Yazar "Vosough, Massoud" seçeneğine göre listele

Listeleniyor 1 - 4 / 4
  • Küçük Resim
    Öğe
    c-FLIP/Ku70 complex; A potential molecular target for apoptosis induction in hepatocellular carcinoma
    (Academic press inc., 2025) Haghir-Sharif-Zamini, Yasamin; Khosravi, Arezoo; Hassan, Moustapha; Zarrabi, Ali; Vosough, Massoud
    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide and the most common form of liver cancer. Despite global efforts toward early diagnosis and effective treatments, HCC is often diagnosed at advanced stages, where conventional therapies frequently lead to resistance and/or high recurrence rates. Therefore, novel biomarkers and promising medications are urgently required. Epi-drugs, or epigenetic-based medicines, have recently emerged as a promising therapeutic modality. Since the epigenome of the cancer cells is always dysregulated and this is followed by apoptosis-resistance, reprogramming the epigenome of cancer cells by epi-drugs (such as HDAC inhibitors (HDACis), and DNMT inhibitors (DNMTis)) could be an alternative approach to use in concert with established treatment protocols. C-FLIP, an anti-apoptotic protein, and Ku70, a member of the DNA repair system, bind together and make a cytoplasmic complex in certain cancers and induce resistance to apoptosis. Many epi-drugs, such as HDACis, can dissociate this complex through Ku70 acetylation and activate cellular apoptosis. The novel compounds for dissociating this complex could provide an innovative insight into molecular targeted HCC treatments. In this review, we address the innovative therapeutic potential of targeting c-FLIP/Ku70 complex by epi-drugs, particularly HDACis, to overcome apoptosis resistance of HCC cells. This review will cover the mechanisms by which the c-FLIP/Ku70 complex facilitates cancer cell survival, the impact of epigenetic alterations on the complex dissociation, and highlight HDACis potential in combination therapies, biomarker developments and mechanistic overviews. This review highlights c-FLIP ubiquitination and Ku70 acetylation levels as diagnostic and prognostic tools in HCC management.
  • Küçük Resim
    Öğe
    Immunotherapeutic approaches in hepatocellular carcinoma: building blocks of hope in near future
    (Elsevier, 2023) Minaei, Neda; Ramezankhani, Roya; Tamimi, Atena; Piryaei, Abbas; Zarrabi, Ali; Aref, Amir Reza; Mostafavi, Ebrahim; Vosough, Massoud
    Hepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications. © 2022 The Authors
  • Küçük Resim Yok
    Öğe
    Machine learning and experimental analyses identified miRNA expression models associated with metastatic osteosarcoma
    (Elsevier, 2024) Abedi, Samira; Behmanesh, Ali; Mazhar, Farid Najd; Bagherifard, Abolfazl; Sami, Sam Hajialiloo; Heidari, Negar; Hossein-Khannazer, Nikoo; Namazifard, Saina; Arki, Mandana Kazem; Shams, Roshanak; Zarrabi, Ali; Vosough, Massoud
    Osteosarcoma (OS), as the most common primary bone cancer, has a high invasiveness and metastatic potential, therefore, it has a poor prognosis. This study identified early diagnostic biomarkers using miRNA expression profiles associated with osteosarcoma metastasis. In the first step, we used RNA-seq and online microarray data from osteosarcoma tissues and cell lines to identify differentially expressed miRNAs. Then, using seven feature selection algorithms for ranking, the first-ranked miRNAs were selected as input for five machine learning systems. Using network analysis and machine learning algorithms, we developed new diagnostic models that successfully differentiated metastatic osteosarcoma from non-metastatic samples based on newly discovered miRNA signatures. The results showed that miR-34c-3p and miR-154-3p act as the most promising models in the diagnosis of metastatic osteosarcoma. Validation for this model by RT-qPCR in benign tissue and osteosarcoma biopsies confirmed the lower expression of miR-34c-3p and miR-154-3p in OS samples. In addition, a direct correlation between miR-34c-3p expression, miR-154-3p expression and tumor grade was discovered. The combined values of miR-34c-3p and miR-154-3p showed 90 % diagnostic power (AUC = 0.90) for osteosarcoma samples and 85 % (AUC = 0.85) for metastatic osteosarcoma. Adhesion junction and focal adhesion pathways, as well as epithelial-to-mesenchymal transition (EMT) GO terms, were identified as the most significant KEGG and GO terms for the top miRNAs. The findings of this study highlight the potential use of novel miRNA expression signatures for early detection of metastatic osteosarcoma. These findings may help in determining therapeutic approaches with a quantitative and faster method of metastasis detection and also be used in the development of targeted molecular therapy for this aggressive cancer. Further research is needed to confirm the clinical utility of miR-34c-3p and miR-154-3p as diagnostic biomarkers for metastatic osteosarcoma.
  • Küçük Resim Yok
    Öğe
    MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells
    (Elsevier B.V., 2024) Seydi, Homeyra; Nouri, Kosar; Shokouhian, Bahare; Piryaei, Abbas; Hassan, Moustapha; Cordani, Marco; Zarrabi, Ali; Shekari, Faezeh; Vosough, Massoud
    Background: In spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. Method: Human Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. Results: EV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway. © 2024 Elsevier B.V.