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PubMedDate not supplied

Combined radiation sensitizing and anti-angiogenic effects of ionizing radiation and the protease inhibitor ritonavir in a head and neck carcinoma model.

Ritonavir, a protease inhibitor, has been successfully applied in the treatment of HIV infection. Reports of dramatic improvement of AIDS-related cancers, such as primary central system lymphoma after radiation therapy as well as Kaposi's sarcoma, led to the recent discovery of the "non viral" antitumor activity of HIV protease inhibitors. This study was designed to detect the antitumor effect of Ritonavir when combined with ionizing radiation both in vitro and in vivo in the HEP-2 head and neck carcinoma model. Inhibition of tumor growth was observed when mice were treated with Ritonavir alone and this effect was enhanced when combined with ionizing radiation. No adverse effect or significant toxicity in the hosts' body weights was seen between the different treatment and control groups throughout the experiments. A marked antiproliferation effect of the combination was observed in vitro. A marked reduction of angiogenesis was detected within the tumor sections from the Ritonavir combined with irradiation group as compared with the Ritonavir or irradiation alone groups. Western blot analysis showed that apoptosis was induced by an increased expression of Bax and decreased expression of Bcl-2 after treatment with Ritonavir and ionizing radiation. Thus, the antitumor effect of the latter combination is associated with the enhancement of radiation-induced apoptosis and inhibition of angiogenesis. These data suggested that Ritonavir could clinically improve the tumor response to radiation therapy, especially in head and neck carcinoma.

Animals↗
PubMedDate not supplied

[The efficiency of the radiobiological and clinical of the intraoperative radiation therapy in combination with distant gamma-radiation therapy of malignant tumors].

The efficiency of the radiobiological and the clinical planning of the combination of the intraoperative radiation therapy (IORT) and the external beam radiation therapy (EBRT) was assessed according to the incidence of local recurrences and to the level of radiation-induced damages during 5 years for patients with malignant tumors of head and neck, lung and soft tissues. Criteria of radiobiological planning for performing IORT + EBRT using the modified model of TDF (time-dose-fractionation) for calculating a single IORT dose and total radiation doses was defined among 169 patients of the studied group. The control group included 115 patients who were treated with surgery followed by photon radiation therapy at the total dose of 40-45 Gy. The Clinical critetia for performing the combined treatment with IORT and EBRT were such like: locally-advanced tumors, multicentrical location of tumor sites and the necessity of the increasing of the total doses of the combination of IORT and EBRT. The Average rates of total doses of IORT and EBRT were 67 +/- 2.1 Gy for patients with cancer of nasal cavity and of accessory nasal sinus, 50 +/- 1.8 Gy for patients with oral cavity cancer, 60 +/- 0.7 Gy for patients with lung cancer and 75 +/- 2.0 Gy for patients with sarcomas of soft tissues. Radiation-induced damages for normal tissues such as mandible osteomyelitis, neuritis and pathological bone fracture occurred among 16.8% of patients from the studied group if the TDF factor was exceeded over 100 conventional units. The combined treatment with IORT and EBRT resulted the significant reduction of recurrence rate among 5-year as compared with the combined treatment fot the control group: 37.5 +/- 5.3% and 65 +/- 5.1% of patients with cancer of nasal cavity and accessory nasal sinus; 55.8 +/- 6.3% and 80 +/- 5.9% of patients with oral cavity cancer; 57.8 +/- 6.7% and 75 +/- 5.8% of patients with non-small cell lung cancer and 32.7 +/- 6.1% and 72 +/- 6.7% of patients with sarcomas of soft tissues, respectively. The use of criteria for radiobiological and clinical planning of the combined treatment with IORT and EBRT promotes the improvement of long-term treatment results.

Combined Modality Therapy↗
PubMed2006

Enhancement of radiation sensitivity, delay of proliferative recovery after radiation and abrogation of MAPK (p44/42) signaling by imatinib in glioblastoma cells.

Glioblastomas are intrinsically resistant to conventional radiation therapy. The present study investigated the possibility that the tyrosine kinase inhibitor, imatinib, could enhance radiation sensitivity and influence proliferative recovery after irradiation in glioblastoma cells. Radiosensitivity was evaluated by clonogenic survival; apoptotic cell death was evaluated using flow cytometric analysis; proliferative recovery was monitored based on viable cell number subsequent to radiation-induced growth arrest; activation of p44/42 MAPK was based on phosphorylation of the protein. Glioblastoma cells pretreated with imatinib demonstrated an enhanced sensitivity to radiation. Imatinib also delayed proliferative recovery in irradiated glioblastoma cells. Imatinib promoted suppression of p44/42 MAPK signaling both when added prior to and post-irradiation. Increased sensitivity to radiation and delayed proliferative recovery in irradiated glioblastoma cells exposed to imatinib may be a consequence of the capacity of imatinib to interfere with p44/42 MAPK kinase signaling. Imatinib may prove to have clinical utility as a neoadjuvant and adjuvant in the treatment of glioblastomas that receive radiation therapy.

Antineoplastic Agents↗
PubMed1990

Radiation-induced osteosarcoma in dogs after external beam or intraoperative radiation therapy.

This report describes radiation-induced osteosarcomas in two groups of dogs. One group was given radiation therapy for spontaneous tumors and the second group of normal adult beagle dogs was given experimental intraoperative radiation therapy. Secondary tumors developed between 1.7 to 5 years after irradiation. Three of 87 spontaneous tumor-bearing dogs or 3.4% of dogs treated for soft tissue sarcomas developed osteosarcoma within the field of irradiation. Twenty-two dogs or 25% of dogs treated for soft tissue sarcomas survived 20 months. This high incidence may be due to the use of fractions in excess of 3.5 Gy. These dogs received 10 fractions in 3 weeks with fractions ranging from 3.5 to 5.0 Gy. Tumor induction may be included in the late effects of irradiation which are worsened by the use of coarse fractionation. There appeared to be a dose relationship for tumors induced after single intraoperative radiation doses combined with fractionated external beam irradiation. Seven of 27 dogs given this treatment and surviving at least 4 years developed osteosarcomas in the field of irradiation. One of 26 dogs given intraoperative radiation alone developed a tumor between 4 and 5 years. The lower incidence after intraoperative radiation alone may have been due to the lower total dose. However, the sequence of a course of fractionated irradiation followed by a large single dose seemed to enhance carcinogenicity.

Animals↗
PubMed1989

[The diagnosis, clinical picture and treatment of acute radiation sickness in the victims of the Chernobyl Atomic Electric Power Station. II. Non-bone marrow syndromes of radiation lesions and their treatment].

Out of 115 victims to the breakdown, 56 persons had radiation burns, 17 the intestinal syndrome, 80 the oropharyngeal syndrome, and 7 interstitial radiation pneumonitis. In the lethal outcome, of crucial importance were radiation burns (over 40% of the body surface) (19 persons) and radiation pneumonitis (7 persons). The grave intestinal and oropharyngeal syndromes were accompanied by other fatal manifestations of radiation injuries. Hemoperfusion, plasmapheresis, continuous heparinization and administration of freshly frozen plasma did not bring about any improvement. The local use of different remedies under aseptic conditions was the leading method of the treatment of radiation burns in the acute period. Parenteral feeding turned out to produce a beneficial effect in the treatment of the intestinal and oropharyngeal syndromes.

Accidents↗
PubMed1996

Synchrotron radiation in the study of the variation of dose response in thermoluminescence dosimeters with radiation energy.

Thermoluminescence dosimetry (TLD) is a versatile technique with many applications for dosimetry of ionising radiation. However, in the range of kilovoltage x-rays which is widely used for diagnostic and therapeutic medical applications, problems arise from the differing dose response of most TL dosimeters with the radiation energy. The dose response of various TL detector types was investigated in mono-energetic x-ray beams of 26.8, 33.2, 40, 80.4 and 99.6keV from a synchrotron radiation source at the National Laboratory for High Energy Physics in Japan. This response was studied as a function of TL material (LiF:Mg,Ti, LiF:Mg,Cu,P and Al2O3), the detector geometry and size, and their thermal history. Due to the asymmetric diffraction from a Si crystal employed to produce monoenergetic photons there was more than 50% dose inhomogeneity in some of radiation fields used. Therefore, the different TL dosimeter types were rotated around and the results related to the reading of a set of "standard" LiF:Mg,Ti ribbons which were included in all experiments as reference detectors. No significant influence of the detector shape (physical size, thickness) on the dose response with energy could be found. However, the pre-irradiation thermal history influences the dose response with radiation energy: a fast cool down of LiF:Mg,Ti after a high temperature anneal will increase the sensitivity by more than a factor of two. The relatively new TLD material LiF:Mg,Cu,P (GR-200, obtained from Solid Dosimeter & Detector Laboratories, Beijing) was found to be approximately 100 times more sensitive than the standard LiF:Mg,Ti. In addition it proved to be more tissue equivalent for photon radiation between 27keV and 40keV. The performance of LiF:Mg,Cu,P makes it a very interesting TL material deserving further evaluation for applications in diagnostic and therapeutic x-rays.

Aluminum Oxide↗
PubMed1977

Radiation toxicology: quantitative radiation pathology for predicting effects.

Radiation toxicology is the quantification of radiation pathophysiology. It is based upon the development of more precise and accurate radiation dose response data in humans. Such information is particularly important because of the development of combined radiation therapy and chemotherapy. The search for models which will predict radiation injury is presented along with innovative approaches to the 3-dimensional reconstruction of isodose curves in autopsy material, and ultrastructural studies.

Animals↗
PubMed2002

Radiation-induced health effects on atmospheric flight crew members: clues for a radiation-related risk analysis.

There are few human data on low-dose-rate-radiation exposure and the consequent acute and late effects. This fact makes it difficult to assess health risks due to radiation in the space environment, especially for long-term missions. Epidemiological data on civilian flight personnel cohorts can provide information on effects due to the low-dose and low-dose rate mixed high- and low-LET radiation environment in the earth's atmosphere. The physical characteristics of the radiation environment of the atmosphere make the results of the studies of commercial flight personnel relevant to the studies of activities in space. The cooperative international effort now in progress to investigate dose reconstructions will contribute to our understanding of radiation risks for space exploration.

Aerospace Medicine↗
PubMedDate not supplied

Analysis of radiation scatter during angiographic procedures: evaluation of a phantom model and a modified radiation protection system.

PURPOSE: To study the radiation scattering associated with the digital subtraction angiography (DSA) unit in angiographic procedures and to design an effective radiation protection shield based on these data. MATERIALS AND METHODS: The number of scattered photons was measured at three points relative to the operator's position. Anteroposterior abdominal and lateral cranial fluoroscopy were evaluated. As protective devices, a lead curtain, sliding shields, and a brim-shaped image intensifier (II) hood were designed. RESULTS: In abdominal fluoroscopy, radiation was found to scatter to the operator's lower limbs from the underside of the catheter table, to the abdomen from the side of the patient's body, and to the head and neck from the table surface adjacent to the patient. The use of protective devices reduced exposure from 2.89 to 0.058 mR/min for the operator's lower limbs, from 0.987 to 0.069 mR/min for the operator's abdomen, and from 0.696 to 0.139 mR/ min for the operator's head and neck area. With lateral cranial fluoroscopy, radiation was detected to scatter to the operator's lower limbs from the underside of the catheter table, to the abdomen from the patient's temporal area, and to the head and neck from the patient's face. The use of protective devices reduced exposure from 0.248 to 0.010 mR/min for the operator's lower limbs, from 0.129 to 0.010 mR/min for the operator's abdomen, and from 0.162 to 0.018 mR/min for the operator's head and neck area. CONCLUSIONS: The characteristic directions of scattering to the operator were identified. An effective modified radiation protection system was designed based on this information.

Abdomen↗
PubMed2006

Low doses of ionizing radiation can prevent radiation-induced colonic epithelial hyporesponsiveness to muscarinic agonists.

PURPOSE: Colonic epithelium hyporesponsiveness to different secretagogues occurs after exposure to ionizing radiation, increasing susceptibility to bacterial translocation and intraluminal toxins. Growing evidence suggests that the biological effects of radiation might be hormetic in nature. We investigated if exposure to low doses of ionizing radiation (LDR) can prevent colon hyposecretion due to subsequent larger doses. METHODS: Rats were exposed to LDR (0.05 Gy) 24 h prior to 6 Gy, high dose radiation (HDR). The cyclic adenosine monophosphate (cAMP)-mediated pathway was explored using forskolin (FSK) and the intracellular Ca2+-mediated pathway through cholinergic stimulation. Changes in the colonic epithelium at the ultrastructural level were also explored. RESULTS: Maximal short circuit current (Isc) response to carbachol was significantly reduced in the group exposed to 6 Gy HDR and this was completely prevented by prior exposure to LDR. Responses to both FSK and electrical field stimulation (EFS) were significantly reduced after HDR but they were not prevented by prior adaption of LDR. Hyposecretion was not prevented by the inducible nitric oxide synthase (iNOS) inhibitor L-N6-(l-iminoethyl)lysine (L-NIL) ruling out a role for iNOS-derived nitric oxide (NO) in the colonic hyposecretion associated with whole body radiation. Prior exposure to LDR diminished the deleterious effect of full HDR on the ultrastructure of colonic epithelium as colonocytes vacuolization, microvilli lost and separation between neighboring cells were less evident. CONCLUSIONS: Previous exposure to LDR can prevent intracellular Ca2+-mediated colonic hyposecretion associated with exposure to HDR but fails to modify cAMP-mediated hyposecretion. Morphological damage at the ultrastructural level is less evident after prior LDR.

Animals↗
PubMed1988

Trends in radiation protection--a view from the National Council on Radiation Protection and Measurements (NCRP).

The present status of ionizing radiation protection in our society, with the exception of extraordinary events such as the Chernobyl accident, can be considered reasonably satisfactory. Occupationally, average exposures have risks no greater than accident rates in "safe" industries and show a downward trend in concert with results of safety practices in other occupations; higher exposures are being addressed specifically, and a new NCRP guideline may prove useful. An important concern relating to the quality factor for neutrons is at least partially accounted for by recent International Commission on Radiological Protection (ICRP) and NCRP recommendations. Among public exposures, the most important by far is exposure to indoor Rn. However, this problem is being addressed on all fronts, and its magnitude and the means to deal with it will soon be better known. For the near future, we should see a stabilizing of risk estimates, albeit at levels very probably higher than formerly. There may also be an increasing tendency to use incidence rather than mortality for calculating these estimates. These changes may require some adjustment in our perspective on limits. As the difference in risk between the sexes becomes more definite, we may wish to adopt a policy of equal risk rather than one of equal dose. Age data also emphasize, more and more, the decline of risk with age; consequently, using older workers when feasible in radiation-exposure circumstances becomes more desirable. For the longer-term future, various developments can be expected, including, possibly, a more suitable climate for a risk system, a more appropriate way to express differences in radiation quality, further knowledge of the role probabilities of causation may play in radiation control, the effect of mitigating and enhancing factors, and progress in fundamental oncology. All of these are exciting possibilities which may provide a variety of options for the most effective radiation protection in the future.

Accidents↗
PubMed1989

Relationship between kidney burden and radiation dose from chronic ingestion of U: implications for radiation standards for the public.

Metabolic models for U in adults recommended by Wrenn et al. (1985) and the International Commission on Radiological Protection (ICRP 1979a) were used to study the relationship between kidney burden and radiation dose from chronic ingestion of soluble 238U or natural U and whether current radiation standards for the public provide adequate protection against chemical toxicity from U in the kidney. We assumed that the threshold concentration for chemical toxicity is 1 microgram of U g-1 of kidney and that a safety factor of 10 should be applied in limiting kidney burdens for maximally exposed individuals in the general public. We found that a limit on annual effective dose equivalent of 1 mSv (0.1 rem) for chronic exposures of the public from all sources, as recommended by the ICRP (1985) and the National Council on Radiation Protection and Measurements (NCRP 1987), corresponds to concentrations of U in the kidney from chronic ingestion that exceed the assumed threshold for chemical toxicity of 1 microgram g-1 only for 238U using the metabolic model of the ICRP (1979a). However, using either metabolic model (ICRP 1979a; Wrenn et al. 1985), the predicted concentrations of U in the kidney exceeded the limit of 0.1 microgram g-1, based on the assumed safety factor for protection of the public, for both 238U and natural U. From these results, we concluded that chemical toxicity should be considered in developing health protection standards for the public for ingestion of soluble 238U or natural U. Environmental radiation standards for certain practices established by the U.S. Environmental Protection Agency and Nuclear Regulatory Commission (EPA 1987a, 1987b, 1987c, 1987d; NRC 1988a) are consistent with a limit on annual effective dose equivalent of 0.25 mSv (25 mrem) per practice. If the metabolic model of Wrenn et al. (1985) is assumed to be appropriate for chronic ingestion of soluble U in the environment, then the dose limit of 0.25 mSv corresponds to a concentration of 238U or natural U in the kidney that is below the assumed limit of 0.1 microgram g-1 for members of the public. Inhalation of soluble and insoluble U and ingestion of insoluble U were considered. Except for inhalation of soluble U, these modes of intake reduced predicted concentrations in the kidney per unit effective dose equivalent compared with values for ingestion of soluble U. Unresolved issues of importance for determining the significance of chemical toxicity relative to radiation dose in establishing limits on public exposures for U also are discussed.

Adult↗
PubMed1995

Application of the HSEF to assessing radiation risks in the practice of radiation protection.

The primary risk coefficients upon which exposure limits for radiation protection purposes are currently based are derived almost exclusively from cancer-induction data obtained from human populations exposed to radiations of low linear energy transfer. The question of higher linear energy transfer radiations is handled by means of quality factors derived from values for relative biological effectiveness obtained from animal data. However, the advent of microdosimetry has made it possible to establish hit size effectiveness functions from single-cell systems, both in vitro and in vivo. This type of function can substitute completely for the concept of relative biological effectiveness, Q and equivalent dose. A common basis for risk coefficients and the hit size effectiveness function lies in the fact that human cancers are monoclonal and thus single cell in origin. The present communication utilizes this common base as a means of extending the present low-linear energy transfer based risk coefficients to include carcinogenic responses from exposure in radiation fields of any one or mixed qualities, extending from the smallest to the largest linear energy transfers of practical consequence. In doing so, risks from ionizing radiations of any linear energy transfer may be predicted more accurately than at present.

Biophysical Phenomena↗
PubMed1981

Hanford radiation study III: a cohort study of the cancer risks from radiation to workers at Hanford (1944-77 deaths) by the method of regression models in life-tables.

This paper reports on results from the study initiated by Mancuso into the health risks from low-level radiation in workers engaged in plutonium manufacture at Hanford Works, Washington State, USA, and attempts to answer criticisms of previous reports by an in-depth study. Previous reports have aroused much controversy because the reported risk per unit radiation dose for cancers of radiosensitive tissues was much greater than the risk generally accepted on the basis of other studies and widely used in setting safety levels for exposure to low-level radiation. The method of regression models in life-tables isolates the effect of radiation after statistically controlling for a wide range of possible interfering factors. Like the risk of lung cancer for uranium miners the dose-response relation showed a significant downward curve at about 10 rem. There may, therefore, be better agreement with other studies, conduct at higher doses, than is widely assumed. The findings on cancer latency (of about 25 years) and the effect of exposure age (increasing age increases the risk) are in general agreement with other studies. An unexplained finding is a significantly higher dose for all workers who developed cancers in tissues that are supposed to have low sensitivity to cancer induction by radiation.

Actuarial Analysis↗
PubMed2002

Radiation Research Society. 1952-2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells?

Around 30 years ago, a very prominent molecular biologist confidently proclaimed that nothing of fundamental importance has ever been learned by irradiating cells! The poor man obviously did not know about discoveries such as DNA repair, mutagenesis, connections between mutagenesis and carcinogenesis, genomic instability, transposable genetic elements, cell cycle checkpoints, or lines of evidence historically linking the genetic material with nucleic acids, or origins of the subject of oxidative stress in organisms, to name a few things of fundamental importance learned by irradiating cells that were well known even at that time. Early radiation studies were, quite naturally, phenomenological. They led to the realization that radiations could cause pronounced biological effects. This was followed by an accelerating expansion of investigations of the nature of these radiobiological phenomena, the beginnings of studies aimed toward better understanding the underlying mechanisms, and a better appreciation of the far-reaching implications for biology, and for society in general. Areas of principal importance included acute tissue and tumor responses for applications in medicine, whole-body radiation effects in plants and animals, radiation genetics and cytogenetics, mutagenesis, carcinogenesis, cellular radiation responses including cell reproductive death, cell cycle effects and checkpoint responses, underlying molecular targets leading to biological effects, DNA repair, and the genetic control of radiosensitivity. This review summarizes some of the highlights in these areas, and points to numerous examples where indeed, many things of considerable fundamental importance have been learned by irradiating cells.

Animals↗
PubMed2004

Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group.

Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries. Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes. Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis. Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome. Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation. Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents. Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends. Treatment of pregnant women must account for risk to the fetus. For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.

Animals↗
PubMedDate not supplied

Radiation pneumonitis following multi-field radiation therapy.

The mechanisms of radiation pneumonitis have not been established. In a study on multi-field radiation therapy for lung cancer, one patient developed severe radiation pneumonitis even though the target volume was small. Radiation therapy was performed at a dose of 75 Gy in 50 fractions over five weeks. High-density areas conforming to the radiation field were observed by high-resolution CT. They were observed in the irradiated volume at doses under 20 Gy in the contralateral lung as well as in the ipsilateral lung.

Aged↗
PubMedDate not supplied

[Current epidemiological evidence regarding the health effects of low-dose ionizing radiation. Implications for radiation protection, public health and forensic medicine].

The health effects of low-dose ionizing radiation have been widely studied, but remain uncertain. Up-to-date knowledge about epidemiologic evidence for potential human health effects of low dose ionizing radiation is important for revising national radiation protection legislation. This review, conducted by a multidisciplinary research team of the Italian Institute of Social Medicine, evaluates epidemiologic studies published since July 2003. After careful selection, a total of 302 studies were reviewed. Greater emphasis was given to papers that analyzed data using standardized incidence and mortality ratios and to studies regarding occupational exposures in all workers, healthcare workers and aircrew members. Nevertheless, studies regarding A-bomb survivors of Hiroshima/Nagasaki, Chernobyl cleanup workers, patients exposed for medical reasons, and workers in nuclear plants were also included. Given the limitations of epidemiological studies and excluding the cosmic rays context, which requires further research, the authors conclude that harmful effects from exposures to ionizing radiation at doses lower than 100 mSv cannot be ruled out. Nevertheless, if any harmful health effects do exist, they are certainly very small. The implications for radiation protection, public health and forensic medicine are discussed.

Humans↗