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.
GI, Liver & Pancreas Pathology
Dina Mohamed Allam; Hend Ahmed Kasem; Amira Hegazy; Shereen Fathy Mahmoud
Abstract
Background & Objective: Colorectal carcinoma (CRC) is the third leading cause of cancer-caused death worldwide and constitutes about 6.48% of all malignancies in Egypt. Studying the molecular profile of CRC is essential for developing targeted therapies. STAT3 and CTLA4 expression are among the molecular ...
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Background & Objective: Colorectal carcinoma (CRC) is the third leading cause of cancer-caused death worldwide and constitutes about 6.48% of all malignancies in Egypt. Studying the molecular profile of CRC is essential for developing targeted therapies. STAT3 and CTLA4 expression are among the molecular abnormalities claimed to cause CRC progression and chemo-resistance. Therefore, they could be used as potential therapeutic targets. This study aimed to evaluate pSTAT3 and CTLA4 expression levels and their possible roles as prognostic and predictive biomarkers in CRC using immunohistochemistry (IHC).Methods: This retrospective study included 113 CRC patients. Tissue microarrays were constructed, followed by pSTAT3 and CTLA4 antibodies immunostaining. Their expression was assessed and compared with clinicopathological parameters and survival data.Results: Both pSTAT3 and CTLA4 overexpression were significantly associated with poor prognostic parameters, such as the presence of distant metastasis (P=0.02 & 0.03), high grade (P<0.001 & 0.03), high mitotic count (P<0.001 & 0.03), high tumor budding group (P=0.008 & 0.04), infiltrating tumor border (P<0.001 & 0.007) respectively, and advanced pathological stage with pSTAT3 (P=0.02). A significant association was found between overexpression of both markers and short overall survival. Correlations between the H-score of pSTAT3 and CTLA4 in CRC showed a significant positive correlation (P<0.001).Conclusion: STAT3 and CTLA4 positivity have been linked to the development and progression of CRC, and they may provide potential prognostic indicators and therapeutic targets for CRC patients.
Diagnostic Pathology
Soheil Vazifedust; Hadi Esmaeili Gouvarchin Ghaleh; Mostafa Khafaei; Fateme Azemati; Bahman Jalali Kondori
Abstract
Background & Objective: Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies ...
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Background & Objective: Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies for MS, the disease progresses and relapses through several immunological pathways. New medicines aimed at remyelination and neurodegeneration are being developed; however, they need stronger evidence before being introduced into routine clinical care. The purpose of this study was a thorough assessment of MS immunopathology and predictive biomarkers.
Methods: Immunotherapy, immunopathogenesis, and prognostic biomarkers were all parts of the search method. Only publications in English were considered for inclusion in the study. For that purpose, we went through the current state of knowledge around MS immunopathology and related biomarkers. Immunology, as well as the identification of increased inflammation as an important component of neurodegeneration, shaped our understanding of this disease aetiology. The relevant sources examined covered the years 2015-2021.
Conclusion: We found biomarkers in the cerebrospinal fluid and blood that might be used for the prediction and diagnosis of MS, as well as for measuring treatment response and adverse effects. Many variables, including the role of some infectious organisms and the impact of environmental and social factors, might contribute to the immunological dysfunctions seen in MS. Patients with MS may benefit from better therapy options if a better understanding of MS biomarkers and immune response mechanisms would be obtained.
