Radiation treatment decreases bone cancer pain, osteolysis and tumor size

Radiotherapy is the cornerstone of palliative treatment for primary bone cancer in animals and metastatic bone cancer in humans. However, the mechanism(s) responsible for pain relief after irradiation is unknown. To identify the mechanism through which radiation treatment decreases bone cancer pain, the effect of radiation on mice with painful bone cancer was studied. Analysis of the effects of a 20-Gy treatment on localized sites of painful bone cancers was performed through assessments of animal behavior, radiographs and histological analysis. The findings indicated that radiation treatment reduced bone pain and supported reduced cancer burden and reduced osteolysis as mechanisms through which radiation reduces bone cancer pain.     

The Antioxidant,MnTE-2-PyP,Prevents Side-Effects Incurred by Prostate Cancer Irradiation

Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well. Potential side-effects due to prostate cancer-related radiation therapy include bowel inflammation, erectile dysfunction, urethral stricture, rectal bleeding and incontinence. Currently, radiation therapy for prostate cancer does not include the administration of therapeutic agents to reduce these side effects and protect normal tissues from radiation-induced damage. In the current study, we show that the small molecular weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin, prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected from erectile dysfunction, a persistent problem regardless of the type of radiation techniques used because the penile neurovascular bundles lay in the peripheral zones of the prostate, where most prostate cancers reside. Based on previous studies showing that MnTE-2-PyP, in combination with radiation, further reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an excellent radioprotectant in combination radiotherapy for cancer in general and specifically for prostate cancer.     

The localization of 125iodide, 3H-inulin and 3H-acetylcholine in autoradiographic model experiments

Summary Autoradiographic experiments are described in which low and high molecular radioactive compounds with different types of radiation are used. The effect of the following procedures on the spread of grains were studied: 1) cutting-direction, 2) diffusion of molecules at cryostate temperatures, 3) the type of radiation, 4) time lapse between dissection and freezing of the tissue.It is suggested that the resolution with ¹²⁵Iodine-labeled compounds is worse than with tritium-labeled compounds, owing to different radiation.     

Molecular mechanisms of radiation carcinogenesis and the linear, non-threshold dose response model of radiation risk estimation

Recent research in molecular radiation carcinogenesis is reviewed with the specific aim of exploring the implications this research may have on the dose response relationship of radiation-induced cancer at low doses and low dose rates. It is concluded that the linear non-threshold dose response hypothesis may be used in radiation protection planning as a simple, convenient method to optimize procedures and regulations, but should not be mistaken as a stringent scientific conclusion directly derived from the present state of knowledge of the processes involved in radiation carcinogenesis.     

Nanoscale spatial induction of ultraviolet photoproducts in cellular DNA by three-photon near-infrared absorption

The high-resolution spatial induction of ultraviolet (UV) photoproducts in mammalian cellular DNA is a goal of many scientists who study UV damage and repair. Here we describe how UV photoproducts can be induced in cellular DNA within nanometre dimensions by near-diffraction-limited 750 nm infrared laser radiation. The use of multiphoton excitation to induce highly localized DNA damage in an individual cell nucleus or mitochondrion will provide much greater resolution for studies of DNA repair dynamics and intracellular localization as well as intracellular signalling processes and cell–cell communication. The technique offers an advantage over the masking method for localized irradiation of cells, as the laser radiation can specifically target a single cell and subnuclear structures such as nucleoli, nuclear membranes or any structure that can be labelled and visualized by a fluorescent tag. It also increases the time resolution with which migration of DNA repair proteins to damage sites can be monitored. We define the characteristics of localized DNA damage induction by near-infrared radiation and suggest how it may be used for new biological investigations.     

Marine disposal of radioactive wastes

In a general sense, the main attraction of the marine environment as a repository for the wastes generated by human activities lies in the degree of dispersion and dilution which is readily attainable. However, the capacity of the oceans to receive wastes without unacceptable consequences is clearly finite and this is even more true of localized marine environments such as estuaries, coastal waters and semi-enclosed seas. Radionuclides have always been present in the marine environment and marine organisms and humans consuming marine foodstuffs have always been exposed, to some degree, to radiation from this source. The hazard associated with ionizing radiations is dependent upon the absorption of energy from the radiation field within some biological entity. Thus any disposal of radioactive wastes into the marine environment has consequences, the acceptability of which must be assessed in terms of the possible resultant increase in radiation exposure of human and aquatic populations. In the United Kingdom the primary consideration has been and remains the safe-guarding of public health. The control procedures are therefore designed to minimize as far as practicable the degree of human exposure within the overall limits recommended as acceptable by the International Commission on Radiological Protection. There are several approaches through which control could be exercised and the strengths and weaknesses of each are considered. In this review the detailed application of the critical path technique to the control of the discharge into the north-east Irish Sea from the fuel reprocessing plant at Windscale is given as a practical example. It will be further demonstrated that when human exposure is controlled in this way no significant risk attaches to the increased radiation exposure experienced by populations of marine organisms in the area.     

RADIATION: MEDICAL DIAGNOSTIC USES

Use of radiologic procedures in diagnosis now contributes a significant dose of ionizing radiation to our population. Whether this presents a real risk to the health of the present and future population cannot be determined with certainty from evidence available at this time. Hence, it appears proper to keep the dose to every patient as low as practical consistent with good medical practice. The average dose can be significantly reduced by having more physicians apply the known techniques for minimizing the exposure to the patient.The medical profession has a direct professional concern for the actual or potential risk of damage resulting from the radiation that patients are exposed to during diagnostic x-ray procedures, since these procedures constitute the largest single man-made source of genetically significant radiation our population is now exposed to.It is important to distinguish two distinctly different types of radiation effects—somatic effect, in which the damage affects the health of the person irradiated, and genetic effect that is capable of producing constitutional defects in future progeny over many generations.     

Selecting treatment for high-risk, localized prostate cancer: the case for radical prostatectomy

The most common treatment options for men with clinically localized prostate cancer include radical prostatectomy and radiation therapy. The choice between these options is often controversial, and selecting the optimal treatment poses a great challenge for patients and physicians. Factors important to the decision include age and life expectancy of the patient, the natural history of the prostate cancer, how curable the disease is, and the morbidity of treatment. Use of these criteria to select treatment for a healthy, 70-year-old man presenting with a nonpalpable tumor, stage T1c disease, serum prostate-specific antigen of 12 ng/mL, and an adenocarcinoma with a Gleason score of 8 that is present in 2 of 12 biopsy cores would lead to the choice of radical prostatectomy over radiation therapy. Data show that such a patient has a life expectancy of more than 12.3 years if the prostate cancer can be cured and a high probability of dying from the disease if it is not cured. Data further show that radical prostatectomy in such a patient would confer a survival advantage over radiation therapy without resulting in greater complications or reduction in quality of life.     

Management of clinically localized prostate cancer

Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer.     

Risk of whole body radiation exposure and protective measures in fluoroscopically guided interventional techniques: a prospective evaluation

BACKGROUND: Fluoroscopic guidance is frequently utilized in interventional pain management. The major purpose of fluoroscopy is correct needle placement to ensure target specificity and accurate delivery of the injectate. Radiation exposure may be associated with risks to physician, patient and personnel. While there have been many studies evaluating the risk of radiation exposure and techniques to reduce this risk in the upper part of the body, the literature is scant in evaluating the risk of radiation exposure in the lower part of the body. METHODS: Radiation exposure risk to the physician was evaluated in 1156 patients undergoing interventional procedures under fluoroscopy by 3 physicians. Monitoring of scattered radiation exposure in the upper and lower body, inside and outside the lead apron was carried out. RESULTS: The average exposure per procedure was 12.0 PlusMinus; 9.8 seconds, 9.0 PlusMinus; 0.37 seconds, and 7.5 PlusMinus; 1.27 seconds in Groups I, II, and III respectively. Scatter radiation exposure ranged from a low of 3.7 PlusMinus; 0.29 seconds for caudal/interlaminar epidurals to 61.0 PlusMinus; 9.0 seconds for discography. Inside the apron, over the thyroid collar on the neck, the scatter radiation exposure was 68 mREM in Group I consisting of 201 patients who had a total of 330 procedures with an average of 0.2060 mREM per procedure and 25 mREM in Group II consisting of 446 patients who had a total of 662 procedures with average of 0.0378 mREM per procedure. The scatter radiation exposure was 0 mREM in Group III consisting of 509 patients who had a total 827 procedures. Increased levels of exposures were observed in Groups I and II compared to Group III, and Group I compared to Group II.Groin exposure showed 0 mREM exposure in Groups I and II and 15 mREM in Group III. Scatter radiation exposure for groin outside the apron in Group I was 1260 mREM and per procedure was 3.8182 mREM. In Group II the scatter radiation exposure was 400 mREM and with 0.6042 mREM per procedure. In Group III the scatter radiation exposure was 1152 mREM with 1.3930 mREM per procedure. CONCLUSION: Results of this study showed that scatter radiation exposure to both the upper and lower parts of the physician's body is present. Protection was offered by traditional measures to the upper body only.     

Sequence, expression, and location of zebrafish frizzled 10

Members of the frizzled gene family encode seven-pass transmembrane proteins that function in the interpretation and reception of Wnt-mediated cell-cell communication events. To investigate frizzled function in early zebrafish development, we isolated the maternally contributed frizzled 10 (fz10) gene and localized it to linkage group 8 using radiation hybrid mapping. The cloned zebrafish fz10 is closely related to the fz10 group from other organisms. Zygotic expression of fz10 is observed in the posterior tail mesenchyme, dorsal neural tube, and different parts of the brain.     

Radiation Hazards Control in Survival Operations in the Event of a Nuclear War

The concepts of radiation protection in survival operations are explained, and procedures devised to control radiation hazards for the protection of the population and maintenance of the operating efficiency of survival operations personnel are presented.Radiation protection is a command function. The medical responsibility is to provide advice on the probable effects of radiation exposure in the light of existing knowledge of these effects in man.The major hazard is that of external exposure to penetrating gamma radiation. Radiation exposure guides indicate that persons may be exposed to not more than 100 r whole body radiation in a six-week period, or 200 r whole body radiation in a period in excess of six weeks, without loss of operational efficiency. Beta radiation from fallout deposited on skin or clothing may produce burns, but these injuries will not be incapacitating and can be controlled by simple procedures.The internal hazard is mainly from ingestion of food or water contaminated with radioactive material. For protection, only canned or packaged foods and water from covered or deep wells are consumed during the early days after a nuclear attack.     

Historical review of occupational exposures and cancer risks in medical radiation workers

Epidemiological studies of medical radiation workers have found excess risks of leukemia, skin and female breast cancer in those employed before 1950 but little consistent evidence of cancer risk increases subsequently. Occupational radiation-related dose-response data and recent and lifetime cancer risk data are limited for radiologists and radiologic technologists and lacking for physicians and technologists performing fluoroscopically guided procedures. Survey data demonstrate that occupational doses to radiologists and radiologic technologists have declined over time. Eighty mostly small studies of cardiologists and fewer studies of other physicians reveal that effective doses to physicians per interventional procedure vary by more than an order of magnitude. For medical radiation workers, there is an urgent need to expand the limited information on average annual, time-trend and organ doses from occupational radiation exposures and to assess lifetime cancer risks of these workers. For physicians and technologists performing interventional procedures, more information about occupational doses should be collected and long-term follow-up studies of cancer and other serious disease risks should be initiated. Such studies will help optimize standardized protocols for radiologic procedures, determine whether current radiation protection measures for medical radiation workers are adequate, provide guidance on cancer screening needs, and yield valuable insights on cancer risks associated with chronic radiation exposure.     

Radiation-inducible gene therapy

The radiation-inducible chimeric genetic construct Egr-TNF alpha introduced into human xenografts produces cytotoxicity of infected tumor cells resulting in tumor growth inhibition. The interaction between Egr-TNF and radiation is selectively cytotoxic for the tumor microvasculature resulting in vascular thrombosis and tumor necrosis. Gene therapy combined with radiation therapy offers great potential for the treatment of localized human cancers.     

Differential localization of von Willebrand factor, fibronectin and 13-HODE in human endothelial cell cultures

Von Willebrand factor (vWF), fibronectin (FN) and 13-hydroxy-octadecadienoic acid (13-HODE) are known to influence the regulation of the adhesive properties of vascular surfaces. In the present study vWF, FN and 13-HODE were comparatively localized in endothelial cells (EC) and in the extracellular matrix (ECM) produced by EC. An indirect immunofluorescent technique was applied to coverslips containing human EC cultures previously fixed and permeabilized following different procedures: A. Alcohol/acetone; B. Paraformaldehyde alone and C. Paraformaldehyde followed by Triton X-100. vWF was observed inside EC (A), on the ECM produced by EC (B) or in EC and ECM (C) depending on the fixation procedures used. FN was mainly localized in the ECM despite the fixation procedures employed. FN was only seen in relation to cell bodies after strong permeabilization (A). Under our experimental conditions 13-HODE was never found in ECM. This latter antigen was observed randomly dispersed in those preparations fixed with alcohol/acetone, indicating that it is probably extracted by this fixative. 13-HODE was detected in granular shaped structures in EC after permeabilization with detergent (C). These results suggest that the cellular localization of vWF and FN is compatible with an adhesive role related to the abluminal side of ECs. 13-HODE was readily observed after mild permeabilization. This finding would be morphologically consistent with its contribution to the regulation of the vessel wall thromboresistance.     

Immunohistochemical localization of vitamin D-dependent calcium-binding protein in duodenum,kidney, uterus and cerebellum of chickens

Summary Calcium-binding protein (CaBP) has been localized with the immunoperoxidase method using antiserum against purified chick duodenal CaBP. Different preparative procedures were employed to investigate the experimental conditions possibly responsible for the contradictory reports in the literature of the precise cellular localization of CaBP. Freeze substitution, frozen sections followed by fixation and coagulant and non-coagulant fixatives were used with appropriate control sections to demonstrate that the true localization of CaBP in the chick duodenum is in the absorptive cell cytoplasm. The goblet cell localization reported in the literature seems to be a diffusion artifact due to inadequate fixation. CaBP was also localized in several other tissues. In the hen uterus, the tubular glands beneath the surface epithelium showed intense reaction. In the kidney, CaBP was present in the cells of the straight and convoluted segments of distal tubules. The cortex of the chick cerebellum showed the CaBP in Purkinje cells. The entire dendritic trees contained the reaction product. No other neurons in the molecular or the granular layer were stained. In the deep cerebellar nuclei, all neurons were negative and these were outlined by deeply staining axons of the Purkinje cells and their synaptic endings.     

Biological damage from the Auger effect,possible benefits

Summary Decay of radioactive isotopes by K-capture leads to the Auger effect and results in the loss of several orbital electrons and the emission of X-rays. Whereas radiation effects are produced from the emitted electrons, the consequences of the Auger effect are strictly localized to the site of the decaying nuclide.The paper reviews the biological consequences of the decay of¹²⁵I which produces the Auger effect. Nearly all data were obtained from DNA labeled with¹²⁵I-5-iodo-2-deoxyuridine (IUdR) in bacteria and mammalian cells. Parameters of effects were cell death, DNA strand breaks, and mutation induction. In order to recognize in a cell the contribution from the Auger effect and that of absorbed radiation, experimental data are analysed in terms of the specific energy for the nuclear volume which contains the isotope.The data indicate that decay of¹²⁵I is far more toxic than is expected on the basis of absorbed dose to the labeled nucleus. Moreover, it is emphasized that the toxicity of the¹²⁵I decay is largely determined by events immediately localized to the site of decay.Because the consequences of the Auger effect are strictly localized to the molecular site of the decay,¹²⁵I and perhaps other nuclides decaying by K-capture promise to be interesting tools in cell biology and molecular biology. First data on the Auger effect as a tool are summarized.It appears that recognizable biological damage is only observed when the Auger effect takes place in vitally important molecules, an example of which is DNA.Dedicated to Prof. Dr. H. Muth on the occasion of his 60th birthday.     

The human ubiquitin-activating enzyme E1 gene (UBE1) mapped to band Xp11.3----p11.23 by fluorescence in situ hybridization.

The human gene for ubiquitin-activating enzyme E1 (UBE1) was localized by a direct mapping system that combined fluorescence in situ hybridization with replicated R-bands on prometaphase chromosomes. The fluorescent signals were localized to Xp11.3----p11.23. Simple procedures for the detection of R-bands are also described.     

Higher patient doses through X-ray imaging procedures

Medical imaging using X-rays has been one of the most popular imaging modalities ever since the discovery of X-rays 125 years ago. With unquestionable benefits, concerns about radiation risks have frequently been raised. Computed tomography (CT) and fluoroscopic guided interventional procedures have the potential to impart higher radiation exposure to patients than radiographic examinations. Despite technological advances, there have been instances of increased doses per procedure mainly because of better diagnostic information in images. However, cumulative dose from multiple procedures is creating new concerns as effective doses >100 mSv are not uncommon. There is a need for action at all levels. Manufacturers must produce equipment that can provide a quality diagnostic image at substantially lesser dose and better implementation of optimization strategies by users. There is an urgent need for the industry to develop CT scanners with sub-mSv radiation dose, a goal that has been lingering. It appears that a new monochromatic X-ray source will lead to replacement of X-ray tubes all over the world in coming years and will lead to a drastic reduction in radiation doses. This innovation will impact all X-ray imaging and will help dose reduction. For interventional procedures, the likely employment of robotic systems in practice may drastically reduce radiation exposures to operators- but patient exposure will still remain an issue. Training needs always need to be emphasized and practiced.