China
Africa
Explore chapters and articles related to this topic
MicroRNAs in Human Cancers and Therapeutic Applications
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Ji Young Yoo, Balveen Kaur, Tae Jin Lee, Peixuan Guo
Locked nucleic acid (LNA) is a RNA analog generated by chemically locking the 2′-oxygen and 4′-carbon on ribose with a bridge. The locked structure physically inhibits binding of RNase, resulting in high stability in serum but still leaves the LNA capable of pairing with complementary RNA stands. As a result, LNAs are frequently used to bind complementarily to functional miRNAs for use in fluorescence staining or targeted inhibition (Wahlestedt et al., 2000). While unmodified oligonucleotides can be degraded within 1.5 hours in serum, the half-life of LNA in serum can reach up to 15 hours (Kurreck et al., 2002). LNA-based anti-miR-155 drug (MRG106) administered through intratumoral injection was developed by MiRagen Therapeutics, which is currently undergoing Phase 1 clinical trial for patients with cutaneous T-cell lymphoma (CTCL) of the mycosis fungoides (MF) sub-type (NCT02580552).
Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
HDACi are being actively pursued for the treatment of cancers. HDACi Vorinostat and Romidepsin are approved for treatment of cutaneous T cell lymphoma. HDACi has been shown to modulate tumor metabolism by virtue of its effect on gene expression. HDACi treatment was associated with a significant reduction in glucose uptake and glycolysis in breast, colon, lung and multiple myeloma cancer cell lines (Alcarraz-Vizan et al., 2010; Wardell et al., 2009; Amoedo et al., 2011; Rodrigues et al., 2015). Such alterations are driven by decreased expression glucose uptake transporters and key glycolytic enzymes (Wardell et al., 2009), and increase reliance on mitochondrial metabolism (Amoedo et al., 2011). These studies imply that HDACi might selectively target cancer cells with Warburg’s phenotype.
Role of Engineered Proteins as Therapeutic Formulations
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Khushboo Gulati, Krishna Mohan Poluri
Bai et al. engineered a complex G-CSF-Tf containing the granulocyte colony-stimulating factor (G-CSF) in fusion with transferrin (Tf). Subcutaneous administration of this complex in mice resulted in an effective increase in absolute neutrophil counts as compared to the condition when the G-CSF was administered alone. The complex also resulted in myelopoietic effect that lastest for three days. This implies that fusion of recombinant proteins with transferrin is a promising technique for the future protein drugs (Bai et al., 2005). The researchers further improved the oral efficacy of the fusion protein by adding the linker peptide (helix linker H4-2) between the G-CSF and Tf domains. Addition of such a linker significantly improved their in vivo myelopoietic effect (Bai and Shen, 2006). A fusion conjugate of IL-2 and EDT (enzymatically active domain of diphtheria toxin) was approved as an engineered protein therapeutic as it is successful in treating cutaneous-T-cell lymphoma (Foss, 2006).
A comprehensive summary of disease variants implicated in metal allergy
Published in Journal of Toxicology and Environmental Health, Part B, 2022
In addition to the many variants of ASIA that were correlated with metal hypersensitivity, allergic reactivity to sensitizing metals was also suggested to play a role in the promotion of a certain type of cancer – cutaneous T-cell lymphoma (CTCL). Many subtypes of CTCL were identified, but all variants of the disease are classified as extranodal non-Hodgkin’s lymphomas, wherein malignant monoclonal T-lymphocytes selectively infiltrate the skin (Bagherani and Smoller 2016). In the early stages of disease development, CTCL is often misdiagnosed as one of many common inflammatory skin conditions including ACD, psoriasis, lichen planus, folliculitis, or vitiligo (Hristov, Tejasvi, and R 2021). Interestingly, many subjects that develop CTCL have a history of these and other similar skin disorders. It is believed that these conditions often represent a precursor to cancerous transformation due to recurrent antigenic stimulation associated with chronic disease states. Accordingly, several cases of CTCL were correlated with chronic ACD induced by Cr, Ni, and Co (Khamaysi et al. 2011; Tilakaratne and Sidhu 2015).