Biochemistry
Morteza Hassandokht Mashhadi; Fahimeh Taheri; Sadaf Irani; Arshiya Mesbah Mousavi; Ali Mehri; Hossein Javid
Abstract
The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10–30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that the inhibition of proprotein convertase subtilisin/Kexin ...
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The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10–30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that the inhibition of proprotein convertase subtilisin/Kexin type 9 (PCSK9), which plays a critical role in regulating cholesterol metabolism, can cause T cells to move toward tumors, with increased sensitivity to immune checkpoint therapies.We searched PubMed, NCBI, Scopus, and Google Scholar for the published articles without limitations on publication dates. We used the following terms: “PCSK9”, “Cancer”, “Immune Checkpoint”, and “Cancer Prognosis” in the title and/or abstract. Our search initially revealed 600 records on the subject and stored them in the used databases under EndNote X8 management software. We selected about 161 articles that were carefully read and among them, 76 were included in our research.We concluded that PCSK9 reduces the number of LDL receptors (LDL-R) on the cell surface, which is linked to its ability to regulate cholesterol levels in the body. Also, we discuss how suppressing PCSK9 leads to the MHC-1 accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK9 may be an effective strategy for improving cancer immunotherapy.
Neuropathology
Roshanak Ghaffarian Zirak; Hurie Tajik; Jahanbakhsh Asadi; Pedram Hashemian; Hossein Javid
Abstract
Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been ...
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Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been introduced as a novel target for treating glioblastoma via regulation of apoptotic signaling pathway, remarkably PI3K/AKT, which affect cellular functions and blockage or progression of the tumor. In this review, we focus on PI3K/AKT signaling pathway and other related apoptotic processes contributing to glioblastoma and investigate the role of micro RNAs interfering in apoptosis, invasion and proliferation of glioma through such apoptotic processes pathways. Databases NCBI, PubMed, and Web of Science were searched for published English articles using keywords such as 'miRNA OR microRNA', 'Glioblastoma', 'apoptotic pathways', 'PI3K and AKT', 'Caspase signaling Pathway' and 'Notch pathway'. Most articles were published from 7 May 2015 to 16 June 2020. This study focused on PI3K/AKT signaling pathway affecting glioma cells in separated subparts. Also, other related apoptotic pathways as the Caspase cycle and Notch have been also investigated. Nearly 40 miRNAs were found as tumor suppressors or onco-miRNA, and their targets, which regulated subcomponents participating in proliferation, invasion, and apoptosis of the tumoral cells. Our review reveals that miRNAs affect key molecules in signaling apoptotic pathways, partly PI3K/AKT, making them potential therapeutic targets to overcome the tumor. However, their utility as a novel treatment for glioblastoma requires further examination and investigation.
# Roshanak Ghaffarian Zirak and Hurie Tajik are equally the first authors.
Hossein Javid; Isaac Hashemy; Soudabeh Shahid sales; Nema Mohammadian Roshan; Tayyebeh Kianoosh; Farnaz Zahedi Avval
Abstract
Background & objective: Globally, breast cancer is the most common malignancy among females. Prohibition (PHB)-I, a homologous protein, was initially introduced as a suppressor gene for amplification process. Further, the protein has a key role in the cell cycle and is capable of inhibiting ...
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Background & objective: Globally, breast cancer is the most common malignancy among females. Prohibition (PHB)-I, a homologous protein, was initially introduced as a suppressor gene for amplification process. Further, the protein has a key role in the cell cycle and is capable of inhibiting DNA transcription in many cell types. Therefore, its possible role in different types of human malignancies is of interest. The current study aimed at examining the relationship between the tissue distribution of PHB-I and prognostic factors of breast cancer. Method: Paraffin-embedded tissue specimens of 33 patients diagnosed with breast cancer at Omid teaching Hospital, Mashhad, Iran were studied and a commercial monoclonal antibody was used to perform immunohistochemistry (IHC). The relationship between PHB-I tissue expression with age, disease stage, tumor grade and size, as well as hormone receptor status including estrogen (ER) and progesterone (PR) receptors, and Her-2 receptor were evaluated. Results: The Immunohistochemical analysis showed a relative increase in PHB-I tissue expression along with higher tumor grade (P=0.057). In addition, higher expression of ER and PR were observed (P=0.027 and 0.009, respectively). The age of patients and other prognostic factors including Her-2 receptor status and disease stage did not statistically correlate with PHB-I expression. Conclusion: An increased expression of PHB-I was observed in the breast cancer tumors of the current study patients compared with the anatomically healthy margin. Its coloration with some prognostic factors such as disease grade and expression of ER and PR might indicate the PHB-I potential application for diagnostic and patient management purposes.
