Chronic myeloid leukemia as a stem cell-derived malignancy

Chronic myeloid leukemia (CML) is a myeloproliferative disease of the hematopoietic stem cells, characterized by the presence of the Philadelphia (Ph) chromosome. Although imatinib inhibits the BCR-ABL kinase activity, clinical experiences confirm that imatinib may not target CML stem cells in vivo. The identification of signaling pathways responsible for the self-renewal properties of leukemic stem cells in CML will help in the discovery of novel therapeutic targets. Here we review signaling pathways including Wnt/β-catenin, Hedgehog, Alox5, and Foxo which play crucial roles in the maintenance of stem cell functions in CML. It is thought that inhibition of key genes that are part of self-renewal associated signaling pathways may provide an effective way to reduce aberrant stem cell renewal in CML

Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance

Two central questions in COVID-19 treatment which should be considered are: “How does the imbalance of the complement system affect the therapeutic approaches?” and “Do we consider complement inhibitors in therapeutic protocols?”. The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms “COVID-19”, “Complement”, “Complement inhibitor”, “SARS-CoV-2”, and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in “KEGG pathway database”. Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors

The expression of CD markers in solid tumors: Significance in metastasis and prognostic value

Objective. The clusters of differentiations (CDs) are among the surface markers expressed on different cells in the body, which are involved in the communication of cells with each other and the induction of signaling. Moreover, the evaluation of the ectopic expression of these markers in solid tumors has led to the detection of disease in early stages. In this paper, we have examined the effect of CD markers expression on the function of cancer cells, as well as their importance as the diagnostic and prognostic factors for monitoring the progression of solid tumors. Materials and methods Relevant literature was identified by a PubMed search (1988-2017) of English the language papers using the terms “CD markers”, “diagnostic”, “prognostic”, “predictive marker” and “solid tumors.” Discussion. Finally, it can be stated that the evaluation of CDs is not only of diagnostic value at disease onset, but these markers can be used as prognostic and predictive markers to contribute to the treatment of disease and predict its relapse. Conclusion. Monitoring of tumors progression through CDs expressed on circulating tumor cells could be a new diagnostic and prognostic factor in the future

Neoplastic Bone Marrow Niche: Hematopoietic and Mesenchymal Stem Cells

The neoplastic niche comprises complex interactions between multiple cell typesand molecules requiring cell-cell signaling as well as local secretion. These nichesare important for both the maintenance of cancer stem cells and the inductionof neoplastic cells survival and proliferation. Each niche contains a population oftumor stem cells supported by a closely associated vascular bed comprising mesenchyme-derived cells and extracellular matrix. Targeting cancer stem cells andneoplastic niche may provide new therapies to eradicate tumors. Much progresshas been very recently made in the understanding of the cellular and molecularinteractions in the microenvironment of neoplastic niches. This review articleprovides an overview of the neoplastic niches in the bone marrow. In addition tohighlighting recent advances in the field, we will also discuss components of theniche and their signaling pathways