18 research outputs found
Determination of mutetions in the BRCA2 gene in greek patients with familial breast cancer
No full textFamily history is a well-recognized risk factor for the development of breast cancer. The isolation of BRCA1 and BRCA2 genes, the two major predisposing genes in familial and to early onset breast and ovarian cancer, has resulted to the identification of a large number of families with mutations in these two genes. Despite the large number of distinct mutations, detected in both genes, several mutations have been found to recur in unrelated families of diverse geographical origin. We have analyzed 27 Greek patients with familial breast cancer the majority of those having one first and one second degree relatives affected and 28 patients with sporadic breast cancer for BRCA2 germline mutations. The techniques used were single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Furthermore the clinical presentation and prognosis of BRCA2 associated breast cancer cases was compared to 20 adequately matched for age and date of diagnosis (within one year) sporadic breast cancer patients. We identified three novel (3058delA, 6024delTA and 4147delG) in the ovarian cancer cluster region (OCCR) and one already known (2024del5) germline BRCA2 gene mutations in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CΙ: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group.Το οικογενειακό ιστορικό είναι ένας σημαντικός παράγοντας κινδύνου για την ανάπτυξη του καρκίνου του μαστού. Η απομόνωση των γονιδίων BRCA1 και BRCA2, των δύο κύριων προδιαθεσικών γονιδίων του οικογενούς, του πρώιμου καρκίνου του μαστού, καθώς και του καρκίνου των ωοθηκών, είχε σαν αποτέλεσμα την αναγνώριση μεγάλου αριθμού οικογενειών με μεταλλάξεις στα γονίδια αυτά. Αναλύσαμε 27 Έλληνες ασθενείς με οικογενή καρκίνο του μαστού. Η πλειοψηφία των ασθενών αυτών είχε τουλάχιστον έναν πρώτου και ένα δευτέρου βαθμού συγγενή με τη νόσο για μεταλλάξεις στο γονίδιο BRCA2. Μελετήσαμε ακόμα 28 ασθενείς με σποραδικό καρκίνο του μαστού. Οι τεχνικές που χρησιμοποιήθηκαν ήταν η ανάλυση της διαμόρφωσης της μονής έλικας του DNA (SSCP) και η απευθείας ανάλυση της αλληλουχίας των νουκλεοτιδίων (Sequencing). Επιπλέον η κλινική παρουσίαση και πρόγνωση των περιπτώσεων του καρκίνου του μαστού που συνδέονταν με μεταλλάξεις στο γονίδιο BRCA2, συγκρίθηκε με 20 επαρκώς αντίστοιχους για ηλικία και ημερομηνία διάγνωσης της νόσου ασθενείς (ομάδα ελέγχου), με σποραδικό καρκίνο του μαστού. Αναγνωρίσαμε τρεις καινούριες μεταλλάξεις (3058delA, 6024delTA και 4147delG) στην περιοχή που συνδέεται με καρκίνο των ωοθηκών (OCCR) και μία γνωστή (2024del5), στο γονίδιο BRCA2 σε πέντε διαφορετικές οικογένειες με καρκίνο του μαστού. Η μετάλλαξη 4147delG ανιχνεύθηκε σε δύο μη συγγενείς ασθενείς. Οι μεταλλάξεις στο γονίδιο BRCA2 συνδέονταν με πρώιμο καρκίνο του μαστού RR=4.77 (95% CΙ: 0.666-34.463). Οι ασθενείς με μεταλλάξεις στο γονίδιο BRCA2 δεν παρουσίασαν διαφορετικό ιστολογικό φαινότυπο ωστόσο είχαν βελτιωμένη συνολική επιβίωση (100% vs 65%). Τα ευρήματα μας συνιστούν ότι υπάρχει μία ομάδα νέων μεταλλάξεων στα εξόνια 10 και 11 σε Έλληνες ασθενείς με οικογενή καρκίνο του μαστού. Οι μεταλλάξεις αυτές παρουσίασαν ηπιότερο κλινικό φαινότυπο σε σύγκριση με τους υπόλοιπους ασθενείς που μελετήθηκαν
Liquid Biopsies, Novel Approaches and Future Directions
No full textCancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients’ outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages
Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells
No full textThis review offers a comprehensive exploration of the intricate immunological landscape of breast cancer (BC), focusing on recent advances in diagnosis and prognosis through the analysis of circulating tumor cells (CTCs). Positioned within the broader context of BC research, it underscores the pivotal role of the immune system in shaping the disease’s progression. The primary objective of this investigation is to synthesize current knowledge on the immunological aspects of BC, with a particular emphasis on the diagnostic and prognostic potential offered by CTCs. This review adopts a thorough examination of the relevant literature, incorporating recent breakthroughs in the field. The methodology section succinctly outlines the approach, with a specific focus on CTC analysis and its implications for BC diagnosis and prognosis. Through this review, insights into the dynamic interplay between the immune system and BC are highlighted, with a specific emphasis on the role of CTCs in advancing diagnostic methodologies and refining prognostic assessments. Furthermore, this review presents objective and substantiated results, contributing to a deeper understanding of the immunological complexity in BC. In conclusion, this investigation underscores the significance of exploring the immunological profile of BC patients, providing valuable insights into novel advances in diagnosis and prognosis through the utilization of CTCs. The objective presentation of findings emphasizes the crucial role of the immune system in BC dynamics, thereby opening avenues for enhanced clinical management strategies
The Genetic and Biological Basis of Pseudoarthrosis in Fractures: Current Understanding and Future Directions
No full textPseudoarthrosis—the failure of normal fracture healing—remains a significant orthopedic challenge affecting approximately 10–15% of long bone fractures, and is associated with significant pain, prolonged disability, and repeated surgical interventions. Despite extensive research into the pathophysiological mechanisms of bone healing, diagnostic approaches remain reliant on clinical findings and radiographic evaluations, with little innovation in tools to predict or diagnose non-union. The present review evaluates the current understanding of the genetic and biological basis of pseudoarthrosis and highlights future research directions. Recent studies have highlighted the potential of specific molecules and genetic markers to serve as predictors of unsuccessful fracture healing. Alterations in mesenchymal stromal cell (MSC) function, including diminished osteogenic potential and increased cellular senescence, are central to pseudoarthrosis pathogenesis. Molecular analyses reveal suppressed bone morphogenetic protein (BMP) signaling and elevated levels of its inhibitors, such as Noggin and Gremlin, which impair bone regeneration. Genetic studies have uncovered polymorphisms in BMP, matrix metalloproteinase (MMP), and Wnt signaling pathways, suggesting a genetic predisposition to non-union. Additionally, the biological differences between atrophic and hypertrophic pseudoarthrosis, including variations in vascularity and inflammatory responses, emphasize the need for targeted approaches to management. Emerging biomarkers, such as circulating microRNAs (miRNAs), cytokine profiles, blood-derived MSCs, and other markers (B7-1 and PlGF-1), have the potential to contribute to early detection of at-risk patients and personalized therapeutic approaches. Advancing our understanding of the genetic and biological underpinnings of pseudoarthrosis is essential for the development of innovative diagnostic tools and therapeutic strategies
Unveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers
No full textBreast cancer (BC), one of the most widespread and devastating diseases affecting women worldwide, presents a significant public health challenge. This review explores the emerging frontiers of research focused on deciphering the intricate interplay between BC cells and the immune microenvironment. Understanding the role of the immune system in BC is critical as it holds promise for novel therapeutic approaches and precision medicine strategies. This review delves into the current literature regarding the immune microenvironment’s contribution to BC initiation, progression, and metastasis. It examines the complex mechanisms by which BC cells interact with various immune cell populations, including tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Furthermore, this review highlights the impact of immune-related factors, such as cytokines and immune checkpoint molecules. Additionally, this comprehensive analysis sheds light on the potential biomarkers associated with the immune response in BC, enabling early diagnosis and prognostic assessment. The therapeutic implications of targeting the immune microenvironment are also explored, encompassing immunotherapeutic strategies and combination therapies to enhance treatment efficacy. The significance of this review lies in its potential to pave the way for novel therapeutic interventions, providing clinicians and researchers with essential knowledge to design targeted and personalized treatment regimens for BC patients
Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer
No full textInsulin-like Growth Factor-1 (IGF-1) is a crucial mitogenic factor with important functions in the mammary gland, mainly through its interaction with the IGF-1 receptor (IGF-1R). This interaction activates a complex signaling network that promotes cell proliferation, epithelial to mesenchymal transition (EMT) and inhibits apoptosis. Despite extensive research, the precise molecular pathways and intracellular mechanisms activated by IGF-1, in cancer, remain poorly understood. Recent evidence highlights the essential roles of IGF-1 and its isoforms in breast cancer (BC) development, progression, and metastasis. The peptides that define the IGF-1 isoforms—IGF-1Ea, IGF-1Eb, and IGF-1Ec—act as key points of convergence for various signaling pathways that influence the growth, metastasis and survival of BC cells. The aim of this review is to provide a detailed exami-nation of the role of the mature IGF-1 and its isoforms in BC biology and their potential use as possible therapeutical targets
Immune System and Hepatocellular Carcinoma (HCC): New Insights into HCC Progression
No full textAccording to the WHO’s recently released worldwide cancer data for 2020, liver cancer ranks sixth in morbidity and third in mortality among all malignancies. Hepatocellular carcinoma (HCC), the most common kind of liver cancer, accounts approximately for 80% of all primary liver malignancies and is one of the leading causes of death globally. The intractable tumor microenvironment plays an important role in the development and progression of HCC and is one of three major unresolved issues in clinical practice (cancer recurrence, fatal metastasis, and the refractory tumor microenvironment). Despite significant advances, improved molecular and cellular characterization of the tumor microenvironment is still required since it plays an important role in the genesis and progression of HCC. The purpose of this review is to present an overview of the HCC immune microenvironment, distinct cellular constituents, current therapies, and potential immunotherapy methods
Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer
No full textInsulin-like Growth Factor-1 (IGF-1) is a crucial mitogenic factor with important functions in the mammary gland, mainly through its interaction with the IGF-1 receptor (IGF-1R). This interaction activates a complex signaling network that promotes cell proliferation, epithelial to mesenchymal transition (EMT) and inhibits apoptosis. Despite extensive research, the precise molecular pathways and intracellular mechanisms activated by IGF-1, in cancer, remain poorly understood. Recent evidence highlights the essential roles of IGF-1 and its isoforms in breast cancer (BC) development, progression, and metastasis. The peptides that define the IGF-1 isoforms—IGF-1Ea, IGF-1Eb, and IGF-1Ec—act as key points of convergence for various signaling pathways that influence the growth, metastasis and survival of BC cells. The aim of this review is to provide a detailed exami-nation of the role of the mature IGF-1 and its isoforms in BC biology and their potential use as possible therapeutical targets. © 2024 by the authors
Evidence for the possible biological significance of the igf-1 gene alternative splicing in prostate cancer
No full textInsulin-like growth factor I (IGF-I) has been implicated in the pathogenesis of prostate cancer (PCa), since it plays a key role in cell proliferation, differentiation and apoptosis. The IGF-I actions are mediated mainly via its binding to the type I IGF receptor (IGF-IR), however IGF-I signaling via insulin receptor (IR) and hybrid IGF-I/IR is also evident. Different IGF-I mRNA splice variants, namely IGF-IEa, IGF-IEb and IGF-IEc, are expressed in human cells and tissues. These transcripts encode several IGF-I precursor proteins which contain the same bioactive product (mature IGF-I), however, they differ by the length of their signal peptides on the amino-terminal end and the structure of the extension peptides (E-peptides) on the carboxy-terminal end. There is an increasing interest in the possible different role of the IGF-I transcripts and their respective non-(mature)IGF-I products in the regulation of distinct biological activities. Moreover, there is strong evidence of a differential expression profile of the IGF-I splice variants in normal vs. PCa tissues and PCa cells, implying that the expression pattern of the various IGF-I transcripts and their respective protein products may possess different functions in cancer biology. Herein, the evidence that the IGF-IEc transcript regulates PCa growth via Ec-peptide specific and IGF-IR/IR-independent signaling is discussed
