Principles of oncology
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
If it is accepted that a cancer starts from a single transformed cell then it is possible, using straightforward arithmetic, to describe the progression from a single cell to a mass of cells large enough to kill the host. The division of a cell produces two daughter cells. The relationship 2n will describe the number of cells produced after n generations of division. There are between 1013 and 1014 cells in a typical human being. A tumour 10 mm in diameter will contain about 109 cells. Since 230 = 109 this implies that it would take 30 generations to reach the threshold of clinical detectability and, as 245 = 3 × 1013, it will take fewer than 15 subsequent generations to produce a tumour that, through sheer bulk alone, would be fatal. This is an oversimplification because cell loss is a feature of many tumours, and for squamous cancers as many as 99% of the cells produced may be lost, mainly by exfoliation. It will, in the presence of cell loss, take many cellular divisions to produce a clinically evident tumour – abundant opportunity for further mutations to occur during the preclinical phase of tumour growth. The growth of a typical human tumour can be described by an exponential relationship, the doubling time of which increases exponentially – so-called Gompertzian growth (Figure10.2). This Gompertzian pattern has several important implications for the diagnosis and treatment of cancer.
Introduction
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
Countless modifications occur in the information stored in the genome — some are programmed, which is obvious from the cyclical evolution of the functions of the organism through its life span, others are stochastic. Stochastic modifications of the information stored are partly due to the reorganization taking place in the nuclear and mitochondrial DNA. As described in this volume, one of the sources of this reorganization is the inevitable modifications that occur in the genome through the division cycle, within proliferative cell compartments. It has become apparent that after each division, a daughter cell is not exactly identical to the mother cell and its sister cell. Quantitative and qualitative changes create a drift that progressively becomes expressed in cell functioning. Cell division is a necessary renewal mechanism, but has its price. It creates a drift in a cell compartment that modifies its function and its subsequent interactions with other compartments.
Repair of Radiation Damage
Kedar N. Prasad in Handbook of RADIOBIOLOGY, 2020
Chinese hamster cells can repair potentially lethal radiation damage if incubated in Earle’s balanced salt solution immediately after a single exposure.5 Not only the parent cells, but the daughter cells as well, retain the capacity to repair potentially lethal damage.47 This is demonstrated in the following experiment. Lung cells of the female Chinese hamster (V79-4) were X-irradiated (800 R) and incubated at 37°C. When the average number of cells per colony (N) of irradiated cells was two to three — usually within 20–24 hr after irradiation — the medium was removed, cells were rinsed with Puck’s saline F(PSF), and the rinse solution was discarded and replaced with a fresh buffer. After incubation in the buffer for various intervals of time, the buffer was removed and a fresh growth medium was added for colony formation.
Potential applications of mesenchymal stem cells and their derived exosomes in regenerative medicine
Published in Expert Opinion on Biological Therapy, 2023
Maryam Adelipour, David M. Lubman, Jeongkwon Kim
Stem cells are known to have the abilities of proliferation and the generation of identical daughter cells, as well as the capability of differentiation into other types of cells. According to their sources, there are four types of stem cells: embryonic stem cells, placental and umbilical cord stem cells, adult stem cells, and induced pluripotent stem cells (iPSCs) [5,6]. Even without considering the moral and ethical implications, human embryos are not the ideal source from a technical perspective. Other sources of stem cells, such as the placenta, umbilical cord, and many adult tissues, possess MSCs, which are multipotent cells that can differentiate into several types of cells [4,7,8]. Especially, extracellular vesicles (EVs), mainly exosomes, secreted by MSCs have emerged as a promising therapeutic strategy to treat a variety of diseases [9,10]. In this study, we conducted a literature search using databases such as Google Scholar and PubMed to identify relevant articles on the therapeutic applications of mesenchymal stem cells (MSCs) and their exosomes in the context of degenerative medicine. The search was performed with the following keywords: ‘MSC,’ ‘exosome and MSC,’ ‘degenerative medicine,’ ‘encapsulation,’ ‘preconditioning,’ ‘gene modification,’ ‘bioprinting,’ and ‘clinical trials.’ We searched for articles published between 2017 and 2022. The aim of this review is to provide an overview of the applications of MSCs and their secreted exosomes in regenerative medicine.
Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2
Published in Journal of Receptors and Signal Transduction, 2021
Bishajit Sarkar, Md. Asad Ullah, Syed Sajidul Islam, MD. Hasanur Rahman, Yusha Araf
Due to the supercoiled structure of the DNA molecules, it is necessary to unwind the double-stranded DNA before replication, transcription, recombination, and other processes. DNA topoisomerases are the enzymes that function in unwinding, cutting, shuffling, and relegating the DNA double helix structure. The human genome encodes six topoisomerases that are grouped into three types: type Iα, type Iβ, and type IIα. DNA topoisomerase IIα is one of the necessary topoisomerases that function in various cellular functions. However, it is a genotoxic enzyme which can lead to cancer development. When DNA topoisomerase II cuts the double-stranded DNA, it may remain covalently attached to the broken end of the DNA. This reaction intermediate is known also as the cleavage complex. If the amount of the cleavage complex in the cell falls too much, then the cells are not able to divide into daughter cells due to mitotic failure, which results in the death of the cells. Moreover, if the amount of the cleavage complex increases too much, the temporary cleavage complex structures can become permanent double-stranded breaks in the DNA. These double-stranded breaks are caused by the faulty DNA tracking system which then initiates the faulty recombination and repair pathways of DNA replication and expression, leading to cancer (Figure 2). For this reason, DNA topoisomerase IIα is a potential target for anti-cancer drug development [77–81].
Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials
Published in Expert Opinion on Investigational Drugs, 2019
Stephen A. Goutman, Masha G. Savelieff, Stacey A. Sakowski, Eva L. Feldman
Stem cells were originally proposed as an ALS treatment to replenish the populations of progressively lost MNs. Stem cells possess the ability to self-renew and maintain an undifferentiated state. When they divide, the parent cell retains stemness while the daughter cell can differentiate [9]. Embryonic stem cells (ESCs) are totipotent and can differentiate into any cell type, while pluripotent stem cells (PSCs) can differentiate into more limited, specific cell types [9]. Neural progenitor cells (NPCs) are PSCs that can differentiate into neuronal or glial cells [9,10]. The original notion for ALS stem cell therapy was to employ ESCs or PSCs to generate MNs for transplantation into ALS patients. Unfortunately, in practice, the concept proved harder to implement [11–13]. In order to integrate seamlessly with preexisting neural circuits, transplanted stem cell-derived MNs need to project axons, frequently over significant distances, and synapse with endogenous neurons and muscle, all the while enduring a diseased microenvironment [11,13].
Related Knowledge Centers
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