Yazar "Deldar Abad Paskeh, Mahshid" seçeneğine göre listele

Listeleniyor 1 - 3 / 3
  • Küçük Resim
    Öğe
    Overcoming doxorubicin resistance in cancer: siRNA-loaded nanoarchitectures for cancer gene therapy
    (2022) Deldar Abad Paskeh, Mahshid; Saebfar, Hamidreza; Mahabady, Mahmood Khaksary; Orouei, Sima; Hushmandi, Kiavash; Zarrabi, Ali
    Gene therapy can be used as a cancer therapy by affecting signaling networks participating in the aggressive behavior of tumors. Small interfering RNA (siRNA) is a genetic tool employed for gene silencing. The siRNA molecules have a length of 21-22 nucleotides, and are synthetic, short non-coding RNAs. The siRNA molecule should be loaded into the RISC complex to carry out its function to degrade mRNA and reduce protein expression. By targeting oncogenic pathways, siRNA can also promote chemosensitivity and reduce resistance. Doxorubicin (DOX) is an anthracycline family member capable of triggering cell cycle arrest via binding to topoisomerase II and inhibiting DNA replication. The present review focuses on the design of siRNA for increasing DOX sensitivity and overcoming resistance. Molecular pathways such as STAT3, Notch1, Mcl-1 and Nrf2 can be down-regulated by siRNA to promote DOX sensitivity. Furthermore, siRNA can be used to suppress the activity of P-glycoprotein as a cell membrane transporter of drugs, leading to enhanced accumulation of DOX. The co-delivery of DOX and siRNA both incorporated into nanoparticles can increase the intracellular accumulation in cancer cells, and protect siRNA against degradation by enzymes. Furthermore, the circulation time of DOX is lengthened to boost cytotoxicity against cancer cells. The surface modification of nanocarriers with ligands such as RGD or folate increases their selectivity towards cancer cells. Moreover, smart nanostructures, including pH-, redox- and light-responsive are optimized for siRNA and DOX delivery and tumor treatment.
  • Küçük Resim
    Öğe
    Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response
    (2022) Ashrafizadeh, Milad; Deldar Abad Paskeh, Mahshid; Mirzaei, Sepideh; Gholami, Mohammad Hossein; Zarrabi, Ali
    Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.
  • Küçük Resim
    Öğe
    Wnt/?-Catenin signaling as a driver of hepatocellular carcinoma progression: an emphasis on molecular pathways
    (Dove Medical Press, 2021) Deldar Abad Paskeh, Mahshid; Mirzaei, Sepideh; Ashrafizadeh, Milad; Zarrabi, Ali; Sethi, Gautam
    Liver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains a challenging disease to treat. Wnt/?-catenin signaling pathway is considered a tumor-promoting factor in various cancers; hence, the present review focused on the role of Wnt signaling in HCC, and its association with progression and therapy response based on pre-clinical and clinical evidence. The nuclear translocation of ?-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding ?-catenin and its overexpression can lead to HCC progression. ?-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, ?-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that ?-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate ?-catenin signaling in HCC. Anti-cancer agents inhibit ?-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of ?-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/?-catenin signaling in HCC therapy.