell Lung Cancer (NSCLC), but PARP inhibitors (PARPi) are not yet a therapeutic option. Here we assessed the homologous recombination status of early-stage NSCLC and explored the therapeutic benefit of PARPi in preclinical models.

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Article Synopsis
  • Lung cancer is a major global health issue, with challenges in early detection and relapse identification; blood-based liquid biopsies show potential in non-invasive monitoring.
  • Researchers used a comprehensive approach combining various datasets to identify candidate biomarkers in non-small cell lung cancer (NSCLC), connecting them to specific molecular pathways.
  • Results indicated that certain metabolites and RNA expressions in plasma EVs correlate with disease progression and overall survival in NSCLC patients, highlighting their potential as prognostic biomarkers.
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The increased metastatic ability of small-cell lung cancer (SCLC) necessitates the identification of new prognostic biomarkers for clinical evaluation during the disease course. Our previous research highlighted the clinical relevance of transcription factor JunB (JUNB), C-X-C chemokine receptor type 4 (CXCR4), and programmed cell death 1 ligand 1 (PD-L1) in breast and non-small cell lung cancer (NSCLC) patients. In the current study, we examined these biomarkers in circulating tumor cells (CTCs) and plasma-derived exosomes from 100 treatment-naïve SCLC patients.

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  • The study investigates the genetic landscape of non-small cell lung cancer (NSCLC) and its impact on resistance to osimertinib, using liquid biopsy to identify resistance mechanisms.
  • It analyzed plasma-circulating free DNA (cfDNA) and circulating tumor cells (CTCs) from 30 NSCLC patients, detecting various molecular alterations that could indicate resistance to treatment.
  • Findings revealed discrepancies in the mutation presence between cfDNA and CTCs, suggesting that combining both analyses provides a broader understanding of resistance and potential treatment options.
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  • The study presents a new liquid bead array assay that detects specific mutations in circulating tumor cells (CTCs) from metastatic breast cancer (MBC) patients, which can help identify tumor progression and therapy resistance.
  • The assay utilizes advanced techniques like enzymatic mutation enrichment and multiplex PCR, allowing for highly sensitive (0.1% mutation detection limit) and specific identification of mutations in single CTCs.
  • Validation of the assay showed that it can analyze 96 single cells at once, making it both efficient and sample-conserving, thereby providing crucial insights into the genetic landscape of tumors.
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  • * A study involving 52 stage III/IV NSCLC patients showed that 44% had detectable pre-existing T cells specific to tumors, and those patients had better median overall survival rates compared to those without these T cells.
  • * The research highlighted that patients with pre-existing T cells and low levels of certain immunosuppressive cells had a significant survival advantage, suggesting that evaluating these immune cell characteristics could help identify which patients are likely to benefit most from immunotherapy.
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Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment.

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To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAF mutations were evaluated by Sanger sequencing.

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CXCR4, JUNB and PD-L1 are implicated in cancer progression and metastasis. The current study investigated these biomarkers in CTCs isolated from metastatic prostate cancer (mPCa) patients at the RNA and protein levels. CTCs were isolated from 48 mPCa patients using the Ficoll density gradient and ISET system (17 out of 48).

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Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included.

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Therapeutic management of NSCLC patients is quite challenging as they are mainly diagnosed at a late stage of disease, and they present a high heterogeneous molecular profile. Osimertinib changed the paradigm shift in treatment of mutant NSCLC patients achieving significantly better clinical outcomes. To date, osimertinib is successfully administered not only as first- or second-line treatment, but also as adjuvant treatment while its efficacy is currently investigated during neoadjuvant treatment or in stage III, unresectable mutant NSCLC patients.

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  • The study investigated the clinical significance of circulating tumor cells (CTCs) in patients with metastatic castration-resistant prostate cancer (mCRPC) who were receiving cabazitaxel treatment.
  • Results showed that a high number of CTCs detected at baseline and after the first treatment cycle were linked to shorter progression-free survival (PFS) and overall survival (OS).
  • The presence of non-apoptotic CTCs at baseline was identified as an independent predictor of poorer OS, suggesting that monitoring CTCs could help gauge treatment effectiveness and patient prognosis.
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Breast cancer is the leading cause of cancer-related deaths in women worldwide. Approximately 40% of patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer have activating mutations in the gene. We developed a highly sensitive, specific, cost-effective, and reproducible dual-drop-off droplet digital polymerase chain reaction (PCR) assay for the simultaneous detection of ten hotspots of mutations in plasma cell-free (cf) DNA.

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  • Metastasis is responsible for around 90% of breast cancer deaths, with microtentacles (McTNs) playing a key role in this process, particularly in the aggressive triple-negative breast cancer (TNBC) subtype which lacks effective targeted therapies.
  • The study focused on isolating viable circulating tumor cells (CTCs) from 20 TNBC patients to assess their response to the drug vinorelbine, finding that this treatment led to a significant increase in CTC numbers and induced apoptosis in these cancer cells.
  • Results indicated that vinorelbine not only triggered cell death but also decreased specific markers (like PD-L1) and disrupted McTNs, highlighting a promising method
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  • The study aimed to gather real-world data on the EGFR mutational profile and treatment strategies for advanced non-small-cell lung cancer (NSCLC) patients after first/second-generation EGFR-TKI treatment.
  • Ninety-six patients were enrolled in Greece, with re-biopsies conducted for some who were negative for the T790M mutation.
  • Results showed that 21.9% of patients were T790M-positive, and those receiving third-generation EGFR-TKIs had better outcomes, highlighting the importance of mutational status and treatment choices in improving response rates and progression-free survival.
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Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. There are few targeted therapies for these patients, leading to an unmet need for new biomarkers. The present study aimed to investigate the expression of PD-L1, CTLA-4, GLU, and VIM in CTCs of TNBC patients.

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Purpose: We assessed whether preoperativemutational analyses of circulating tumor cells (CTCs) and plasma-cfDNA could be used as minimally invasive biomarkers and as complimentary tools for early prediction of relapse in early-stage non-small -cell lung cancer (NSCLC).

Experimental Design: Using ddPCR assays, hotspot mutations of and were identified in plasma-cfDNA samples and size-based enriched CTCs isolated from the same blood samples of 49 early-stage NSCLC patients before surgery and in a control group of healthy blood donors (= 22). Direct concordance of the mutational spectrum was further evaluated in 27 patient-matched plasma-cfDNA and CTC-derived DNA in comparison to tissue-derived DNA.

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Liquid biopsy (LB) provides a unique minimally invasive tool to follow-up cancer patients over time, to detect minimal residual disease (MRD), to study metastasis-biology and mechanisms of therapy-resistance. Molecular characterization of CTCs offers additionally the potential to understand resistance to therapy and implement individualized targeted treatments which can be modified during the disease evolution and follow-up period of a patient. In this study, we present a long-term follow-up of operable breast cancer patients based on a comprehensive liquid biopsy analysis.

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  • * Researchers analyzed genetic data from 100 Greek men diagnosed with MBC between 1995-2015, examining BRCA1, BRCA2, and 43 other cancer-related genes.
  • * They found pathogenic variants in 13 patients, confirming BRCA2 as the primary genetic risk factor for MBC, while other genes had minimal involvement, complicating the assessment of their collective impact.
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(1) Background: Although spatial statistics are often used by cancer epidemiologists, there is not yet an established collection of methods to serve their needs. We aimed to develop an evidence-based cancer-oriented conceptual collection of methods for spatial analysis; (2) Methods: A triangulation of approaches was used; literature review, consensus meetings (expert panel), and testing the selected methods on "training" databases. The literature review was conducted in three databases.

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  • This study is the first of its kind in Greece, analyzing lung cancer trends and risk factors before and after the economic crisis, particularly focusing on identifying high-risk areas.
  • Data was collected from 5057 lung cancer cases in Crete, comparing incidence and mortality rates between two periods (1992-2008 and 2009-2013), while also considering factors like comorbidity, deprivation, and outdoor air pollution.
  • The results show a significant increase in lung cancer incidence and mortality rates during the economic crisis, especially among smokers and in deprived regions, highlighting the need for targeted interventions for vulnerable populations.
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