Zabel Physical Aspects of Therapeutics

2. completely revised Auflage 2023
ISBN: 978-3-11-116906-4
Verlag: De Gruyter
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 3, 309 Seiten

Reihe: Medical Physics

The updated edition of the third of three vollumes on Medical Physics presents modern physical methods for medical therapy with a focus on tumor treatment. It provides background information on radiation biology, radiation response of tissues, and linear energy transfer through radiation. Therapies with external radiation sources (x-rays, protons, neutrons) as well as internal radiation sources (brachytherapy) are discussed in detail. Other chapters deal with the use of lasers and nanoparticles in modern medicine. This volume closes with a short chapter on medical statistics. NEW: highlighted boxes emphasize specifi c topics; math boxes explain more advanced mathematical issues; each chapter concludes with a summary of the key concepts, questions, exercises, and a self-assessment of the acquired competence. The appendix provides answers to questions and solutions to exercises.

Zielgruppe

R&D laboratories in bio-medical engineering, researchers and stud

Autoren/Hrsg.

Zabel, Hartmut

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizin, Gesundheitswesen Medizintechnik, Biomedizintechnik, Medizinische Werkstoffe
• Technische Wissenschaften Sonstige Technologien | Angewandte Technik Medizintechnik, Biomedizintechnik
• Naturwissenschaften Physik Angewandte Physik Medizinische Physik

Leseproben

Part D: Radiotherapeutical methods
1 Radiobiology basics
Important parameters Number of chromosome pairs 23 Number of DNA bases 4 Telomere length ~50 Most effective LET 100 keV/µm (100 eV/nm) LET of 10 MeV protons 4.7 keV/µm Dose of single fraction 8–10 Gy Total dose for cancer treatment ~60 Gy RBE of x-rays 1 RBE of protons 2–3 1.1 Introduction
The aim of this chapter is to provide a basic understanding of the cell’s life cycle and the difference between normal and cancerous cells. This information is instrumental for preparing a radiation treatment plan to fight the proliferation of cancer cells with photons, charged particles, or neutrons, as discussed in Chapters 2–5. In addition, we discuss here the relationship between radiation dose and cell survival rate, which is pivotal for the following chapters on radiation therapy. More details on the cell cycle can be found in standard biology [1] or physiology textbooks listed under “Further reading.” Genes and a number of messenger proteins determine when and how quickly cells grow, when they divide (mitosis) and when they die (apoptosis). Some cells only live very briefly, such as the cells in the epithelial layer of the intestine (1.5 days). Other cells have a fairly long life span, such as the skin epidermis cells (20 days) or the red blood cells (up to 60 days). Some cells live long like osteocytes (25–30 years), and some cells never die like nerve cells. The cells that die over time need to be replaced. Those who never die cannot be recovered even if injured, which is the problem with spinal cord injuries. For unknown and uncontrolled reasons, a normal cell can suddenly turn into a dysfunctional cell that overrides all life cycle rules and death of a “normal” cell. Then the cell becomes cancerous. Radiation therapy is currently one of three methods of fighting cancer cells; the other two methods are chemotherapy and surgery. These procedures can also be referred to as “burning,” “poisoning,” and “cutting.” Although radiation treatment of tumor cells has seen tremendous development and refinement in recent years, it may not be the ultimate solution to fighting this disease. At the same time, enormous progress has been made in understanding the cell “machinery” so that biochemical cancer therapy through targeted drugs or immunizations is foreseeable in the near future. The Nobel Prize in Medicine 2018 was awarded to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibiting negative immune regulation” [2]. Immune therapy of cancer is a novel and promising direction. But for the meantime, radiation treatment of cancer remains the second-best solution. 1.2 Life cycle of cells
The normal life cycle of cells can be subdivided into two main phases: interphase and mitotic phase (M); see Fig. 1.1.1 The interphase and mitotic phase constitute one cell cycle. During the interphase, normal cell activity occurs, including growth and DNA replication. The interphase occupies 90% of a cell cycle. The remaining 10% go to the mitotic phase, where the cell divides itself into two identical copies. After cell division is completed, both cells have the exact same genetic information, and the interphase starts over again, simultaneously in both new cells. Fig. 1.1: Life cycle of a cell. G1,?growth phase; G0,??rest phase; CP1, first check point in G1 phase; S,?replication phase; G2,?second growth phase; CP2, second check point in G2 phase; M,?mitosis. The mitosis or cell division phase is subdivided into four subphases: prophase, metaphase, anaphase, and telophase. Red flags indicate checkpoints. At the end of the telophase, two identical new daughter cells are formed. The life cycle of cells begins with the growth phase G1, in which the cell enlarges and synthesizes new proteins. Toward the end of this phase, a checkpoint (CP1) controls stop or go to the next phase. In case of stop, the cell goes into a rest phase G0. It remains there until called upon, for instance, for repairing injuries. Most body cells are in the rest phase G0 and fulfill their specified duties. The cell will complete the cycle and divide if the checkpoint gives a green light. For cell regulation, the checkpoint is essential. If the stop signal is overwritten in any way, uncontrolled replication of the cell can result, as we will see later. The total genetic information is contained in any cell and is encoded in double-stranded DNA molecules. The genetic information of humans, the genome, is written in 46 chromosomes, each one containing one long DNA molecule. These 46 chromosomes come in 23 homologous pairs; one of each pair is inherited from the mother and father. Both chromosomes in a pair contain essentially the same genetic information governing the basic function of organs. This is true for the first 22 chromosomes. However, the 23rd pair is different for female (XX) and male (XY), determining the sex. Three pairs of chromosomes in their G1-phase are sketched in Fig. 1.2(a), representative of all others. During the S-phase, cells replicate their genetic material, ensuring that each daughter cell will receive an exact copy during the mitotic phase. The two strands are copied in opposite directions (leading and lagging strands) during DNA replication using different transcription methods (for more information see Infobox I). After replication is completed, the DNA condenses into chromosomes. The chromosomes are a heavily coiled and folded-up version of long DNA strands. Only in this condensed phase can chromosomes be recognized by an optical microscope. Otherwise, the thin DNA chains do not offer sufficient contrast to be recognized. Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), which separate during cell division. The sister chromatids are attached to each other by a centromere; see Fig. 1.2(b). The centromere is a narrow “waist” of the duplicated chromosome, where two chromatids are most closely attached. Centromeres are important for organizing the associated chromatids in the cell and for their mechanical separation in the mitotic phase. Once separated by cell division, the chromatids are called chromosomes. Fig. 1.2: Cell division starting from the G1-phase to the end of the M-phase. (a) In the G1-phase, all 46 chromosomes appear in homologous pairs; only three representative ones are sketched. (b) In the S-phase DNA replication and synthesis takes place, which condenses to sister chromatids in the prophase at the beginning of the M-phase. (c) In the anaphase, the sister chromatids are pulled apart to opposite halves of the cell. (d) In the final telophase, complete separation and generation of two new identical cells occur. Most cells replicate with different rates during the human life span. Each cell contains the complete genetic code stored in 46 chromosomes. During replication, exact copies of all chromosomes are generated. Subsequently, the original cells are divided into two, each one containing one identical copy. Infobox I: DNA replication Figure source: https://en.wikipedia.org/wiki/Base_pair; https://de.wikipedia.org/wiki/Chromosom; https://en.wikipedia.org/wiki/DNA_replication Deoxyribonucleic acid (DNA) is the main molecule in cells responsible for storing and reading genetic information that supports all life, both bacterial and human. DNA is a linear polymer consisting of two strands arranged in a double helix (panel c). These strands are made up of subunits called nucleotides (panel (a)). Each nucleotide contains a phosphate, a five-carbon sugar molecule, and a nitrogenous base. The bases in DNA are adenine (“A”), thymine (“T”), guanine (“G”), and cytosine (“C”). They are always arranged in pairs: adenine pairs with...

Über Autor(innen)

Hartmut Zabel received his doctorate in 1978 from the LM University of Munich in the field of physics on a topic in condensed matter physics. He then spent a year as a postdoctoral fellow at the University of Houston, Texas, and joined the faculty of the University of Illinois at Urbana-Champaign in 1979 as Assistant Professor, where he was promoted to Associate Professor in 1983 and Full Professor of Physics in 1986. In 1989 he received a call to the Ruhr University Bochum and held the chair for experimental physics/condensed matter physics from 1989 to 2012. He maintained his connection to the University of Illinois as Adjunct Professor of Physics. After his retirement in 2012, he was first a Senior Professor at the Ruhr University and from 2014 to 2018 Distinguished Guest Professor at the Johann Gutenberg University in Mainz. In addition, he was a guest researcher at various universities and institutions, i.a. at Brookhaven National Laboratory (USA), Risø National Laboratory (Denmark), University of Kyoto, National Institute of Science and Technology, Gaithersburg-Washington, KTH Stockholm, and Uppsala University (Sweden). He was also member and chairperson of various scientific committees and advisory bodies, including those at the Paul Scherrer Institute in Switzerland, the Institut Laue-Langevin (Grenoble, France), Argonne National Laboratory, and the Helmholtz Center Berlin. In 1996 he was elected a Fellow of the American Physical Society, in 2001 he received an honorary doctorate from the KTH in Stockholm, In addition to his scientific work at the University of Illinois and the Ruhr University Bochum with over 500 publications in peer-reviewed scientific journals on the structure, dynamics, magnetism and superconductivity of solids, he was supervisor and co-supervisor of more than 50 doctoral students in Urbana, Bochum and Mainz, organizer and co -organizer of numerous international workshops and conferences, editor and co-editor of five books, and guest lecturer at many summer schools in Europe. i.a. he was a guest lecturer in the European Graduate School "HERCULES" in Grenoble for the last 30 years, lecturing on the topic of scattering experiments with synchrotron radiation and neutrons. At the beginning of 2000, the medical department at the Ruhr University Bochum developed a new study concept based on the model of the University Hospital Charité in Berlin: problem-oriented learning (POL). As a representative of the physics department, Hartmut Zabel was involved in the curriculum development. In addition to the standard physics course for medical students, he also supervised the physics-related seminars in the POL teaching format. Finally, he developed a new lecture series on "Medical Physics" for physics students and initiated a master course "Medical Physics" at the Ruhr University Bochum, which was later established and certified.