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Order Nodamuvirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The MrNV VLPs remarkably contributed to the viral nanotechnology as a novel promising platform to display foreign epitopes. First, a putative hepatitis B vaccine was constructed. Thus, Yong et al. (2015a) displayed the determinant “a” located at aa 121–149 of surface protein (HBs) of hepatitis B virus (see Chapter 37). The MrNV coat of 1–377 aa residues was provided C-terminally with the HBs “a” determinant of 49 aa residues corresponding to the HBs 111–159 aa stretch, myc epitope EQKLISEEDL and His6 tag. The total length of the C-terminal addition reached 79 aa residues. The chimeric gene was expressed in E. coli and ensured generation of the appropriate VLPs. The immunization of mice with the purified chimeric VLPs induced specific antibodies against the HBs determinant “a” as well as more natural killer and cytotoxic T cells, which are vital for virus clearance (Yong et al. 2015a).
Advances in Genome Editing
Published in Yashwant Pathak, Gene Delivery, 2022
The use of chimeric gene editing tools to target gene adjustment is a potent way of assessing gene function and thereby manipulating cellular behaviour and functioning. Thanks to these genome editing techniques, the investigators have been able to employ genetically altered animals to better understand the epidemiology of many diseases and to elucidate underlying pathways that can be explored for better therapeutic approaches. The execution for disease treatment can be done in two ways: first, cells can be withdrawn from a patient or donor and edited outside the body before being reintroduced into the patient, or the genome editor can be introduced directly into the in vivo, using nano delivery systems (Li et al., 2020a; Mills et al., 2020). It’s vital to note that gene editing’s therapeutic effectiveness is dependent on the number of parameters, including editing efficacy, which varies greatly relying on the type of cell, ageing condition, and cell cycle stage of the recipient (Rodríguez-Rodríguez et al., 2019). Other variables that impact therapeutic efficacy include cell proficiency, which alludes to the viability of achieving a therapeutic reconfiguration baseline, and the effective transmission of programmable nuclease structure to the target tissue. Along with these factors, precision of the editing process is considered the important facet of the technique (Wang et al., 2017). In cell lines, disease models, and humans, genome editing procedures have been used to treat a variety of genetic ailments (Table 2.1).
Soft Tissue Sarcomas
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Thomas F. DeLaney, David C. Harmon, Karol Sikora, Francis J. Hornicek
Most synovial cell sarcomas are characterized by the translocation t(x;18)(p11.2;q11.2). The breakpoint of this translocation fuses the SYT gene (also known as the SS18 gene) from chromosome 18 to one of two homologous genes, SSX1 or SSX2, on the X chromosome. The SYT–SSX gene has recently been shown to increase the transcription of genes, such as Sox2 that is necessary for synovial cell sarcoma proliferation. The nature of the chimeric gene may have prognostic and pathogenetic importance. In some studies, metastasis-free survival was higher with SYT–SSX2 compared to SYT–SSX1. SYT–SSX1 is associated with biphasic tumors (glandular epithelial differentiation on a background of spindle tumor cells), whereas SYT–SSX2 is associated with monophasic tumors that lack glandular epithelial differentiation, although other studies have questioned these findings.
Pharmaceutical strategies in improving anti-tumour efficacy and safety of intraperitoneal therapy for peritoneal metastasis
Published in Expert Opinion on Drug Delivery, 2021
Puxiu Wang, Xiujuan Qu, Xiaofang Che, Qiuhua Luo, Xing Tang, Yunpeng Liu
Combinatorial therapy with multiple genes by different mechanisms could provide desirable efficacy and safety due to their synergistic effects. Cholesterol-modified polymeric nanoparticles (PCX), containing a triple therapeutic gene, were developed as vectors with high tumor accumulation, low systemic toxicity, and improved anti-tumor efficacy for the IP treatment of metastatic pancreatic cancer [101]. Moreover, chimeric gene fusion has been developed to provide synergistic effects or overcome some disadvantages of the single gene in tumor therapy. p53-Bad, designed by combining p53 with the mitochondrial pro-apoptotic factor Bad, could target the key driver p53 mutation and facilitate mitochondrial priming to overcome drug resistance in ovarian cancer cells.
The place of trabectedin in the treatment of soft tissue sarcoma: an umbrella review of the level one evidence
Published in Expert Opinion on Orphan Drugs, 2019
Pavlina Andreeva-Gateva, Shenol Chakar
For some patients, especially those with certain subtypes of STS that respond favorably to trabectedin therapy, such as leiomyosarcomas, myxoid liposarcomas, and synovial sarcomas, the duration of disease control exceeds that of other types of therapies. The drug mainly showed activity in myxoid liposarcoma with a FUS-CHOP or DDIT3-CHOP translocation. (12;16)(q13;p11), which creates the FUS-DDIT3 chimeric gene, which transcriptional product acts as an abnormal transcription factor [63].
Cytogenetic and molecular genetic methods for chromosomal translocations detection with reference to the KMT2A/MLL gene
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Nikolai Lomov, Elena Zerkalenkova, Svetlana Lebedeva, Vladimir Viushkov, Mikhail A. Rubtsov
PCR methods are the fastest and least expensive, and therefore most commonly used for the detection of chromosomal rearrangements. In addition, they are very sensitive—due to amplification, it is possible to detect a small number of copies of the chimeric gene/transcript in a large amount of normal DNA/RNA. Therefore, they can be used for MRD monitoring.