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The Immunological System and Neoplasia
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
In the previous section, the basic concepts regarding tumor cell development were discussed. In this section, the importance of the immune system for the elimination of these cells will be discussed. The notion that the immune system is able to recognize and destroy continuously arising tumor cells was first proposed by Ehrlich and later eloquently formulated by Burnet (1970) as follows: “The ′ thymus-dependent′ immune system arose from the evolutionary need to counter the development of malignant disease. Wandering cells ancestral to lymphocytes developed the capacity to recognize anomaly (′not-self) on another cell surface and to react destructively on such recognition. “ As soon as this immunosurveillance hypothesis was formulated, it was questioned by several investigators because many observations failed to support this hypothesis. For example, nude or athymic mice and rats, as well as mice and rats thymec-tomized at birth, do not have an increased susceptibility to chemically induced or “spontaneous” tumors, although they tend to develop tumors of the lymphoreticular system more frequently than intact mice.
The Molecular Basis of Bladder Cancer and Prospects for Gene Therapy Using Hammerhead Ribozymes
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Eric J. Small, Mohammed Kashani-Sabet, David Y. Bouffard, Kevin J. Scanlon
Cancer results from an accumulation of genetic injuries to biochemical pathways that regulate cell proliferation. Two key gene sets, the proto-oncogenes and the tumor suppressor genes, play vital balancing roles in guiding normal cell development and growth. Damage to tumor suppressor genes allows uncontrolled growth of cancer cells. The human retinoblastoma (Rb) gene is the prototype, as well as one of the best characterized, of the tumor suppressor genes (Goodrich and Lee, 1993). The human p53 gene is also a tumor suppressor gene which has been extensively described (Levine et at, 1991). Both p53 and Rb appear to play important roles in the biology of transitional cell carcinoma of the uroepithelieum. The H-ras oncogene is an example of a proto-oncogene contributing to the malignant phenotype of transitional cell carcinoma following an activating mutation.
T Cells:Regulation and Cellular Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Developing T cells express receptors for several cytokines which affect proliferation and differentiation (Table 6–III). The thymic hormones described above also play a role. Cytokines are secreted by epithelial cells, macrophages, and other cells. T cells themselves may produce several cytokines during development, and these may modulate the activity of the developing T cells as well as the thymic cells which are “controlling” the process (Table 6–IV). That is, T cell development may be influenced by factors produced by the developing cells themselves. IL-7 may be the cytokine which influences the earliest stages of thymic T cell development. TCR−CD3−CD4−CD8− thymocytes proliferate in response to IL-7. The developmental stages at which other cytokines have effect, and their relationship to the intercellular contacts occurring during T cell differentiation have not yet been well-established.
Overview of gene expression techniques with an emphasis on vitamin D related studies
Published in Current Medical Research and Opinion, 2023
Jeffrey Justin Margret, Sushil K. Jain
During cell development, certain sets of genes express proteins that allow them to communicate with neighboring cells to coordinate development in multicellular organisms. All living organisms make use of this process, known as gene expression, to create the building blocks of life from genetic information1. The exceedingly complex process of gene expression enables cells to control their size, shape, and functions as it involves the interactions among DNA, RNA, and proteins, as well as with the environment. The phenotype of an organism is determined by how its genes are expressed2 and regulated at many levels. The protein expressed determines the function of the cell, and each cell type has a unique gene expression profile. Thus, gene expression profiling is a fundamental tool with which to investigate changes in the expression at a cellular level, thus unraveling the complexity of biological systems and the effects of mutations that result in disease states or pathobiology.
Current updates and future perspectives in the evaluation of azoospermia: A systematic review
Published in Arab Journal of Urology, 2021
Nahid Punjani, Caroline Kang, Dolores J. Lamb, Peter N. Schlegel
Many of the men identified as having single gene defects that are causally linked with severe defects in spermatogenesis present with a histological picture of maturation arrest [24]. In this condition, early germ cells are typically present in normal numbers, but development of these germ cells stops (often uniformly) at a specific developmental stage resulting in azoospermia. In many cases, expression of the defective gene occurs at or near the developmental stage where spermatogenesis is disrupted. These observations not only suggest that germ cell development was caused by the genetic variant, but also raise the potential to treat the maturation arrest condition by replacing the gene or gene product or supporting sperm development using a specific intervention based on the identified genetic defect. In this treatment approach, identification of the specific causal defect for infertility would be a critical first step in developing a personalised approach to treatment of these patients who present with vexing clinical cases that currently have a limited prognosis for sperm retrieval.
Decreased peripheral blood memory B cells are associated with the presence of interstitial lung disease in rheumatoid arthritis: a case-control study
Published in Modern Rheumatology, 2021
Toshiaki Shimizu, Yasuo Nagafuchi, Hiroaki Harada, Yumi Tsuchida, Haruka Tsuchiya, Norio Hanata, Shoko Tateishi, Hiroko Kanda, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Intensive treatment with immunosuppressive agents, including cyclophosphamide, improves the prognosis of patients with acute exacerbations of RA-ILD [20], and cyclophosphamide treatment significantly reduces the B cell count in CTD, including RA [21]. Efficacy of both rituximab and abatacept has been shown in ILD-associated RA [22]. Therefore, we also analyzed the T cell subsets of peripheral blood in RA patients with and without ILD. However, we did not observe any statistically significant differences in the frequencies of T cell subsets (data not shown). These results suggest that B cells play a more direct role in ILD-associated RA than do T cells. How memory B cells contribute to ILD is unknown. As mentioned above, some authors have suggested possible roles of local B cells in ILD-associated RA, which might occur due to the migration of SwMB from the peripheral blood to lung tissues in ILD patients. In our study, RA-ILD patients tended to have higher total B cell count. On the other hand, there was a reduction in the frequency of memory B cells in RA-ILD patients. These results suggest that there may be a mechanism that increases B cells in RA-ILD patients and that some of them selectively migrate to the lung tissues. Alternatively, our results may suggest that the decrease in certain B-cell subsets induce upreguration of B cell development to compensate for it. In such situations, analysis of bronchoalveolar lavage fluid or lung tissue may be useful.