Impact of pulmonary metastases of the R1H-tumour on radiation tolerance of rat lung

Purpose : The aim was to investigate the influence of pulmonary metastases of the rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat. Material and methods : Three groups of animals were investigated: metastases-free animals treated with fractionated irradiation of the lungs; metastases-bearing animals receiving no irradiation; and metastases-bearing animals treated with fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases were thus treated at various well-defined sizes. Total doses of 20-60Gy were applied in fractions of 2 Gy within 11 days. Complication rate and survival time were used as endpoints. Results : About 2 months after onset of irradiation treatment, animals had to be sacrificed because of severe respiratory distress either caused by irradiation-induced lung damage (median 57 days, range 36-77 days), or because of development of lung metastases (65, 20-160 days). A decrease of the ED 50 (dose required to induce lethal lung damage in 50% of irradiated animals) was determined for metastases-bearing animals. This effect increased with metastatic volume. Conclusions : The results suggest that the presence of tumours in the lung decreased the lung tolerance to radiation. This effect can hardly be explained by a reduction in functional lung volume by metastatic volume.     

First order correction for T2*‐relaxation in determining contrast agent concentration from spoiled gradient echo pulse sequence signal intensity

Purpose:

To investigate the accuracy of a method neglecting T₂*‐relaxation, for the conversion of spoiled gradient echo pulse sequence signal intensity to contrast agent (CA) concentration, in dynamic contrast enhanced MRI studies. In addition a new closed form conversion expression is proposed that accounts for a first order approximation of T₂*‐relaxation.

Materials and Methods:

The accuracy of both conversion methods is compared theoretically by means of simulations for four pulse sequences from literature. Both methods are tested in vivo against the numerical conversion method for measuring the arterial input function in mice.

Results:

Simulations show that the T₂*‐neglecting method underestimates typical tissue CA concentrations (0 mM to 2 mM) up to 6%, while the errors for arterial concentrations (0 mM to 10 mM) range up to 43%. The results from our first order method are numerically indistinguishable from the simulation input values in tumor tissue, while for arterial concentrations the error is reduced up to a factor 10. In vivo, peak Gd‐DOTA concentration is underestimated up to 14% with the T₂*‐neglecting method and up to 0.9% with our first order method.

Conclusion:

Our conversion method reduces the underestimation of CA concentration severely in a broad physiological concentration range and is easy to perform in any clinical setting. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Significance of manipulating intratumor hypoxia in the effect on lung metastases in radiotherapy,with reference to its effect on the sensitivity of intratumor quiescent cells

Purpose To evaluate the effect of manipulating intratumor hypoxia during radiotherapy on lung metastasis, referring to its effect on the sensitivity of quiescent tumor cells. Materials and Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following loading with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The sensitivity of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P + Q) tumor cell population was determined from BrdU non-treated tumors. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results In the total cells, a more marked enhancement in sensitivity was observed with nicotinamide than MTH. In Q cells, MTH combination induced a more marked enhancement than nicotinamide. Both nicotinamide and MTH reduced the size of the hypoxic fraction in the two cell populations, especially nicotinamide in the total cells and MTH in Q cells. Without γ-ray irradiation, nicotinamide loading tended to decrease the number of lung metastases. With γ-ray irradiation, nicotinamide loading and MTH, especially the former, reduced the number of metastases more than γ-ray irradiation only. Conclusion Hypoxia manipulation in solid tumors has the potential to influence lung metastases. Notably, acute hypoxia-releasing nicotinamide may be promising for reducing the number of lung metastases.     

Modélisation fonctionnelle adaptée à l’analyse des risques en radiothérapie

PurposeThis document presents a systematic and structured approach for functional modeling for risk analysis in radiotherapy, aiming to reconcile the need, on one hand, for a method that can be applied generally and, on the other hand, for a method that provides a highly precise model.Materials and methodsThe approach relies on new functional structuring patterns and flux analysis, derived from system engineering and knowledge engineering.ResultsThe method affords strong support for the development of detailed models of the patient's process through a department of radiotherapy. Lack of structure of the actual process in a particular department may be easily identified leading to the development of specific procedures for the improvement of security.ConclusionModeling approach derived from engineering may be used for functional modeling for risk analysis in radiotherapy.     

Effects of Whole-Body Gamma Irradiation and 5-Androstenediol Administration on Serum G-CSF

5-Androstenediol (5-AED) is a natural circulating adrenocortical steroid hormone that interconverts in vivo with other members of the 5-androstene family of steroids: dehydroepiandrosterone and 5-androstenetriol. These steroids stimulate immune responses and resistance to infection. 5-AED has been identified as a systemic radiation countermeasure that enhances survival in mice exposed to gamma irradiation and ameliorates radiation-induced neutropenia in mice and nonhuman primates. 5-AED mitigates radiation-induced decreases in platelets, natural killer (NK) cells, red blood cells, and monocytes. Administration of 5-AED causes functional activation of circulating granulocytes (phagocytic ability), monocytes (oxidative burst), and NK cells (surface CD11b expression). The effects of 5-AED on survival and hematological parameters are consistent with induction of hematopoietic cytokines. To test this hypothesis, we measured serum cytokines by ELISA, Luminex, and a cytokine array. A cytokine array was used for 62 different cytokines, chemokines, growth factors, and soluble receptors. 5-AED caused significant increases in circulating granulocyte colony-stimulating factor (G-CSF) in irradiated and unirradiated animals as observed with ELISA and Luminex. The cytokine array results suggest induction of G-CSF and additional cytokines, and related molecules. Since G-CSF is an important hematopoietic cytokine, the results support our hypothesis that the previously observed increases in numbers of hematopoietic progenitors, circulating innate immune cells and platelets, and functional activation of granulocytes, monocytes, and NK cells result from a cytokine cascade induced by 5-AED.     

DNA pattern of human pituitary tumors

The tumor tissue from 62 consecutive patients with pituitary adenomas was analyzed with regard to ploidy and percentage of cells in different phases of the cell cycle by use of flow-cytofluorometry. In six of 62 cases, two tumor-cell populations were identified; therefore the study material comprised 68 cell lines. Approximately half of the cell lines were diploid (33 of 68, or 49 per cent); five of 68 (7 per cent) were hypodiploid, and 30 of 68 (44 per cent) were hyperdiploid-aneuploid. A low occurrence of aneuploid cell lines appeared in hormonally nonsecreting tumors (22 per cent). An aneuploid DNA pattern was predominantly found in prolactinomas (70 per cent). In acromegaly, tumors secreting growth hormone had only an aneuploid DNA pattern in 41 per cent of the cases, whereas 67 per cent of the tumors with concomitant secretion of growth hormone and prolactin were aneuploid. The latter group also comprised the largest number of adenomas with two cell lines and all but one hypodiploid tumor. Most tumors with an aggressive clinical course were either aneuploid or diploid but with a high percentage of proliferating cells.     

Plasma fibronectin concentrations in healthy and septic infants

The concentration of plasma fibronectin was determined by Laurell's electroimmunoasay [15] in 75 preterm or term newborns within the first 2 days of life, in 97 healthy infants aged from 3 days to 12 months, in 40 septic infants and in 38 healthy adult subjects. The mean fibronectin concentration in citrated plasma of normal adults was 318±84 ml/l. Healthy eutrophic term newborns 1–2 days old had approximately one-third of the fibronectin concentration of adults. There was no significant difference in the values between healthy term and eutrophic preterm newborns or between eutrophic and hypotrophic newborns. The plasma fibronectin increased strongly over the 1st month of life. No significant difference was observed between fibronectin levels in infant boys and girls. The values in septic newborns and septic older infants were significantly lower when compared with those of age-matched healthy controls. It is speculated that this deficiency, because of linkage to fibrin in disseminated intravascular coagulation or due to increased utilisation as a non-specific opsonin and sequestration at sites of tissue injury, may contribute to organ failure in septicaemia.Abbreviations SB surface binding - DIC disseminated intravascular coagulation