Principles of chemotherapy

2018 ◽  
Author(s):  
Jim Cassidy ◽  
Donald Bissett ◽  
Roy A. J. Spence OBE ◽  
Miranda Payne ◽  
Gareth Morris-Stiff
Keyword(s):  
Biological Effects ◽  
Intraoperative Radiotherapy ◽  
Intensity Modulated Radiotherapy ◽  
Palliative Radiotherapy ◽  
Ionising Radiation ◽  
Whole Body ◽  
High Dose ◽  
X Rays ◽  
Image Guided Radiotherapy ◽  
Radical Treatment

Principles of radiation oncology outlines the physical and biological effects of ionising radiation, and its use in clinical oncology. Radiobiology, examining the response of tissue to ionising radiation, is described with regards to normal and malignant tissues. The effect of fractionation, the delivery of radiotherapy in a series of repeated exposures, is examined. The damaging effects on normal tissues are considered, particularly nonreversible late effects including carcinogenesis. Therapeutic exposure to ionising radiation is contrasted between radical and palliative radiotherapy. The physical properties of ionising radiation beams are described for superficial x-rays, megavoltage x-rays, and electrons. The process of treatment planning is summarised through beam dosimetry, target and critical organ outlining, dose planning, treatment verification, prescription and delivery. Computerised tomography is used for outlining and for verification, using cone beam CT. 0ther methods for image guided radiotherapy include fiducial markers. Increasingly intensity modulated radiotherapy is proving beneficial in reducing normal tissue damage during radical treatment. Stereotactic radiotherapy is used in the radical treatment of small unresectable malignancies. The clinical use of electron therapy, brachytherapy and intraoperative radiotherapy is described. Nuclear medicine uses unsealed radionuclides in imaging primary malignancies and their metastases, and in targeted radiotherapy. Examples include PET scanning, bone scanning, and radio iodine therapy. Whole body irradiation is used to improve outcomes after high-dose chemotherapy with stem cell or bone marrow transplantation.

Comparison of Biological Effects of Whole-Body Irradiation with 22.5-Mev X-Rays, 18-Mev Electrons, and 400-Kev X-Rays in the Rat

1955 ◽  
Vol 3 (4) ◽  
pp. 423 ◽  
Author(s):  
John B. Fuller ◽  
Irene Chen ◽  
John S. Laughlin ◽  
Roger A. Harvey
Keyword(s):  
Biological Effects ◽  
Whole Body ◽  
X Rays

scholarly journals The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200319 ◽  
Author(s):  
Dávid Kis ◽  
Eszter Persa ◽  
Tünde Szatmári ◽  
Lilla Antal ◽  
Attila Bóta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Extracellular Vesicles ◽  
Relative Proportion ◽  
Ionising Radiation ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
X Rays ◽  
Radiation Induced ◽  
Cell Subpopulations

Objectives: Ionising radiation-induced alterations affecting intercellular communication in the bone marrow (BM) contribute to the development of haematological pathologies. Extracellular vesicles (EVs), which are membrane-coated particles released by cells, have important roles in intercellular signalling in the BM. Our objective was to investigate the effects of ionising radiation on the phenotype of BM-derived EVs of total-body irradiated mice. Methods: CBA mice were irradiated with 0.1 Gy or 3 Gy X-rays. BM was isolated from the femur and tibia 24 h after irradiation. EVs were isolated from the BM supernatant. The phenotype of BM cells and EVs was analysed by flow cytometry. Results: The mean size of BM-derived EVs was below 300 nm and was not altered by ionising radiation. Their phenotype was very heterogeneous with EVs carrying either CD29 or CD44 integrins representing the major fraction. High-dose ionising radiation induced a strong rearrangement in the pool of BM-derived EVs which were markedly different from BM cell pool changes. The proportion of CD29 and CD44 integrin-harbouring EVs significantly decreased and the relative proportion of EVs with haematopoietic stem cell or lymphoid progenitor markers increased. Low-dose irradiation had limited effect on EV secretion. Conclusions: Ionising radiation induced selective changes in the secretion of EVs by the different BM cell subpopulations. Advances in knowledge: The novelty of the paper consists of performing a detailed phenotyping of BM-derived EVs after in vivo irradiation of mice.

Marked depression of radiation-induced emesis in frogs following prior exposure to a brief dose of X-rays

2002 ◽  
Vol 80 (8) ◽  
pp. 828-832 ◽  
Author(s):  
Yukihisa Miyachi ◽  
Takahisa Koike ◽  
Kenzo Muroi ◽  
Tomoko Kanao ◽  
Taro Kawamoto ◽  
...  
Keyword(s):  
Low Dose ◽  
Lethal Dose ◽  
Prior Exposure ◽  
Whole Body ◽  
High Dose ◽  
X Rays ◽  
Sham Control ◽  
Toxic Dose ◽  
Acute Emesis ◽  
Radiation Induced

Acute emesis response to harmful doses of X-rays on frogs (Rana porosa porosa) was examined. Results showed that the number of radioemesis events following exposure to 0.85 Gy was slightly higher than in the sham control animals. The increase in emesis action became more pronounced when the total dose of radiation was raised to 2.5 Gy. Only 1 frog out of a total of 12 did not show vomiting following radiation, while no response was observed in sham control animals. Note that animals in which the low dose rate of radiation was applied to whole body did not display any changes in the emesis response relative to control animals. The present studies, and those by others, showed that a brief dose of X-rays prior to a second exposure to a sub-lethal dose might induce a tolerance to radiation. An additional experiment was conducted to examine whether a small conditioning dose could induce a depression of radioemesis (tolerance) following an exposure to high dose X-ray. With prior exposure to 0.3 Gy, only 1 frog out of a total of 5 frogs vomited as a result of radiation exposure. Suppression of the emetic response became significant when the pre-radiation dose was decreased to 0.1 Gy. On the contrary, increasing the small conditioning dose to 0.5 Gy resulted in a remarkable rise of radiation-induced emesis. This results indicate that exposure to the smaller dose of X-rays elicits a tolerance effect to toxic dose level of radiation.Key words: emesis, hormesis, low-dose X-rays, resistance, frog.

Long-term effects of a single whole-body exposure of mice to ionizing radiations - II. Causes of death

1961 ◽  
Vol 154 (956) ◽  
pp. 350-368 ◽  
Keyword(s):  
Cause Of Death ◽  
Causes Of Death ◽  
Rate Of Change ◽  
Point Of View ◽  
Whole Body ◽  
High Dose ◽  
X Rays ◽  
Long Term Effects ◽  
Ionizing Radiations ◽  
Percentage Incidence

The causes of death in mice exposed at the age of 30 days to a single whole-body dose of 15 MeV X-rays have been analyzed from the point of view of both percentage incidence and distribution in time. Ten groups of death causes were used, based on post-mortem findings. In the lower dose groups (50 to 457 r), the percentage incidence was found, in most cases, to vary very little with dose, but some diseases, e. g. leukaemia, did show a definite increase, and others, e. g. pulmonary tumours, a definite decrease with increasing dose. The changes in incidence were linearly related to the dose. The analysis of survival curves for each cause of death separately has revealed that while all causes were advanced by radiation, some were advanced more than others. A definite correlation was found between the acceleration of a given cause of death and the rate of change of the percentage incidence with dose. This suggests that the change of incidence is merely the result of the changed times of onset of disease; an actuarial correction has confirmed this suggestion. It is concluded that the probability of any one disease occurring remains the same in irradiated as in the control animals, the main effect of the radiation being an advancement, at different rates, of all causes of death. The age of the animal at irradiation may be an important factor in deter­mining the relative acceleration of the different diseases. In the high dose groups (549 to 780 r) a definite decrease in incidence of neoplastic diseases has been established. This may be due to a 4 'radiotherapeutic’ effect in cells which later in life might have become manifest as neoplasms.

scholarly journals Effects of Prometryn Exposure Scenarios on Microcystis aeruginosa Growth and Water Qualities in Incubator Experiments

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1346
Author(s):  
Zhenjiang Yang ◽  
Suiliang Huang ◽  
Xiaowen Huang ◽  
Xiaofu Liang ◽  
Waseem Akram ◽  
...  
Keyword(s):  
Microcystis Aeruginosa ◽  
Growth Rates ◽  
Biological Effects ◽  
High Dose ◽  
Single Exposure ◽  
Time Of Application ◽  
Maximum Inhibition ◽  
Nutrient Consumption ◽  
Exposure Pattern ◽  
Significant Factors

Although multiple herbicide exposures are more prospective to occur in water, many previous studies were carried out as single herbicide exposure. To investigate the toxic effect of prometryn on cyanobacteria and water qualities, single and double prometryn exposures (at different growth phases) on Microcystis aeruginosa growth and concentrations of nutrients were compared after a 44-day experiment. Results indicated that under single exposure, maximum inhibition rates were 4.7–12.0% higher than those under double exposures. Correspondingly, the maximum Microcystis aeruginosa densities and growth rates under single exposure were 10.3–21.1% and 19.5–37.7% lower than those under double exposures (p < 0.05), respectively. These findings revealed that repeated prometryn exposures resulted in a reduction in biological effects, because the time of application and the concentration injected during the first application were both significant factors in the biological effects of prometryn. Prometryn exposure scenarios did not have a significant effect on nutrient or nutrient consumption concentrations (p > 0.05). In general, the pattern of nutrient limitation showed a shift from phosphorus to nitrogen limitation. The quantified relationships between Microcystis aeruginosa growth rates and consumed nutrients were studied. Based on the above findings, we believe that a high-dose and single prometryn exposure is a more effective exposure pattern for limiting cyanobacteria growth.

scholarly journals MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e046225
Author(s):  
Sarah Brown ◽  
Debbie Sherratt ◽  
Samantha Hinsley ◽  
Louise Flanagan ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Plasma Cell ◽  
Phase Ii ◽  
Whole Body ◽  
Cell Leukaemia ◽  
High Dose ◽  
Newly Diagnosed ◽  
Genetic Changes ◽  
Novel Treatment

IntroductionMultiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.Methods and analysisThe Myeloma UK nine OPTIMUM trial (MUKnine) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUKnine a), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUKnine b) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUKnine b primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.Ethics and disseminationEthics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN16847817, May 2017; Pre-results.

scholarly journals Early and Late Cytologic Effects of Whole Body Irradiation on Human Marrow

Blood ◽  
1964 ◽  
Vol 23 (4) ◽  
pp. 471-487 ◽  
Author(s):  
T. M. FLIEDNER ◽  
GOULD A. ANDREWS ◽  
EUGENE P. CRONKITE ◽  
VICTOR P. BOND
Keyword(s):  
Dose Group ◽  
Animal Experiments ◽  
Giant Cells ◽  
Whole Body ◽  
High Dose ◽  
Multinucleated Cells ◽  
Exposed Individual ◽  
Interphase Cells ◽  
Cytologic Abnormalities ◽  
Dose Dependent

Abstract 1. Serial marrow studies were performed during the first few days in eight men accidentally exposed to a mixed neutron gamma irradiation. They showed the occurrence of a wave of cytologic abnormalities. These were identical with those seen in animal experiments 1-3 days after whole body irradiation. They were considered to be "mitotically connected" (M. C. Abn.) and included the occurrence of chromosomal bridges and chromosomal fragments in mitoses. In interphase cells, the main abnormalities were nuclear fragments ("karyomeres") in the cytoplasm of erythroblasts, myelocytic cells and lymphocytes; bi- and multinucleated cells; and giant cells. The peak of abnormalities in the erythropoietic forms was reachéd after 2 days; that in the myelopoietic cells 4 days after exposure. On the 4th day, there was a distinct dose-dependent difference in these abnormalities between the high dose group (236-365 rads) and the low dose group (22-68 rads). 2. Some cytologic abnormalities, as seen in increased regeneratory activity of the marrow, were found in marrow smears 3.5 years after the accident, although the peripheral blood counts and mitotic indices of the marrow were within normal range. Their significance is obscure. 3. A careful cytologic evaluation of serially aspirated marrow samples during the first hours and days after whole body exposure proves to be an additional important aid in the assessment of the exposed individual and may well prove to be useful in determining the degree of injury and thus the prognosis.

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

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